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1. Chronic kidney disease: detect, diagnose, disclose—a UK primary care perspective of barriers and enablers to effective kidney care

Author

Stuart Stewart, Philip A. Kalra, Tom Blakeman, Evangelos Kontopantelis, Howard Cranmer-Gordon, and Smeeta Sinha

Subjects
Chronic kidney disease, Primary care, Detection, Screening, Population health, COVID-19, Medicine
Abstract

Abstract Chronic kidney disease (CKD) is a global public health problem with major human and economic consequences. Despite advances in clinical guidelines, classification systems and evidence-based treatments, CKD remains underdiagnosed and undertreated and is predicted to be the fifth leading cause of death globally by 2040. This review aims to identify barriers and enablers to the effective detection, diagnosis, disclosure and management of CKD since the introduction of the Kidney Disease Outcomes Quality Initiative (KDOQI) classification in 2002, advocating for a renewed approach in response to updated Kidney Disease: Improving Global Outcomes (KDIGO) 2024 clinical guidelines. The last two decades of improvements in CKD care in the UK are underpinned by international adoption of the KDIGO classification system, mixed adoption of evidence-based treatments and research informed clinical guidelines and policy. Interpretation of evidence within clinical and academic communities has stimulated significant debate of how best to implement such evidence which has frequently fuelled and frustratingly forestalled progress in CKD care. Key enablers of effective CKD care include clinical classification systems (KDIGO), evidence-based treatments, electronic health record tools, financially incentivised care, medical education and policy changes. Barriers to effective CKD care are extensive; key barriers include clinician concerns regarding overdiagnosis, a lack of financially incentivised care in primary care, complex clinical guidelines, managing CKD in the context of multimorbidity, bureaucratic burden in primary care, underutilisation of sodium-glucose co-transporter-2 inhibitor (SGLT2i) medications, insufficient medical education in CKD, and most recently – a sustained disruption to routine CKD care during and after the COVID-19 pandemic. Future CKD care in UK primary care must be informed by lessons of the last two decades. Making step change, over incremental improvements in CKD care at scale requires a renewed approach that addresses key barriers to detection, diagnosis, disclosure and management across traditional boundaries of healthcare, social care, and public health. Improved coding accuracy in primary care, increased use of SGLT2i medications, and risk-based care offer promising, cost-effective avenues to improve patient and population-level kidney health. Financial incentives generally improve achievement of care quality indicators – a review of financial and non-financial incentives in CKD care is urgently needed.

Published
2024
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2. Membranoproliferative Glomerulonephritis over 20 Years at a Tertiary Referral Center in the UK

Author

Hannah O'Keeffe, Joshua Storrar, Chethana Ramakrishna, Sara Metaoy, Constantina Chrysochou, Rajkumar Chinnadurai, Philip A. Kalra, and Smeeta Sinha

Subjects
glomerular diseases, glomerulonephritis, membranoproliferative glomerulonephritis, pathology, rare disease, renal biopsy, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction: Membranoproliferative glomerulonephritis (MPGN) is a pattern of injury seen on kidney biopsy, with various underlying etiologies. The component types, including complement-mediated MPGN, are relatively rare. This study presents longitudinal real-world data over 20 years in a tertiary renal center in the UK. Methods: All patients with an MPGN pattern on kidney biopsy between 2000 and 2020 were identified. After applying exclusion criteria, 38 patients remained. Data including patient demographics, details of the renal histology from the kidney biopsy, baseline laboratory results, treatments received, and clinical outcomes including renal replacement therapy and death were collected from the organization’s electronic patient record. Results: Twenty-eight of the cohort had immune complex-mediated MPGN, and 10 had complement-mediated MPGN (8 with C3 glomerulonephritis and 2 with dense deposit disease). Median follow-up was 72 months. Median age was 61 years. Overall, 60.5% were female, and 92.1% white. At presentation, median eGFR was 31.5 mL/min/1.73 m2 and uPCR 394 mg/mmol. Here, 78.9% received renin-angiotensin-aldosterone system inhibitors and 71.1% received any immunosuppression. In total, 47.4% progressed to ESKD and 50% died during follow-up. Conclusions: The study found an older patient population than typically reported. Poor outcomes were observed in the overall cohort with progression to ESKD and mortality both at almost 50%. This may be influenced by the older patient population. Individualized management of patients with an MPGN biopsy finding is paramount, with comprehensive evaluation for triggers and complement abnormalities. Going forward, registry enrolment and collaborative studies may enhance knowledge and outcomes.

Published
2024
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3. Hexasodium fytate for the treatment of calciphylaxis: a randomised, double-blind, phase 3, placebo-controlled trial with an open-label extensionResearch in context

Author

Smeeta Sinha, Sagar U. Nigwekar, Vincent Brandenburg, Lisa J. Gould, Thomas E. Serena, Sharon M. Moe, George R. Aronoff, Dinesh K. Chatoth, Jeffrey L. Hymes, Kevin J. Carroll, Gabriela Alperovich, Laurence H. Keller, Joan Perelló, Alex Gold, and Glenn M. Chertow

Subjects
Calciphylaxis, Calcific uraemic arteriolopathy, Dialysis, SNF472, Hexasodium fytate, Calcification, Medicine (General), R5-920
Abstract

Summary: Background: In the CALCIPHYX trial, we investigated hexasodium fytate, an inhibitor of vascular calcification, for the treatment of calcific uraemic arteriolopathy (calciphylaxis), a rare condition characterised by painful, non-healing skin lesions. Methods: In this international, phase 3, randomised, double-blind, placebo-controlled trial, adults with an ulcerated calciphylaxis lesion and pain visual analogue scale (VAS) score ≥50/100 were randomised 1:1 to hexasodium fytate 7 mg/kg or placebo intravenously during maintenance haemodialysis. Primary efficacy outcomes were an 8-item modification of the Bates-Jensen Wound Assessment Tool (BWAT-CUA) and Pain VAS in the intention-to-treat population. ClinicalTrials.gov number: NCT04195906. Findings: Overall, 34/37 patients randomised to hexasodium fytate and 26/34 patients randomised to placebo completed the 12-week randomised treatment period. At Week 12, both groups (hexasodium fytate versus placebo) showed similar improvements in BWAT-CUA (mean [standard deviation (SD)], −5.3 [5.2] versus −6.0 [6.2]; least squares mean difference, 0.3 [96% confidence interval (CI): −2.5, 3.0]; p = 0.88) and Pain VAS (mean [SD], −19.5 [26.9] versus −32.2 [38.5]; least squares mean difference, 11.5 [96% CI: −4.8, 27.8]; p = 0.15). One patient randomised to placebo briefly received hexasodium fytate in error. Serious adverse events through Week 12 included: calciphylaxis-related events leading to hospitalisation (2/38 [5%] versus 11/33 [33%]) and death (1/38 [3%] versus 5/33 [15%]). During the subsequent 12 weeks of open-label hexasodium fytate and 4 weeks of follow-up, there were no additional calciphylaxis-related events leading to hospitalisation. Over the course of the entire trial, deaths were 2/38 [5%] for the hexasodium fytate group and 7/33 [21%] for the placebo group. Interpretation: In patients with calciphylaxis, BWAT-CUA and Pain VAS improved similarly in hexasodium fytate- and placebo-treated patients; over the course of the entire trial, there were fewer deaths and calciphylaxis-related events leading to hospitalisation in the hexasodium fytate group. Funding: Funded by Sanifit, a CSL Vifor company.

Published
2024
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4. The epidemiology of primary FSGS including cluster analysis over a 20-year period

Author

Thomas McDonnell, Joshua Storrar, Rajkumar Chinnadurai, Calvin Heal, Constantina Chrysochou, James Ritchie, Francesco Rainone, Dimitrios Poulikakos, Philip Kalra, and Smeeta Sinha

Subjects
Cluster analysis, Epidemiology, FSGS, Immunosuppression, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Introduction Focal segmental glomerulosclerosis (FSGS) is one of the leading causes of nephrotic syndrome in adults. This epidemiological study describes a renal centre’s 20-year experience of primary FSGS. Methods Patients were identified with a diagnosis of primary FSGS after exclusion of known secondary causes. In this retrospective observational study, data was collected for baseline demographics, immunosuppression and outcomes. A two-step cluster analysis was used to identify natural groupings within the dataset. Results The total cohort was made up of 87 patients. Those who received immunosuppression had lower median serum albumin than those who did not- 23g/L vs 40g/L (p 30g/L. This group may still have immune mediated disease and thus could potentially benefit from immunosuppression. Trial registration This study protocol was reviewed and approved by the ‘Research and Innovation committee of the Northern Care Alliance NHS Group’, study approval number (Ref: ID 22HIP54).

Published
2023
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5. Clinical Phenotype and Outcomes of Indo-Asian Patients with ANCA-Associated Glomerulonephritis in the North West, UK

Author

Lauren Floyd, Joshua Storrar, Sanjeev Pramanik, Adam D. Morris, Smeeta Sinha, Silke R. Brix, Philip A. Kalra, and Ajay P. Dhaygude

Subjects
ANCA, vasculitis, glomerulonephritis, ethnicity, epidemiology, Internal medicine, RC31-1245
Abstract

ANCA-associated vasculitides (AAV) are rare, autoimmune conditions associated with end-stage kidney disease (ESKD) and mortality. Data have predominately been from White populations of European ancestry although geographical differences are well documented. Few studies have looked at the incidence, phenotype and clinical outcomes of ethnic minority patients, in particular Indo-Asian populations. A two-center, retrospective cohort study was conducted of patients with ANCA-associated glomerulonephritis (AAGN), self-identifying as Indo-Asian in the North West, UK between 2009 and 2023. A control group of White patients was identified from the same databases and recruited consecutively in relation to the original cohort of Indo-Asian patients. A total of 66 patients were included, 24 patients of Indo-Asian ethnicity and a control cohort of 42 patients of White ethnicity. Indo-Asian patients had a lower median age at diagnosis (53.0 vs. 57.5 years, p = 0.15) and there was an increased prevalence of diabetes mellitus (33.3% vs. 4.8%, p = 0.002) and a higher incidence of previous TB exposure (12.5% vs. 0%, p = 0.019). Outcomes including relapse, ESKD and mortality were similar. We demonstrated an increased crude incidence of AAGN in Indo-Asian patients in the UK compared to similar epidemiological studies. Consideration needs to be given to epidemiological and genetic research, achieved by collaboration and broader recruitment in clinical trials.

Published
2023
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6. Obesity and chronic kidney disease: A current review

Author

Saira Nawaz, Rajkumar Chinnadurai, Saif Al‐Chalabi, Philip Evans, Philip A. Kalra, Akheel A. Syed, and Smeeta Sinha

Subjects
chronic kidney disease, dialysis, obesity, transplantation, Internal medicine, RC31-1245
Abstract

Abstract Background Obesity poses significant challenges to healthcare globally, particularly through its bi‐directional relationship with co‐morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity‐related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon‐like peptide‐1 receptor agonists and sodium–glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi‐faceted actions on major outcomes.

Published
2023
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7. Improving outpatient clinic experience: the future of chronic kidney disease care and associated multimorbidity

Author

Smeeta Sinha, Dimitrios Poulikakos, Darren Green, Natalie Garratt, Philip A Kalra, James Ritchie, Saif Al-Chalabi, Helen Alderson, and Schanhave Santhirasekaran

Subjects
Medicine (General), R5-920
Abstract

Background Chronic kidney disease (CKD) is estimated to affect more than 2.5 million adults in England, and this is expected to rise to 4.2 million by 2036 (1). Population-level digital healthcare systems have the potential to enable earlier detection of CKD providing an opportunity to introduce interventions that attenuate progression and reduce the risk of end-stage kidney disease (ESKD) and cardiovascular diseases (CVD). Services that can support patients with CKD, CVD, and diabetes mellitus (DM) have the potential to reduce fragmented clinical care and optimise pharmaceutical management.Methods and results The Salford renal service has established an outpatient improvement programme which aims to address these issues via two projects. Firstly, the development of a CKD dashboard that can stratify patients by their kidney failure risk equation (KFRE) risk. High-risk patients would be invited to attend an outpatient clinic if appropriate. Specialist advice and guidance would be offered to primary care providers looking after patients with medium risk. Patients with lower risk would continue with standard care via their primary care provider unless there was another indication for a nephrology referral. The CKD dashboard identified 11546 patients (4.4% of the total adult population in Salford) with T2DM and CKD. The second project is the establishment of the Metabolic CardioRenal (MRC) clinic. It provided care for 209 patients in the first 8 months of its establishment with a total of 450 patient visits. Initial analysis showed clustering of cardiorenal metabolic diseases with 85% having CKD stages 3 and 4 and 73.2% having DM. In addition, patients had a significant burden of CVD with 50.2% having hypertension and 47.8% having heart failure.Conclusion There is a pressing need to create new outpatient models of care to tackle the rising epidemic of cardio-renal metabolic diseases. This model of service has potential benefits at both organisational and patient levels including improving patient management via risk stratification, increased care capacity and reduction of variation of care. Patients will benefit from earlier intervention, appropriate referral for care, reduction in CKD-related complications, and reduction in hospital visits and cardiovascular events. In addition, this combined digital and patient-facing model of care will allow rapid translation of advances in cardio-renal metabolic diseases into clinical practice.

Published
2023
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8. Safely reducing haemodialysis frequency during the COVID-19 pandemic

Author

Michelle Da Silva Lodge, Thilini Abeygunaratne, Helen Alderson, Ibrahim Ali, Nina Brown, Constantina Chrysochou, Rosie Donne, Ibi Erekosima, Philip Evans, Emma Flanagan, Simon Gray, Darren Green, Janet Hegarty, Audrey Hyde, Philip A. Kalra, Elizabeth Lamerton, David Lewis, Rachel Middleton, David New, Robert Nipah, Donal O’Donoghue, Edmond O’Riordan, Dimitrios Poulikakos, Francesco Rainone, Maharajan Raman, James Ritchie, Smeeta Sinha, Grahame Wood, and J. Tollitt

Subjects
COVID-19, Haemodialysis, Coronavirus, Mortality, Twice weekly, SARS-CoV-2, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Patients undergoing haemodialysis (HD) are at higher risk of developing worse outcomes if they contract COVID-19. In our renal service we reduced HD frequency from thrice to twice-weekly in selected patients with the primary aim of reducing COVID 19 exposure and transmission between HD patients. Methods Dialysis unit nephrologists identified 166 suitable patients (38.4% of our HD population) to temporarily convert to twice-weekly haemodialysis immediately prior to the peak of the COVID-19 pandemic in our area. Changes in pre-dialysis weight, systolic blood pressure (SBP) and biochemistry were recorded weekly throughout the 4-week project. Hyperkalaemic patients (serum potassium > 6.0 mmol/L) were treated with a potassium binder, sodium bicarbonate and received responsive dietary advice. Results There were 12 deaths (5 due to COVID-19) in the HD population, 6 of which were in the twice weekly HD group; no deaths were definitively associated with change of dialysis protocol. A further 19 patients were either hospitalised and/or developed COVID-19 and thus transferred back to thrice weekly dialysis as per protocol. 113 (68.1%) were still receiving twice-weekly HD by the end of the 4-week project. Indications for transfer back to thrice weekly were; fluid overload (19), persistent hyperkalaemia (4), patient request (4) and compliance (1). There were statistically significant increases in SBP and pre-dialysis potassium during the project. Conclusions Short term conversion of a large but selected HD population to twice-weekly dialysis sessions was possible and safe. This approach could help mitigate COVID-19 transmission amongst dialysis patients in centres with similar organisational pressures.

Published
2020
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9. Pain management in patients with end-stage renal disease and calciphylaxis- a survey of clinical practices among physicians

Author

Rajkumar Chinnadurai, Smeeta Sinha, Aoife C Lowney, and Mary Miller

Subjects
Calciphylaxis, Guidelines, Opioids, Pain management, Palliative care, Survey, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Background Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline. Methods An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options. Results One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time. Conclusion There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.

Published
2020
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10. A low rate of end-stage kidney disease in membranous nephropathy: A single centre study over 2 decades

Author

Joshua Storrar, Tarra Gill-Taylor, Rajkumar Chinnadurai, Constantina Chrysochou, Dimitrios Poulikakos, Francesco Rainone, James Ritchie, Elizabeth Lamerton, Philip A. Kalra, and Smeeta Sinha

Subjects
Medicine, Science
Abstract

Introduction Membranous nephropathy is the commonest cause of nephrotic syndrome in non-diabetic Caucasian adults over the age of 40 years. Primary membranous nephropathy is limited to the kidneys. Clinical management aims to induce remission, either spontaneously with supportive care, or with immunosuppression. Here, we describe the natural history of this condition in a large tertiary centre in the UK. Methods 178 patients with primary membranous nephropathy were identified over 2 decades. We collected data on demographics, baseline laboratory values, treatment received and outcomes including progression to renal replacement therapy and death. Analysis was performed on the whole cohort and specific subgroups. Univariate and multivariate Cox regression was also performed. Results Median age was 58.3 years with 63.5% male. Median baseline creatinine was 90μmol/L and urine protein-creatinine ratio 664g/mol. Remission (partial or complete) was achieved in 134 (75.3%), either spontaneous in 60 (33.7%) or after treatment with immunosuppression in 74 (41.6%), and of these 57 (42.5%) relapsed. Progression to renal replacement therapy was seen in 10.1% (much lower than classically reported) with mortality in 29.8%. Amongst the whole cohort, those who went into remission had improved outcomes compared to those who did not go into remission (less progression to renal replacement therapy [4.5% vs 28%] and death [20.1% vs 67%]. Those classified as high-risk (based on parameters including eGFR, proteinuria, serum albumin, PLA2R antibody level, rate of renal function decline) also had worse outcomes than those at low-risk (mortality seen in 52.6% vs 10.8%, pConclusion We provide a comprehensive epidemiologic analysis of primary membranous nephropathy at a large tertiary UK centre. Only 10.1% progressed to renal replacement therapy. For novelty, the KDIGO risk classification was linked to outcomes, highlighting the utility of this classification system for identifying patients most likely to progress.

Published
2022

11. The epidemiology and evolution of IgA nephropathy over two decades: A single centre experience.

Author

Joshua Storrar, Rajkumar Chinnadurai, Smeeta Sinha, and Philip A Kalra

Subjects
Medicine, Science
Abstract

Background and objectivesIgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, with an incidence of 2.5 per 100,000 population per year. The 10-year risk of progression to end stage kidney disease (ESKD) or halving of eGFR is 26%. Here we aimed to collect a comprehensive dataset of IgAN patients at our centre over 2 decades to provide real world data, describe outcomes and determine the effects of immunosuppression use.Design, setting, participants and measurementsAll patients diagnosed with biopsy-proven IgAN at our centre over 2 decades were identified. After exclusions, the total cohort size was 401. Data relating to (i) baseline demographics, (ii) laboratory and urine results, (iii) histological data, and (iv) outcomes of initiation of renal replacement therapy (RRT) and mortality were collected.ResultsThe median age was 45.0 years, with 69.6% male and 57.6% hypertensive; 20.4% received immunosuppression, 29.7% progressed to RRT and 19.7% died, over a median follow up period of 51 months. Baseline eGFR was 46.7ml/min/1.73m2 and baseline uPCR was 183mg/mmol. Median rate of eGFR decline was -1.31ml/min/1.73m2/year. Those with a higher MEST-C score had worse outcomes. Immunosuppression use was associated with an increased rate of improvement in proteinuria, but not with a reduction in RRT or mortality. Factors favouring improved outcomes with immunosuppression use included female gender; lower age, blood pressure and T-score; higher eGFR; and ACEi/ARB use.ConclusionsA variety of clinical and histological factors are important in determining risk of progression in IgAN. Therapeutic interventions, particularly use of immunosuppression, should be individualised and guided by these factors.

Published
2022
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12. Presentation of laboratory test results in patient portals: influence of interface design on risk interpretation and visual search behaviour

Author

Paolo Fraccaro, Markel Vigo, Panagiotis Balatsoukas, Sabine N. van der Veer, Lamiece Hassan, Richard Williams, Grahame Wood, Smeeta Sinha, Iain Buchan, and Niels Peek

Subjects
User-computer interface [MeSH], Computers/utilization [MeSH], Decision making [MeSH], Personal health record [MeSH], Patient access to records [MeSH], Patient portals, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

Abstract Background Patient portals are considered valuable instruments for self-management of long term conditions, however, there are concerns over how patients might interpret and act on the clinical information they access. We hypothesized that visual cues improve patients’ abilities to correctly interpret laboratory test results presented through patient portals. We also assessed, by applying eye-tracking methods, the relationship between risk interpretation and visual search behaviour. Methods We conducted a controlled study with 20 kidney transplant patients. Participants viewed three different graphical presentations in each of low, medium, and high risk clinical scenarios composed of results for 28 laboratory tests. After viewing each clinical scenario, patients were asked how they would have acted in real life if the results were their own, as a proxy of their risk interpretation. They could choose between: 1) Calling their doctor immediately (high interpreted risk); 2) Trying to arrange an appointment within the next 4 weeks (medium interpreted risk); 3) Waiting for the next appointment in 3 months (low interpreted risk). For each presentation, we assessed accuracy of patients’ risk interpretation, and employed eye tracking to assess and compare visual search behaviour. Results Misinterpretation of risk was common, with 65% of participants underestimating the need for action across all presentations at least once. Participants found it particularly difficult to interpret medium risk clinical scenarios. Participants who consistently understood when action was needed showed a higher visual search efficiency, suggesting a better strategy to cope with information overload that helped them to focus on the laboratory tests most relevant to their condition. Conclusions This study confirms patients’ difficulties in interpreting laboratories test results, with many patients underestimating the need for action, even when abnormal values were highlighted or grouped together. Our findings raise patient safety concerns and may limit the potential of patient portals to actively involve patients in their own healthcare.

Published
2018
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13. The importance of acute kidney injury in suspected community acquired infection.

Author

James Tollitt, Nicola Bennett, Denise Darby, Emma Flanagan, Paul Chadwick, Smeeta Sinha, Philip A Kalra, James Ritchie, and Dimitrios Poulikakos

Subjects
Medicine, Science
Abstract

BackgroundMost sepsis and acute kidney injury (AKI) cases are community acquired (CA). The aim of this study was to evaluate the characteristics of suspected community acquired infection (sCA-I) and CA-AKI and their impact upon patient outcomes.MethodsAll adult creatinine blood tests from non-elective, non-dialysis attendances to a single centre over a 29-month period were analysed retrospectively. We defined sCA-I and CA-AKI cases as antibiotic prescription and AKI alert within 48 hours of attendance respectively. Binary logistic regression models were created to determine associations with 30-day mortality, intensive care unit (ICU) admission and length of stay (LOS) dichotomised at median.ResultsOf 61,471 attendances 28.1% and 5.7% suffered sCA-I or CA-AKI in isolation respectively, 3.4% suffered both. sCA-I was present in 58.8% of CA-AKI cases and CA-AKI was present in 11.9% of CA-I cases. The combination of sCA-I and CA-AKI was associated with a higher risk for all outcomes compared to sCA-I or CA-AKI in isolation. The 30-day mortality was 8.1%, 11.8% and 26.2% in patients with sCA-I, CA-AKI and when sCA-I and CA-AKI occurred in combination respectively. The adjusted odds ratios (OR) and 95% confidence intervals (CI) for 30-day mortality, ICU admission and LOS for sCA-I combined with CA-AKI stage 1 were OR 6.09:CI: 5.21-7.12, OR 12.52 CI: 10.54-14.88 and OR 8.97 CI: 7.62-10.56, respectively, and for combined sCA-I and CA-AKI stage 3 were OR 9.23 CI: 6.91-12.33, OR 29.26 CI: 22.46-38.18 and OR 9.48 CI: 6.82-13.18 respectively.ConclusionThe combination of sCA-I and CA-AKI is associated with worse outcomes.

Published
2019
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14. Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis

Author

Lisa J. Gould, Thomas E. Serena, and Smeeta Sinha

Subjects
calciphylaxis, scale, rating, wound, healing, Medicine (General), R5-920
Abstract

Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe form of vascular calcification with no approved therapies. A standardized wound assessment tool is needed to evaluate changes in calciphylaxis wounds over time. A prospective, single-arm study of 14 patients with calciphylaxis reported improvement for the primary endpoint of wound healing using the 13-item Bates-Jensen Wound Assessment Tool (BWAT), although that tool was developed for assessment of pressure ulcers. This report describes development of BWAT-CUA, an 8-item modification of BWAT focusing on prototypical features of calciphylaxis lesions. The BWAT-CUA has a range of 8 (best) to 40 (worst) and was used ad hoc to analyze BWAT data collected in the prospective study. Using BWAT-CUA, relative improvement in calciphylaxis wounds was 30% overall (from 21.2 to 14.9; p = 0.0016) and 34% in the subset of 12 patients with ulceration at baseline (from 23.3 to 15.3; p = 0.0002). BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice.

Published
2021
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15. FTI-277 inhibits smooth muscle cell calcification by up-regulating PI3K/Akt signaling and inhibiting apoptosis.

Author

Arvind Ponnusamy, Smeeta Sinha, Gareth D Hyde, Samantha J Borland, Rebecca F Taylor, Emma Pond, Heather J Eyre, Colette A Inkson, Andrew Gilmore, Nick Ashton, Philip A Kalra, and Ann E Canfield

Subjects
Medicine, Science
Abstract

BackgroundVascular calcification is associated with increased cardiovascular morbidity and mortality in patients with atherosclerosis, diabetes and chronic kidney disease. However, no viable treatments for this condition have been identified. This study aimed to determine whether farnesyl transferase inhibitors (FTIs) can reduce vascular calcification and the mechanism by which this reduction occurs.ResultsWe demonstrate that FTI-277 significantly inhibits phosphate-induced mineral deposition by vascular smooth muscle cells (VSMC) in vitro, prevents VSMC osteogenic differentiation, and increases mRNA expression of matrix Gla protein (MGP), an inhibitor of mineralization. FTI-277 increases Akt signaling in VSMC in short-term serum-stimulation assays and in long-term mineralization assays. In contrast, manumycin A has no effect on Akt signaling or mineralization. Co-incubation of VSMC with FTI-277 and SH6 (an Akt inhibitor) significantly reduces the inhibitory effect of FTI-277 on mineralization, demonstrating that FTI-277 inhibits calcification by activating Akt signaling. Over-expression of the constitutively active p110 sub-unit of PI3K in VSMC using adenovirus activates Akt, inhibits mineralization, suppresses VSMC differentiation and significantly enhances MGP mRNA expression. FTI-277 also inhibits phosphate-induced activation of caspase 3 and apoptosis of VSMC, and these effects are negated by co-incubation with SH6. Finally, using an ex vivo model of vascular calcification, we demonstrate that FTI-277 inhibits high phosphate-induced mineralization in aortic rings derived from rats with end-stage renal failure.ConclusionsTogether, these results demonstrate that FTI-277 inhibits VSMC mineral deposition by up-regulating PI3K/Akt signaling and preventing apoptosis, suggesting that targeting farnesylation, or Akt specifically, may have therapeutic potential for the prevention of vascular calcification.

Published
2018
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18. Clinical and histopathologic predictors of recurrent glomerulonephritis after kidney transplantation

Author

Chukwuma A. Chukwu, Christopher Holmberg, Joshua Storrar, Rachel Middleton, Smeeta Sinha, Phillip A. Kalra, Howida Shawki, and Anirudh Rao

Subjects
Recurrent IgA nephropathy, Transplantation, Allograft loss, Graft survival, Recurrent focal segmental glomerulosclerosis, Recurrent glomerulonephritis, Kidney Transplantation
Abstract

IntroductionWe evaluated the long-term outcomes of recurrent glomerulonephritis (RGN) using clinical, histopathological, and demographic predictors.MethodsA retrospective cohort study of kidney transplant recipients (KTR) in two renal centers between 2005 and 2020. Clinical and native kidney histological data were analyzed. The risk factors and outcomes of each primary glomerulonephritis subtype were assessed using Cox methods.Result336 recipients with primary glomerulonephritis were analyzed. RGN was diagnosed in 17%, 20%, 25%, and 13% of recipients with IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN) and membranoproliferative glomerulonephritis (MPGN), respectively. Median time to recurrence was shortest in FSGS (.6 years IQR .2-2.9) and longest in MN (6.3 years IQR 3.3-8.0) whereas time to graft loss after diagnosis was shortest in MPGN (.3 years IQR .1-1.7) and longest in IgAN (2.9 year IQR 1.3-4.3). Recipients with recurrent IgAN were likely to be younger, have higher proteinuria at diagnosis, receive living donor allografts, receive cyclosporine treatment, have a history of acute rejection, and have segmental sclerosis in native glomeruli. Younger age of the donors, higher proteinuria at diagnosis, alemtuzumab, proteinuria within the first 12 months, acute rejection, low baseline eGFR, mesangial proliferation, and IgG and IgA deposits were associated with FSGS recurrence. MPGN recurrence was predicted by lower BMI at transplantation, and crescentic native disease. Death-censored graft survival at 5-, 10-, and 15-years was 83%, 51%, and 29% in the RGN group and 95%, 93%, and 84%, respectively in the non-RGN group. Over 15 years, recipients with RGN are nine times more likely than those without RGN to lose their grafts, regardless of donor type, acute rejection, and baseline eGFR. Transplant recipients of related donor allograft were not more likely to have recurrent GN than non-related donors.

Published
2023

19. COVID-19 in Patients with Glomerular Disease: Follow-Up Results from the IRoc-GN International Registry

Author

Meryl Waldman, Maria Jose Soler, Clara García-Carro, Liz Lightstone, Tabitha Turner-Stokes, Megan Griffith, Joan Torras, Laura Martinez Valenzuela, Oriol Bestard, Colin Geddes, Oliver Flossmann, Kelly L. Budge, Chiara Cantarelli, Enrico Fiaccadori, Marco Delsante, Enrique Morales, Eduardo Gutierrez, Jose A. Niño-Cruz, Armando J. Martinez-Rueda, Giorgia Comai, Claudia Bini, Gaetano La Manna, Maria F. Slon, Joaquin Manrique, Alejandro Avello, Raul Fernandez-Prado, Alberto Ortiz, Smaragdi Marinaki, Carmen Rita Martin Varas, Cristina Rabasco Ruiz, Milagros Sierra-Carpio, Rebeca García-Agudo, Gema Fernández Juárez, Alexander J. Hamilton, Annette Bruchfeld, Constantina Chrysochou, Lilian Howard, Smeeta Sinha, Tim Leach, Irene Agraz Pamplona, Umberto Maggiore, and Paolo Cravedi

Subjects
SARS-CoV-2, COVID-19, Humans, Registries, General Medicine, Acute Kidney Injury, Original Investigation, Follow-Up Studies
Abstract

Background The acute and long-term effects of severe acute respiratory syndrome coronavirus 2 infection in individuals with GN are still unclear. To address this relevant issue, we created the International Registry of COVID-19 infection in GN.Methods We collected serial information on kidney-related and -unrelated outcomes from 125 GN patients (63 hospitalized and 62 outpatients) and 83 non-GN hospitalized patients with coronavirus disease 2019 (COVID-19) and a median follow-up period of 6.4 (interquartile range 2.3–9.6) months after diagnosis. We used logistic regression for the analyses of clinical outcomes and linear mixed models for the longitudinal analyses of eGFR. All multiple regression models were adjusted for age, sex, ethnicity, and renin-angiotensin-aldosterone system inhibitor use.Results After adjustment for pre-COVID-19 eGFR and other confounders, mortality and AKI did not differ between GN patients and controls (adjusted odds ratio for AKI=1.28; 95% confidence interval [CI], 0.46 to 3.60; P=0.64). The main predictor of AKI was pre-COVID-19 eGFR (adjusted odds ratio per 1 SD unit decrease in eGFR=3.04; 95% CI, 1.76 to 5.28; PConclusions Pre-COVID-19 eGFR is the main risk factor for AKI regardless of GN diagnosis. However, GN patients are at higher risk of impaired eGFR recovery after COVID-19-associated AKI. These patients (especially those with high baseline proteinuria or a diagnosis of focal segmental glomerulosclerosis or minimal change disease) should be closely monitored not only during the acute phases of COVID-19 but also after its resolution.

Published
2022

20. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, Srinivasan Beddhu, Laith Al-Rabadi, Nikita Abraham, Amalia Caamano, Judy Carle, Victoria Gonce, Kaitlyn Staylor, Na Zhou, Shweta Bansal, Manoj Bhattarai, Kumar Sharma, Subrata Debnath, Aliseiya Garza, Chakradhar Velagapudi, Sergio Rovner, Javier Almeida, Pablo Casares, Verlaine Stewart-Ray, Rene Almaraz, Renata Dayrell, Ana Moncada, Ricardo Pulido, Roxana Rodriquez, Wasim Deeb, Kathryn DeGoursey, Rodel Gloria, Trevor Greene, Robert Miller, Edward Pereira, Miguel Roura, Debbie Domingo, Sasha Dorestin, William Hodge, Cathy Jackson, Deborah Lund, Katrina Taylor, Kenneth Boren, Brittany Cleveland, Sandra Gaiser, Mandeep Sahani, Logan Aldrich, Exodus Edmerson, Edmond Limon, Cole Valletta, Patricia Vasquez, Christopher Provenzano, Navkiranjot Brar, Heather Henderson, Bellovich Keith, Qur Khai, Quresh Khairullah, Gail Makos, Joel Topf, Sherry Gasko, Rosemarie Henschel, Kaitlin Knapp, Teresa Kozlowski, Paula LaFleur, Ashwathy Varughese, Hui Xue, Patricia Wu, Olga Arechiga, Shan Darbeau, Michael Fechter, Stephanie Martinez, Lenita Hanson, Nyla Cooper, Arelis Madera, Jay Cadorna, Rita Sheridan, Helen Sparks, Bradley Eilerman, Susanne Bodine, Wael Eid, Rebecca Flora, Amber Avery, Cashmere Hardy, Mihaela Biscoveanu, Steven Nagelberg, Tracey Cummins, Frederic Rahbari-Oskoui, Anju Oommen, Zohreh Forghani, Stacie Hitchcock, Darya Hosein, Diane Watkins, Minesh Patel, Anthony Lambert, Elizabeth Newman, Autumn Wood, Tammy Ross, Stephany Topping, Jeffrey Mulhern, Lorna Murphy, Ann Vasseur, Gregory Greenwood, Alexander Hadley, Denise Laurienti, Christopher Marshall, Nicholas McLean, Scott Satko, Brandy Caudill, Jacob Maris, Janice Rogers, Cindy Vanhoy, George Thomas, Georges Nakhoul, John O'Toole, Jonathan Taliercio, Leslie Cooperman, Marina Markovic, Barbara Tucky, Devasmita Dev, Alia Hasan, Hima Yalamanchili, Namita Jain, Lesley McNeil, Eric Wines, Jean Park, Adline Ghazi, Mia Hamm, Tejas Patel, Amy Mottl, Emily Chang, Vimal Derebail, Emmie Cole, Anne Froment, Sara Kelley, Jordan Osmond Foster, Vahid Mahabadi, Golriz Jafari, Anita Kamarzarian, Wendy Arriaga, Daisy Arteaga, Rosario Machicado, Genesis Naverrete, Prashant Kumar, Imran Nazeer, Karina Urquia, Tammi Glider, Vickie Jones, Savannah Rucker, Jennifer Wiley, Rahul Pandey, Jesus Arroyo, Harish Pariani, Mohammad Ahmad, Shahin Mozaffari, Erika Perez, Matthew Budoff, Sion Roy, Divya Birudaraju, Ahmed Ghanem, Sajad Hamal, Stephen Aronoff, Elisa Joye Petr, Richard Sachson, Jaime Wiebel, Sana Akram, Laurie Jones, Curtis Knight, Maurie Tarlac, Shahbaz Ahmed, Harold Szerlip, Akinwande Akinfolarin, Ankit Mehta, Shana Camp, Cindy Castro, Zanaida Cooper, Jessica Terry, Ahmed Awad, Bhavya Kothapalli, Ryan Lustig, Serine Alfaress, Hyder Jasim, Mary Parrigon, Dennis Karounos, Sadiq Ahmed, Maggie Berry, Ruth Oremus, Carlos Hernandez-Cassis, Elias Ugwu, Nazia Junejo, Nancy Suazo, Mark Segal, Amir Kazory, Sherry Brown, Tristan Daniels, Sofia Dayi, Renee Hogan, Kathy McCray, Jennifer Stickley, Mahboob Rahman, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Nishigandha Pradhan, Arash Rashidi, Nagaraju Sarabu, Vicki Donley, Tricia Young, Godson Oguchi, Judepatricks Onyema, Kahla Damianik, Jack Dienes, Judith Plummer-Morgan, Marilyn Roman, Mauver Skipper, Stacey-Ann Villaruel, Krystle Williams, Danny Sugimoto, Jeffrey Dugas, Ismeal Ahmed, Jamie Bhairoo, Dolores Rijos, Huzaifa Salim, Madita Gavrila, Kathryn Lafferty, Ria Rabara, Sally Ruse, Maria Weetman, James Bushnell, Albert Power, Alison Jenkins, Stefanie Jones, Amanda Scott, Cath Byrne, Mark Jesky, Alison Cowley, Emma McHaffie, Holly Waterfall, Jo Taylor, Laura Bough, Thomas Phillips, Barbara Winter-Goodwin, Sui Phin Kon, Iain MacDougall, Eirini Lioudaki, Sapna Shah, Claire Sharpe, Francisco Aguilar, Abegail Hernandez Pena, Conception Pugay, Amelia Te, Hugh Finn, Wasim Hanif, Samiul Mostafa, Alice Aitken, Katharine Draxlbauer, Evelina Grobovaite, Jennifer Kearney, Theresa McCarthy, Giorgio Gentile, Duncan Browne, Palanichamy Chellamuthu, Tabinda Dugal, Terri Chant, Laura Jones, Emily Laity, Megan Miners, James Muir, Elizabeth Swanson, Andrew Frankel, James Tomlinson, Marlon Alegata, Rashid Almasarwah, Anthoula Apostolidi, Maria Vourvou, Thomas Walters, Maarten Taal, Hari Dukka, Nitin Kolhe, Carly McDonald, Kelly White, Shiva Ugni, Smita Gunda, Rotimi Oluyombo, Vicki Brindle, Ping Coutts, Tracy Fuller, Evelyn Nadar, Suresh Ramadoss, Nichola Motherwell, Susannah Pajak, Louise Tonks, Sunil Bhandari, Richard Bodington, Adil Hazara, Dominic Fellowes, Christopher Wong, Christopher Goldsmith, Sherald Barnes, Ann Bennett, Claire Burston, Samantha Hope, Nicola Hunt, Lini Kurian, Richard Fish, Daniela Farrugia, Judy Lee, Emma Sadler, Hannah Turner, Christopher Hill, Henry Brown, Agnes Masengu, Peter Maxwell, Nina Bleakley, Hugh Murtagh, William Petchey, Vivian Yiu, Joanne Kellett, Angharad Williams, Helen Clarke, Victoria Carnall, Sarah Benyon, Caroline Blake, Stephanie Estcourt, Jane Piper, Neal Morgan, Carolyn Hutchinson, Teresa McKinley, Alastair Woodman, Judi Graham, Niall Leonard, John Smyth, Vicki Adell, Samantha Hagan, Ben Caplin, Amin Oomatia, Eleanor Damian, Toluleyi Sobande, Tim Doulton, Michael Delaney, Mahmoud Montasser, Jenny Hansen, David Loader, Angela Moon, Frances Morris, Smeeta Sinha, Chukwuma Chukwu, Amy Hudson, Diane Campbell, Melanie Kershaw, Stephanie Whittaker, Ayesha Irtiza-Ali, Farid Ghalli, Heba Nosseir, Allison Leslie, Kate Trivedi, Donald Fraser, Mohammad Alhadj Ali, Sian Griffin, Farah Latif, Justyna Witczak, Alexa Wonnacott, Lynda Jeffers, Yvette Webley, Paul Phelan, Eve Miller-Hodges, Ailsa Geddes, Margaret Glenwright, Amy Hunter, Thomas Pickett, Jim Moriarty, Linda Hill, Amanda Tyler, Waqar Ayub, Gail Evans, Sue Hewins, Davina Hewitt, Kerry Read, Samira Bell, Leanne Cosgrove, Rachel Craik, Shona Murray, Nitin Bhandary, Holly Coles, Rashmi Easow, Maya Joseph, Arif Khwaja, Yvonne Jackson, Angeline Mbuyisa, Rachel Sellars, Nihil Chitalia, Cynthia Mohandas, Anca Gherman, Charlotte Kamundi, Olumide Olufuwa, Kieran McCafferty, Adedolapo Adeleke, Cara Healy, Damini Jeyarajah, Edward Kinsella-Perks, Richard Smith, Brian Camilleri, Carol Buckman, Jenny Finch, Vanessa Rivers, Andrew Connor, Sheila Carr, Lisa Shainberg, Andrew Lewington, Richard Baker, Suzannah Dorey, Kay Tobin, Rosalyn Wheatley, Debasish Banerjee, Richard Hull, Sharirose Abat, Riny Paul, Mahzuz Karim, Zay Htet, Saad Tufail, Ravi Varma, Karen Convery, Deirdre Fottrell-Gould, Lisa Hudig, Emily Tropman, Thahir Abdul-Samad, Anne Grace, Marie Phipps, Rebecca Suckling, Subash Somalanka, Bhrigu Sood, Pauline Swift, Sarah Acheampong, Kwame Ansu, Martia Augustin, Anna Sampson, Lynn Vinall, Kim Wren, Shamila Wanninayake, Nicholas Wooding, Heather Edwards, Lydia Owen, Stephanie Bolton, Marion Carson, Michael Matthews, Nigel Brunskill, Jorge Jesus-Silva, Alex Howson, Mary Quashie-Akponeware, Hilary Tindall, Chidambaram Nethaji, Helen Eldon, Rajan Patel, Patrick Mark, Alastair Rankin, Michael Sullivan, Kirsty Forsyth, Rowan McDougall, Tanaji Dasgupta, Louisa Davies, Maggie Ryder, Philip Grimmer, Clare Macdonald, Mary Webster, Newcastle Newcastle, Timothy Ellam, Edwin Wong, Christine Meshykhi, Andrea Webster, Peter Wilson, Enric Vilar, Jocelyn Berdeprado, Eunice Doctolero, Lily Wilkinson, Frank McCarroll, Hesham Ammar, Ying Kuan, Conor Moran, Girish Shivashankar, Ryan Campbell, Deborah Glowski, Paula McDermott, Amar Ali, Zuber Patel, Christine Bond, Gillian Whalley, Haitao Zhang, Liu Yang, Lihua Zhang, Tingting Kan, Ling Zhu, Jinghong Zhao, Weiping Hou, Jing Wu, Hong Cheng, Weijing Bian, Zhirui Zhao, Fengmin Shao, Huixia Cao, Xiaojing Jiao, Peiyuan Niu, Jianying Niu, Yu Chen, Lihong Zhang, Shenglang Zhu, Haiyan Lin, Shaopeng Yao, Jiehui Chen, Ying Jiang, Ying Hu, Huaying Xiao, Fuye Yang, Xinzhou Zhang, Baochun Guo, Qiu Jin, Lixia Liu, Xiangcheng Xiao, Yanyun Xie, Ting Meng, Chuanwen Xu, Jie Huang, Yanmei Xu, Weixin Kong, Xiaoliang Wang, Qianpan Liu, Xueying Wang, Ming Gao, Xiumei Hu, Ying Lu, Li Wang, Kun Peng, Wei Wang, Qiuhong Gong, Jianfang Cai, Xiaojue Li, Xuejiao Liu, Shuhan Zhou, Hong Liu, Yao Weng, Shuai Tang, Yao Yao, Shi Zhao, Chen Cheng, Wei Wei, Na Li, Sadanah Aqashiah Mazlan, Alia Zubaidah Bahtar, Elliyyin Katiman, Noraini Othman, Lily Mushahar, Nurdiana Mazlan, Nur Sharafina Safiee, Sarasa Ramasamy, Hin Seng Wong, Hajar Ahmad Rosdi, Esther Zhao Zhi Tan, Ju Fan Tay, Kok Seng Teng, Hasnah Yahaya, Wen Jiun Liu, Lik Wee Ee, Kenneth Kay Leong Khoo, Yuana Mohd Yusoff, Fariz Safhan Mohamad Nor, Mohd Kamil Ahmad, Mohd Ramli Seman, Clare Hui Hong Tan, Laura Lui Sian Ngu, Jaime Yoke May Chan, Javelin Peji, Chek Loong Loh, Yee Yan Lee, Sridhar Ramanaidu, Kah Mean Thong, Yik Hong Wong, Suria Junus, Chen Hua Ching, Mohammad Faisal Asmee, Ku Ruziana Ku Md Razi, Chun Leong Low, Christopher Sze Bing Sim, Zhang Duan Tham, Noor Kamila Abdullah, Tai Meng Chen, Yong Chieh Chan, Eason Chang, Huan Yean Kang, Kai Quan Lee, Sue Ann Lee, Aik Kheng Lee, Jeevika Vinathan, Rizna Abdul Cader, Ruslinda Mustafar, Lydia Kamaruzaman, Rozita Mohd, Rahimah Ismail, Chong Men Leong, Chee Koon Low, Liang Wei Wong, Norlezah Adnan, Sabariah Ibrahim, Mohamad Zaimi Abdul Wahab, Sunita Bavanandan, Yik Shen Lim, Wan Hazlina Wan Mohamad, Siti Munirah Jaafar, Nur Ashykeen Mohd Fauzi, Aziee Sudin, Soo Kun Lim, Chye Chung Gan, Albert Hing, Wan Ahmad Faizal Alaidin Razali, Yew Fong Liew, Chelsia Bao Tyng Chan, Mei Chih Cheng, Yu Chen Ong, Loke Meng Ong, Farah Amalina Mohamed Affandi, Korina Rahmat, Ban Chai Peng, Masayu Amat, Nuzaimin Hadafi Ahmad, Doo Yee Mah, Yi Loon Tye, Zaid Azhari, Siti Nabilah Mohamad Zaini, Mohd Aidil Musa, Norazinizah Ahmad Miswan, Rafizanur Ramli, Nor Aziah Ahmad, Bak Leong Goh, Nurul Izah Ahmad, Fairol Huda Ibrahim, Tze Jian Ng, Malini Shanmuganathan, Li Lian Tay, Zaiha Harun, Salmi Ramli, Nurul 'Ain Yusof, Rossenizal Abd Rahman, Muhammad Iqbal Abdul Hafidz, Nur Hidayati Mohd Sharif, Irda Yasmoon Awang, Eitaro Nakashima, Rui Imamine, Makiko Minatoguchi, Yukari Miura, Miduki Nakaoka, Yoshiki Suzuki, Hitomi Yoshikawa, Koki Shin, Kanae Fujita, Misuzu Iwasa, Haruka Sasajima, Airi Sato, Yoshiyuki Hamamoto, Yuki Fujita, Takuya Haraguchi, Takanori Hyo, Kiyohiro Izumi, Toshiyuki Komiya, Sodai Kubota, Takeshi Kurose, Hitoshi Kuwata, Susumu Nakatani, Kaori Oishi, Saki Okamoto, Kaori Okamura, Jun Takeoka, Nagaaki Tanaka, Katsuya Tanigaki, Naohiro Toda, Koin Watanabe, Hiromi Komori, Rika Kumuji, Asako Takesada, Aya Tanaka, Shoichi Maruyama, Tomonori Hasegawa, Akiko Ishiguro, Takuji Ishimoto, Kazuhiro Ito, Yutaka Kamimura, Noritoshi Kato, Sawako Kato, Hiroshi Kojima, Tomoki Kosugi, Kayaho Maeda, Masasi Mizuno, Shoji Saito, Hitomi Sato, Yuka Sato, Yasuhiro Suzuki, Akihito Tanaka, Yoshinari Yasuda, Fujiko Hasegawa, Maiko Hayashi, Shizuka Higashi, Kaho Shimamura, Momoko Sumi, Kazuki Tajima, Chimaki Unekawa, Kana Wakayama, Yukiko Wakita, Takatoshi Otani, Ayako Imai, Sayaka Kawashima, Eri Kogure, Tomoe Sato, Misato Takezawa, Shinya Yoshida, Hideo Araki, Yuko 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Reina Umeno, Yoshihisa Wada, Toshiya Yamamoto, Yu Yamanouchi, Masumi Abe, Yoko Inukai, Wataru Ogawa, Shunichiro Asahara, Hideki Fujii, Shunsuke Goto, Yushi Hirota, Tetsuya Hosooka, Keiji Kono, Shinichi Nishi, Yuko Okada, Kazuhiko Sakaguchi, Kenji Sugawara, Michiko Takahashi, Tomoko Takai, Yoshikazu Tamori, Kentaro Watanabe, Miyu Kitajima, Misaki Nishi, Junko Wada, Yasuhiko Ito, Hideki Kamiya, Akimasa Asai, Nao Asai, Saeko Asano, Shogo Banno, Yohei Ejima, Hanako Hase, Tomohide Hayami, Tatsuhito Himeno, Takahiro Ishikawa, Mayumi Ito, Shiho Iwagaitsu, Rina Kasagi, Yoshiro Kato, Makoto Kato, Koichi Kato, Takayuki Katsuno, Miyuka Kawai, Hiroshi Kinashi, Masaki Kondo, Masako Koshino, Naoya Matsuoka, Yoshiaki Morishita, Mikio Motegi, Jiro Nakamura, Hiromi Shimoda, Hirokazu Sugiyama, Shin Tsunekawa, Makoto Yamaguchi, Kazuyo Takahashi, Hirotaka Watada, Takashi Funayama, Yasuhiko Furukawa, Tomohito Gohda, Hiromasa Goto, Hideyoshi Kaga, Yasuhiko Kanaguchi, Akio Kanazawa, Kayo Kaneko, Toshiki 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Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, 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Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)

Published
2023

21. Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial

Author

Hiddo J L Heerspink, Jai Radhakrishnan, Charles E Alpers, Jonathan Barratt, Stewart Bieler, Ulysses Diva, Jula Inrig, Radko Komers, Alex Mercer, Irene L Noronha, Michelle N Rheault, William Rote, Brad Rovin, Howard Trachtman, Hernán Trimarchi, Muh Geot Wong, Vlado Perkovic, Eric Alarmartine, Dong Wan Chae, Lucia Del Vecchio, Jurgen Floege, Shang-Jyh Hwang, Bojan Jelakovic, Bart Maes, Robert Malecki, Marius Miglinas, Fernando Eduardo Barbosa Nolasco, Manual Praga, Kannaiyan Rabindranath, Mai Rosenberg, Sydney Chi Wai Tang, Vladmir Tesar, Bhadran Bose, Muralikrishna Gangadharan, Stephen McDonald, Chen Peh, Sadia Jahan, Chii Yeap, Philip Clayton, Georgina Irish, Nikhil Thyagarajan, Peter Hollett, Rathika Krishnasamy, Robert Carroll, Shilpanjali Jesudason, Susan Crail, Toby Coates, Jane Waugh, Euan Noble, Kumaradevan Mahadevan, Victoria Campbell, Tania Salehi, Wai Lim, Neil Boudville, Aron Chakera, Doris Chan, Anoushka Krishnan, Yusuf Eqbal, Alastair Gillies, Eswari Vilayur, Thida Maung Maung Myint, Nicholas Gray, Melissa Cheetham, Carol Pollock, Bruce Cooper, Amanda Mather, Sarah Roxburgh, Yvonne Shen, Stefanie Stangenberg, Amanda Siriwardana, Emma O'Lone, Susan Wan, Brendon Neuen, Jeffrey Tsun Kit Ha, Dana Kim, Lauren Heath, Arunima Jain, Elaine Phua, Yan Li, Martin Gallagher, Meg Jardine, Angus Ritchie, Mona Razavian, Celine Foote, Roger Wyndham, Shaundeep Sen, Zoltan Endre, Jonathan Erlich, Mangalee Fernando, Kenneth Yong, Grant Luxton, Sradha Kotwal, Simon Roger, Vidu Wijeratne, David Packham, Ian Fraser, Bert Vandewiele, Margo Laute, Wim Lemahieu, Sofie Jamar, Sara Ombelet, Gert Meeus, Marc Decupere, Olivier Schockaert, Peter Doubel, Liesbeth Viaene, Luc Radermacher, Catherine Masset, Martial Moonen, Eric Firre, Martina Milicevic, Xavier Warling, An Vanacker, Thomas Malfait, Ivan Durlen, Ivica Horvatic, Ana Savuk, Lana Gellineo, Sandra Karanovic, Zivka Dika, Djuro Plavljanic, Ivana Mikacic, Dubravka Trajbar Kentric, Dunja Barisic, Marija Stankovic, Karolina Majstorovic Barac, Ivan Kruljac, Drasko Pavlovic, Martin Drinkovic, Ingrid Prkacin, Jerko Barbic, Zvonimir Sitas, Dunja Vujcic, Ivan Rychlik, Anna Benesova, Klara Drinovska, Karolina Kratka, Dita Maixnerova, Madis Ilmoja, Kristin Unt, Kadri Lilienthal, Asta Auerbach, Liisi Leis, Julia Piel, Annika Adoberg, Kulli Kolvald, Kristi Veermae, Kadri Telling, Elviira Seppet, Jana Uhlinova, Philippe Zaoui, Pierre-Louis Carron, Ingrid Masson, Miriana Dinic, Damien Thibaudin, Christian Broyet, Nicolas Maillard, Hesham Mohey, Christophe Mariat, Guillaume Claisse, Eric Alamartine, Bertrand Dussol, Stephane Burtey, Noemie Chiche-Jourde, Jean-Emmanuel Serre, Guillaume Jeantet, Leila Chenine, Anne Blanchard, Stephane Roueff, Eric Thervet, David Fouassier, Alexandre Buffet, Marine Livrozet, Roxane Gaisset, Alexandre Karras, Anne-Elisabeth Heng, Cyril Garrouste, Carole Philipponnet, Clementine Nicolo, Alba Atenza, Camille Lanaret, Clarisse Greze, Valentin Mayet, Clement Dumond, Yahsou Delmas, Christian Combe, Claire Rigothier, Laure Burguet, Aurore Labat, Simon Mucha, Valérie de Précigout, Thomas Weinreich, Helmut Reichel, Diliana Draganova, Lothar Wolf, Bernd Hohenstein, Sven Heinrichs, Simone Kulka, Sebahat Sat, Lea Weiland, Thilo Krueger, Gunter Wolf, Christiane Kettner, Mandy Schlosser, Johann Konstantin Herfurth, Annegret Koch, Martin Busch, Stephan Christian Werth, Martin Nitschke, Figen Cakiroglu, Franziska Sarnow, Lisa Schulz, Stefan Weiner, Nikolaus Wirtz, Eric Koester, Marcus Moeller, Eleni Stamellou, Silja Sanden, Hans Schmidt-Guertler, Wanja Bernhardt, Margret Patecki, Georg Schlieper, Kevin Schulte, Annette Girardet, Ulrich Kunzendorf, Lorraine Pui Yuen Kwan, Maggie Ming Yee Mok, Gary Chi Wang Chan, Mingyao Ma, Davina Ngoi Wah Lie, Anthony Ting Pong Chan, Cheuk Chun Szeto, Kit Chung Jack Ng, Siu Fai Cheung, Tak Tai Andrew Yue, Ka Shun Samuel Fung, Hon Tang, Ka Fai Yim, Wai Ping Law, Yick Hei Wong, Chi Kwan Darwin Lam, Sze Ho Sunny Wong, Carmelita Marcantoni, Roberta Aliotta, Francesca Deodato, Gemma Patella, Nicolino Comi, Caterina Vita, Nazareno Carullo, Davide Bolignano, Michela Musolino, Matias Trillini, Norberto Perico, Giuseppe Remuzzi, Erica Daina, Luigi Biancone, Loredana Colla, Manuel Burdese, Chiara Cogno, Elena Boaglio, Isabella Abbasciano, Carlotta Federica Zizzi, Paolo Randone, Pietro Napodano, Anna Ricchiuto, Matthias Cassia, Simone Accarino, Mario Cozzolino, Rocco Baccaro, Stefano Costanzi, Federica Di Maio, Maria Arena, Federica Urciuolo, Sara Vigano, Andrea Cavalli, Monica Limardo, Monica Bordoli, Serena Ponti, Selena Longhi, Andrea Solazzo, Francesco Giaroni, Gabriele Donati, Massimo Torreggiani, Davide Catucci, Marco Colucci, Vittoria Esposito, Ciro Esposito, Loreto Gesualdo, Flavia Capaccio, Emma Diletta Stea, Carmen Sivo, Francesca Annese, Federica Papadia, Piergiorgio Messa, Mirco Belingheri, Patrizia Passerini, Silvia Malvica, Alvita Vickiene, Urte Zakauskiene, Egle Asakiene, Inga Arune Bumblyte', Asta Stankuviene, Lina Santockiene, Ashik Hayat, Allister Williams, Peter Sizeland, Eddie Tan, Gerald Waters, Lai Wan Chan, Andrew Henderson, Angus Turnbull, Andrew McNally, Annie Reynolds, Helen Pilmore, Ian Dittmer, Paul Manley, Elizabeth Stallworthy, Tze Goh, David Semple, Michael Collins, Elizabeth Curry, Jafar Ahmed, Thu Nguyen, Agata Winiarska, Justyna Zbrzezniak, Tomasz Stompor, Magdalena Krajewska, Hanna Augustyniak-Bartosik, Dorota Zielinska, Anna Jander, Malgorzata Stanczyk, Marcin Tkaczyk, Przemyslaw Miarka, Dariusz Aksamit, Piotr Jaskowski, Wladyslaw Sulowicz, Dominik Cieniawski, Julita Gontarek-Kacprzak, Elzbieta Felicjanczuk, Norbert Kwella, Bogna Kwella, Ewa Satora, João Carlos Fernandes, Ana Marta Gomes, Marina Reis, Daniela Lopes, Catarina Almeida, Helena Sá, Ana Carolina Figueiredo, Clara Pardinhas, Edgar Almeida, Mario Raimundo, Ana Cortesão Costa, Luis Pedro Falcao Goncalves, Sara Fernandes, Sónia Silva, Catarina Teixeira, Adriana Fernandes, Fernando Nolasco, Patricia Alves, Mario Gois, Nuno Fonseca, Ana Messias, Maria Menezes, Filipa Cardoso, Helena Sousa, Joana Marques, Rui Barata, Jose Antonio Lopes, Sofia Jorge, Joana Gameiro, Jose Nuno de Almeida Agapito Fonseca, Sara Goncalves, Ana Farinha, Patricia Valerio Santos, Ana Natario, Jose Carlos de Jesus Barreto, Catarina Abrantes, Elsa Sofia Quadrado Soares, Joana de Sousa Soares Felgueiras, Liliana Cunha, Lucia Parreira, Teresa Furtado, Alvaro Vaz, Kook-Hwan Oh, Hajeong Lee, Se Joong Kim, Jong Cheol Jeong, Yeong Hoon Kim, Yunmi Kim, Hyeong Cheon Park, Hoon Young Choi, Hyung Wook Kim, Moon Hyoung Lee, Songuk Yoon, Kyu-Beck Lee, YoungYoul Hyun, Tae-Hyun Yoo, Seung Hyeok Han, Jung Tak Park, Sunggyun Kim, Young Rim Song, Jwa-Kyung Kim, Hyung-seok Lee, Narae Joo, JungEun Lee, Hye Ryoun Jang, Junseok Jeon, Wookyung Chung, HyunHee Lee, Jae Hyun Chang, Ka Yeong Chun, Ji Yong Jung, Han Ro, Aejin Kim, Sang-Kyung Jo, Jihyun Yang, Myung-Gyu Kim, SeWon Oh, Caridad Martinez Villanueva, Ana Vilar Gimeno, Gustavo Andres Useche Bonilla, Esther Tamarit, Antonio Galan Serrano, Eduardo Verde Moreno, Jose Luño Fernandez, Maria Angeles Goicoechea Diezhandino, Ursula Verdalles Guzman, Ana Perez de Jose, Alberto Ortiz Arduan, María Vanessa Pérez Gómez, Catalina Martín Cleary, Raul Fernandez Prado, Elena Goma, Jose Ballarin, Montserrat Diaz Encarnacion, Iara Da Silva Santos, Helena Marco Rusinol, Monica Furlano, Carlos Arias, Clara Barrios, Eva Rodriguez Garcia, Adriana Sierra Ochoa, Belen Vizcaino Castillo, Jonay Pantoja Perez, Mercedes Gonzalez Moya, Mari Sargsyan, Emma Calatayud Aristoy, Ana Avila Bernabeu, Leticia Perez Lluna, Tamara Malek Marin, Maria Antonia Munar Vila, Ivon Maritza Bobadilla Rico, Natalia Allende Burgos, Eduardo Gutierrez Martinez, Elena Gutierrez Solis, Angel Sevillano, Evangelina Merida Herrero, Josep Miquel Blasco Pelicano, Lida Maria Rodas Marin, Luis F Quintana, Maria Antonieta Azancot Rivero, Natalia Ramos Terrades, Clara Garcia Carro, Irene Agraz Pamplona, Mercedes Salgueira Lazo, Francisco de la Prada Alvarez, Fabiola Alonso Garcia, Wenceslao Adrian Aguilera Morales, Salia Virxinia Pol Heres, Angel Forcen, Eduardo Parra Moncasi, Cristina Medrano Villarroya, Alejandro Soria Villen, Olga Gracia Garcia, Mercedes Velo Plaza, Maria Dolores Sánchez de la Nieta, Marta Calvo Arevalo, Antolina Moreno, Secundino Cigarran Guldris, Manuel Pereira de Vicente, Bang-Gee Hsu, Chih-Hsien Wang, Cheng-Hsu Chen, Tung-Min Yu, Ming-Ju Wu, Shang-Feng Tsai, Chia-Tien Hsu, Hsien-Fu Chiu, Kang-Ju Chou, Hua-Chang Fang, Po-Tsang Lee, Hsin-Yu Chen, Chien-Liang Chen, Chien-Wei Huang, Shih-Hsiang Ou, Tzung-Yo Ho, Chih-Yang Hsu, Ming-Shan Chang, Yen-Ling Chiu, Yu-Sen Peng, Kai-Hsiang Shu, Szu-Yu Pan, Shih-Ping Hsu, Ju-Yeh Yang, Mei-Fen Pai, Po-Yu Tseng, Hon-Yen Wu, Wan-Chuan Tsai, Kuei-Ting Tung, Hung-Yuan Chen, Hung-Chun Chen, Mei-Chuan Kuo, Daw-Yang Hwang, Yi-Wen Chiu, Chi-Chih Hung, Hung-Tien Kuo, Jer-Chia Tsai, Kieran McCafferty, Suzanne Forbes, Indranil Dasgupta, Mark Thomas, Amar Mahdi, Bamidele Ajayi, Paramit Chowdhury, Theodoros Kasimatis, Dimitrios Moutzouris, Caroline Dudreuilh, Rishi Pruthi, Nick Mansfield, Gabriel Doctor, Sapna Shah, Sui Kon, Priscilla Smith, Patrick Hamilton, Durga Kanigicherla, Omar Sherin Ibrahim Ragy, Bassam Alchi, Oliver Flossmann, Farid Ghalli, Sarah Lawman, Smeeta Sinha, Constantina Chrysochou, Chukwuma Chukwu, Aine Maire De Bhailis, Saif Al Chalabi, Amy Hudson, Arun Gopu, Olivia Wickens, Joshua Storrar, Mona Wahba, Nathan Lorde, Mohammad Rony, Sian Griffin, Farah Latif, Mohammad Ali, Louise DaSilva, Jonathan Ayling-Smith, Eamon Mahdi, Lisa Willcocks, Rachel Jones, Chee Kay Cheung, Haresh Selvaskandan, Dan Pugh, Matthew Sayer, Neeraj Dhaun, Fiona Chapman, Patrick Mark, Colin Geddes, Emily McQuarrie, Rajan Patel, Laurence Solomon, Arvind Ponnusamy, Adam Morris, Pedro Okoh, Lauren Floyd, Ajay Dhaygude, Janson Leung, Christopher Goldsmith, Bhavna Pandya, Didem Tez, Ashraf Mikhail, Karen Brown, Thomas Bucknall, Mark Lambie, Roderick Comunale, Donald Brandon, Stacy Martinez, Amanda Hall, Amy Henderson, Aaron Fearday, Nicole Douthit, Brian Snow, Arnold Silva, Cathylee Sly, Christopher Keller, Robert Davidson, Jerry Meng, Robert Haws, Siddhartha Kattamanchi, Javad Mojarrab, Unnikrishnan Pillai, Richard Lafayette, Michelle O'Shaughnessy, Fahameedah Kamal, Kshama Mehta, Bruce Baker, Mario Ruiz, Praveena Jyothinagaram, Usha Peri, William Paxton, James Tumlin, Kerri McGreal, Ellen McCarthy, Cassandra Kimber, Archana Gautam, Kassem Khalil, Viet Nguyen, Raffi Minasian, Dariush Arfaania, Sam Daneshvari, Michel Zakari, Artashes Patrikyan, Rouzbeh Afsari, Christine Ayvazyan, Faisal Fakih, Mark Lagatta, Alfred Rodriguez, Jorge Enrique Monroy Avella, Ramachandra Patak, Jigar Kadakia, Gerald Appel, Wooin Ahn, Bradley Nelson, Allyson Medina, Syeda Ahmad, Yonatan Peleg, Nisha Clement, Ian Chiu, Elizabeth Hendren, Andrew Bomback, Pietro Canetta, Bruce Spinowitz, Chaim Charytan, Nishita Parikh, Sheng Kuo, Ritesh Raichoudhury, Mirela Dobre, Lavinia Negrea, Aparna Padiyar, Arksarapuk Jittirat, Nishigandha Pradhan, Ranjit Dhelaria, Saravanan Balamuthusamy, Machaiah Madhrira, Thomas Powell, Howard Lifland, Asha Bailey, Sarah Ashley Ford Sightler, Meera Patel Suthar, Heather Green, Samir Parikh, Isabelle Ayoub, Salem Almaani, Gabriel Contreras, Alessia Fornoni, Yelena Drexler, Abdallah Geara, Brittany Sheridan, Gaia Coppock, Jonathan Hogan, Carlos Gonzalez, Shamik Bhadra, Pradip Chowdhury, Kay Kyaw, May Tan, Lathika Raakesh, Elder Mendoza, Veronica Viramontes, Asghar Chaudhry, Juan Carbonell, Rajdeep Gadh, Victor Fernandez, Mohamad Kassem, Radu Jacob, Karen Wilder, Britt Newsome, Kathryn Klamm, Irina Suyumova, Laura Ann Kooienga, Catherine Janko, Dana Rizk, Bruce Julian, Dawn Caster, Erika Perez, Gunjan Garg, Nayan Gowda, Suneel Udani, Sreedhar Mandayam, Biruh Workeneh, Ali Assefi, Barbara Greco, Michael Germain, Jusmin Patel, Sarah Quinn, James Sullivan, Jeffrey Glaze, Phillip Madonia, Kellyn McMahon, Harold Giles, Sharon Adler, and Tiane Dai

Subjects
General Medicine
Published
2023

22. A Quality Improvement Project to Minimize COVID-19 Infections in Patients Receiving Haemodialysis and the Role of Routine Surveillance Using Nose and Throat Swabs for SARS-CoV-2 rRT-PCR and Serum Antibody Testing

Author

Dimitrios Poulikakos, Rajkumar Chinnadurai, Yvonne Mcgee, Simon Gray, Toni Clough, Nicola Clarke, Tracey Murphy, Olivia Wickens, Carol Mitchell, Denise Darby, Joel Paul, Paul Chadwick, Su Sethi, Smeeta Sinha, Philip A. Kalra, and Rosie Donne

Subjects
Haemodialysis, Clinical Practice: Research Article, Infection prevention control measures, Renal Dialysis, Reverse Transcriptase Polymerase Chain Reaction, SARS-CoV-2, Humans, Pharynx, COVID-19, Antibodies, Viral, Quality Improvement, Antibodies
Abstract

Background: Patients receiving in-centre haemodialysis (ICHD) are highly vulnerable to COVID-19. Objective: We created a quality improvement (QI) project aimed to eliminate outbreaks of COVID-19 in haemodialysis units and evaluated the utility of surveillance rRT-PCR test and SARS-CoV-2 serum antibodies for prompt identification of patients infected with COVID-19. Methods: A multifaceted QI programme including a bundle of infection prevention control (IPC) measures was implemented across 5 ICHD units following the first wave of the pandemic in June 2020. Primary outcomes evaluated before and after QI implementation were incidence of outbreaks and severe COVID-19 illness defined as COVID-19-related death or hospitalization. Secondary outcomes included the proportion of patients identified in the pre-symptomatic/asymptomatic phase on surveillance rRT-PCR screening and the incidence and longevity of SARS-CoV-2 antibody response. Results: Following the implementation of the QI project, there were no further outbreaks. Pre- and post-implementation comparison showed a significant reduction in COVID-19-related mortality and hospitalization (26 vs. 13 events, respectively, p < 0.001). Surveillance rRT-PCR screening identified 39 asymptomatic or pre-symptomatic cases out of a total of 59 rRT-PCR-positive patients (39/59, 66%). SARS-CoV-2 antibody levels were detected in 72/74 (97%) rRT-PCR-positive patients. Amongst rRT-PCR-positive patients diagnosed before August 2020, 96% had detectable antibodies until January 2021 (days from the rRT-PCR test to last antibody testing, 245–280). Conclusions: Systematic implementation of a bundle of IPC measures using QI methodology and surveillance rRT-PCR eliminated outbreaks in HD facilities. Most HD patients mount and sustain antibody response to COVID-19 for over 8 months.

Published
2021

23. Native and transplant kidney histopathological manifestations in association with COVID-19 infection: A systematic review

Author

Henry H.L. Wu, Vishnu Jeyalan, Philip A. Kalra, Arvind Ponnusamy, Rajkumar Chinnadurai, Smeeta Sinha, and Joshua Storrar

Subjects
Transplantation, medicine.medical_specialty, Systematic Reviews, Coronavirus disease 2019 (COVID-19), SARS-CoV-2, urogenital system, business.industry, Kidney biopsy, COVID-19, Histopathology, Transplant kidney, Transplant, surgical procedures, operative, Internal medicine, Medicine, business
Abstract

BACKGROUND Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in clinically significant multi-system disease including involvement in the kidney. The underlying histopathological processes were unknown at the start of the pandemic. As case reports and series have been published describing the underlying renal histopathology from kidney biopsies, we have started to gain an insight into the renal manifestations of this novel disease. AIM To provide an overview of the current literature on the renal histopathological features and mechanistic insights described in association with coronavirus disease 2019 (COVID-19) infection. METHODS A systematic review was performed by conducting a literature search in the following websites-‘PubMed’, ‘Web of Science’, ‘Embase’ and ‘Medline-ProQuest’ with the following search terms-“COVID-19 AND kidney biopsy”, “COVID-19 AND renal biopsy”, “SARS-CoV-2 AND kidney biopsy” and “SARS-CoV-2 AND renal biopsy”. We have included published data up until February 15, 2021, which includes kidney biopsies (native, transplant and postmortem) from patients with COVID-19. Data on clinical presentation, histopathological features, management and outcome was extracted from the reported studies. RESULTS The total number of biopsies reported on here is 288, of which 189 are postmortem, 84 native and 15 transplants. The results are varied and show underlying pathologies ranging from collapsing glomerulopathy and acute tubular injury (ATI) to anti-nuclear cytoplasmic antibody associated vasculitis and pigment nephropathy. There was variation in the specific treatment used for the various renal conditions, which included steroids, hydroxychloroquine, eculizumab, convalescent plasma, rituximab, anakinra, cyclophosphamide and renal replacement therapy, amongst others. The pathological process which occurs in the kidney following COVID-19 infection and leads to the described biopsy findings has been hypothesized in some conditions but not others (for example, sepsis related hypoperfusion for ATI). It is important to note that this represents a very small minority of the total number of cases of COVID-19 related kidney disease, and as such there may be inherent selection bias in the results described. Further work will be required to determine the pathogenetic link, if any, between COVID-19 and the other renal pathologies. CONCLUSION This report has clinical relevance as certain renal pathologies have specific management, with the implication that kidney biopsy in the setting of renal disease and COVID-19 should be an early consideration, dependent upon the clinical presentation.

Published
2021

24. Peptide <scp>GAM</scp> immunoadsorption in <scp> anti‐PLA 2 R </scp> positive autoimmune membranous nephropathy. The <scp>PRISM</scp> trial

Author

Patrick Hamilton, Prasanna Hanumapura, James Ritchie, Kieran Blaikie, Smeeta Sinha, Sandip Mitra, Paul Brenchley, and Durga Kanigicherla

Subjects
Autoimmune disease, medicine.medical_specialty, Proteinuria, business.industry, Autoantibody, Renal function, Hematology, General Medicine, medicine.disease, Gastroenterology, Tolerability, Membranous nephropathy, Internal medicine, medicine, medicine.symptom, Immunoadsorption, business, Nephrotic syndrome
Abstract

Membranous nephropathy associated with anti-PLA2 R autoantibody is a significant cause of nephrotic syndrome worldwide. Treatment remains empiric with a significant side-effect burden despite an increase in our understanding of the disease. We studied the effect of selectively removing this pathogenic autoantibody using immunoadsorption in adult patients with biopsy proven anti-PLA2 R membranous nephropathy. This was a multicenter, single-arm prospective clinical trial carried out in the United Kingdom. Twelve patients underwent five consecutive sessions of peptide GAM immunoadsorption with 12 months follow-up. Primary outcome was anti-PLA2 R titer at week 2. Secondary outcomes were safety and tolerability of therapy, antibody profile, and change in proteinuria, renal excretory function, serum albumin, total immunoglobulin, and quality of life at weeks 12, 24, and 52. Patients were also stratified by the presence or absence of the high-risk allele (heterozygous or homozygous for HLA-DQA1*05). Median pretreatment anti-PLA2 R was 702.50 U/mL, 1045.00 U/mL at week 2 (P-value .023) and 165.00 U/mL at week 52 (P-value .017). The treatment was well tolerated and safe. Two patients required rescue immunosuppression during the follow-up period. There was a significant improvement in serum albumin with a median at baseline of 20.50 g/L rising to 25.00 g/L at week 52 (P-value

Published
2021

25. The Role of Iron in Calciphylaxis-A Current Review

Author

Olivia Wickens, Sharmilee Rengarajan, Rajkumar Chinnadurai, Ian Ford, Iain C. Macdougall, Philip A. Kalra, and Smeeta Sinha

Subjects
General Medicine
Abstract

Calcific uraemic arteriolopathy (CUA), also known as calciphylaxis, is a rare and often fatal condition, frequently diagnosed in end-stage renal disease (ESRD) patients. Although exact pathogenesis remains unclear, iron supplementation is suggested as a potential risk factor. Iron and erythropoietin are the main stay of treatment for anaemia in ESRD patients. Few observational studies support the role of iron in the pathogenesis of calciphylaxis although data from the pivotal trial was not strongly supportive of this argument, i.e., no difference in incidence of calciphylaxis between the low-dose and high-dose iron treatment arms. Elevated levels of vascular cell adhesion molecules in association with iron excess were postulated to the pathogenesis of CUA by causing inflammation and calcification within the microvasculature. In-addition, oxidative stress generated because of iron deposition in cases of systemic inflammation, such as those seen in ESRD, may play a role in vascular calcification. Despite these arguments, a direct correlation between cumulative iron exposure with CUA incidence is not clearly demonstrated in the literature. Consequently, we do not have evidence to recommend iron reduction or cessation in ESRD patients that develop CUA.

Published
2022

26. The CALCIPHYX study: a randomized, double-blind, placebo-controlled, Phase 3 clinical trial of SNF472 for the treatment of calciphylaxis

Author

Dinesh Chatoth, Lisa J. Gould, Kevin J Carroll, Thomas E Serena, Claire Padgett, Sharon M. Moe, Sagar U. Nigwekar, Joan Perelló, Smeeta Sinha, Alex Gold, Jeffrey Hymes, George Aronoff, Vincent Brandenburg, Glenn M. Chertow, and Stephan Miller

Subjects
rationale, Transplantation, medicine.medical_specialty, Calciphylaxis, controlled clinical trial, calciphylaxis, business.industry, design, SNF472, Phases of clinical research, medicine.disease, Placebo, Double blind, Nephrology, Internal medicine, medicine, Original Article, AcademicSubjects/MED00340, business
Abstract

Background Calcific uraemic arteriolopathy (CUA; calciphylaxis) is a rare disease seen predominantly in patients receiving dialysis. Calciphylaxis is characterized by poorly healing or non-healing wounds, and is associated with mortality, substantial morbidity related to infection and typically severe pain. In an open-label Phase 2 clinical trial, SNF472, a selective inhibitor of vascular calcification, was well-tolerated and associated with improvement in wound healing, reduction of wound-related pain and improvement in wound-related quality of life (QoL). Those results informed the design of the CALCIPHYX trial, an ongoing, randomized, placebo-controlled, Phase 3 trial of SNF472 for treatment of calciphylaxis. Methods In CALCIPHYX, 66 patients receiving haemodialysis who have an ulcerated calciphylaxis lesion will be randomized 1:1 to double-blind SNF472 (7 mg/kg intravenously) or placebo three times weekly for 12 weeks (Part 1), then receive open-label SNF472 for 12 weeks (Part 2). All patients will receive stable background care, which may include pain medications and sodium thiosulphate, in accordance with the clinical practices of each site. A statistically significant difference between the SNF472 and placebo groups for improvement of either primary endpoint at Week 12 will demonstrate efficacy of SNF472: change in Bates-Jensen Wound Assessment Tool-CUA (a quantitative wound assessment tool for evaluating calciphylaxis lesions) or change in pain visual analogue scale score. Additional endpoints will address wound-related QoL, qualitative changes in wounds, wound size, analgesic use and safety. Conclusions This randomized, placebo-controlled Phase 3 clinical trial will examine the efficacy and safety of SNF472 in patients who have ulcerated calciphylaxis lesions. Patient recruitment is ongoing.

Published
2021

27. Obesity and Chronic Kidney Disease: A Current Review

Author

Saira Nawaz, Rajkumar Chinnadurai, Saif Al‐Chalabi, Philip Evans, Philip A. Kalra, Akheel A. Syed, and Smeeta Sinha

Subjects
obesity, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, dialysis, chronic kidney disease, transplantation
Abstract

Background: Obesity poses significant challenges to healthcare globally, particularly through its bi-directional relationship with co-morbid metabolic conditions such as type 2 diabetes and hypertension. There is also emerging evidence of an association between obesity and chronic kidney disease (CKD) which is less well characterized. Methods: A literature search of electronic libraries was conducted to identify and present a narrative review of the interplay between obesity and CKD. Findings: Obesity may predispose to CKD directly as it is linked to the histopathological finding of obesity-related glomerulopathy and indirectly through its widely recognized complications such as atherosclerosis, hypertension, and type 2 diabetes. The biochemical and endocrine products of adipose tissue contribute to pathophysiological processes such as inflammation, oxidative stress, endothelial dysfunction, and proteinuria. The prevention and management of obesity may prove critical in counteracting both the development and advancement of CKD. Moreover, measures of abdominal adiposity such as waist circumference, are generally associated with worse morbidity and mortality in individuals receiving maintenance hemodialysis. Conclusion: Obesity is a risk factor for the onset and progression of CKD and should be recognized as a potential target for a preventative public health approach to reduce CKD rates within the general population. Future research should focus on the use of glucagon-like peptide-1 receptor agonists and sodium–glucose cotransporter 2 inhibitors in patients with CKD and obesity due to their multi-faceted actions on major outcomes.

Published
2022

28. Calciphylaxis in end-stage kidney disease: outcome data from the United Kingdom Calciphylaxis Study

Author

Janet Hegarty, Philip A. Kalra, Abby Huckle, Rajkumar Chinnadurai, and Smeeta Sinha

Subjects
Male, Nephrology, medicine.medical_specialty, Renal Dialysis, Internal medicine, medicine, Humans, Mortality, Renal Insufficiency, Chronic, Risk factor, Calciphylaxis, business.industry, Mortality rate, End-stage kidney disease, Middle Aged, medicine.disease, United Kingdom, Natural history, Haemodialysis, Propensity score matching, Cohort, Kidney Failure, Chronic, Original Article, Female, business, Kidney disease
Abstract

Background and aims Calciphylaxis is a rare condition associated with very high mortality in patients with end-stage kidney disease. Data from country-based registries have been an invaluable resource for a better understanding of the natural history and management for this condition. This study aimed to investigate the current management strategies and outcomes of patients enrolled in the United Kingdom Calciphylaxis study (UKCS). Methods The study was conducted on 89 patients registered in the UKCS since 2012. The initial analysis included a description of the baseline characteristics, management strategies and outcomes on follow-up until May 2020. Further analysis included a comparison of the mortality outcome of the UKCS patients who were receiving haemodialysis with a propensity score matched cohort of haemodialysis patients from the Chronic Renal Insufficiency Standards Implementation Study- Haemodialysis (CRISIS-HD). Results Median age of the cohort was 59 years, with a predominance of females (61%) and Caucasian (95%) ethnicity. About 54% of the patients were diabetic and 70% were receiving haemodialysis at study entry. The skin lesions were mostly distributed in the lower extremities (48%). Sodium thiosulphate and calcimimetic were the most widely used management strategies. The mortality rate was 72 deaths per hundred patient-years (50 deaths observed in 69.5 patient years). Complete wound healing was noted in 17% and bacteraemia was reported in 26% of patients. In a comparative analysis of the matched haemodialysis patients, the presence of calciphylaxis in 62 patients showed a strong association with all-cause mortality (HR 6.96; p Conclusions This UK wide study strengthens the evidence that calciphylaxis is a strong and independent risk factor associated with all-cause mortality; no significant benefit was shown with any individual treatment modality. Until further evidence becomes available, a multifaceted approach would be the appropriate treatment strategy in the management of this extremely serious condition. Graphic abstract

Published
2021

29. MO478: The Epidemiology of Anca-Associated Vasculitis at a Single Centre Over Two Decades

Author

Josh Storrar, Helen Alderson, Nina Brown, Edmond O'riordan, Smeeta Sinha, and Philip A Kalra

Subjects
Transplantation, Nephrology
Abstract

BACKGROUND AND AIMS ANCA-associated vasculitis (AAV) refers to a group of conditions in which the end result is systemic injury of small blood vessels, resulting in damage to distinct organ systems including the lung, kidneys, ear, nose and throat. A characteristic, although not exclusive feature, is the development of anti-neutrophil cytoplasmic antibodies (ANCA) against specific proteins within the neutrophil-leucocyte proteinase 3 (PR3) and myeloperoxidase (MPO). The incidence varies according to geographic location but is ∼20 cases/million/year. The age of onset is usually between 45–75 years old, with a male: female ratio of 1:1. Without treatment, it is life-threatening; the aim of treatment is to induce remission with a strong immunosuppressive induction regimen followed by a maintenance phase. The risk of relapse remains. Here, we assessed the epidemiology of AAV >2 decades at our centre (Salford Royal Hospital, UK) with particular reference to severity of disease at presentation, ANCA positivity and outcomes. METHOD Patients with a diagnosis of AAV (either granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) or eosinophilic granulomatosis with polyangiitis (EGPA)) were identified from our database between January 2000 and December 2021 (see Figure 1). Diagnosis was based on clinical features, ANCA result and kidney biopsy findings. A total of 47 were excluded and demographic data, co-morbidities, laboratory values (including baseline creatinine, eGFR, proteinuria, ANCA positivity), treatment given and outcomes were collected in the remaining sample. Analysis determined (i) basic demographic description of our cohort, (ii) median baseline creatinine, eGFR and proteinuria, (iii) those with an initial requirement for renal replacement therapy (RRT) at presentation, (iv) ANCA positivity rates and (v) outcomes including progression to RRT and mortality. RESULTS The evaluable cohort totalled 369 patients (see Table 1). Of these, 194 were male (52.6%), and the median age at presentation was 73 (IQR 60–82) years; 91.9% were Caucasian. Median baseline creatinine was 165 µmol/L (93–338), eGFR 33 mL/min/1.73 m2 (15–66) and proteinuria 98 g/mol (25–258). ANCA was measured in 363 (98.4%), of which c-ANCA and or PR3 positivity was seen in 142 (39.1%), and p-ANCA and or MPO positivity was seen in 148 (40.8%). In a small number, atypical ANCA was seen (1.9%) or ANCA was obscured by anti-nuclear factor (ANF) (2.8%). An immediate requirement for RRT at presentation was seen in 26 (7%). Progression to RRT at any time point over the follow up period was observed in 86 (23.3%), with the first RRT modality being haemodialysis in 64 (17.3%), peritoneal dialysis in 20 (5.4%) and transplant in 2 (0.5%). A total of 147 patients (39.8%) died over the follow-up period. A combined outcome of progression to RRT or death was seen in 191 (51.8%). CONCLUSION We show that patients present with AAV at an advanced age and with significant renal involvement (median baseline eGFR of 33 mL/min/1.73 m2 in our study). The distribution of PR3 and MPO positive vasculitis is similar, although there were a significant number of ANCA negative patients in our cohort. There were differences in concordance between c-ANCA and PR3 positivity, along with p-ANCA and MPO positivity, which may be explained by historical differences in testing. There remains a significant risk of progression to the requirement for RRT or death: 51.8% observed over our follow-up period of two decades.

Published
2022

30. MO240: The Evolution and Epidemiology of Membranous Nephropathy at a Single Centre Over Two Decades

Author

Josh Storrar, Tarra Gill-Taylor, Rajkumar Chinnadurai, Smeeta Sinha, and Philip A Kalra

Subjects
Transplantation, Nephrology
Abstract

BACKGROUND AND AIMS Membranous nephropathy (MN) commonly presents with nephrotic syndrome and carries significant risk of progression to end-stage kidney disease (ESKD) (33% without treatment, 10%–20% with). Patients may spontaneously remit (up to 40%), but are also at risk of relapse. A total of 80% of cases are primary (kidney-specific) and the majority of these are associated with antibodies to the M-type phospholipase A2 receptor (anti-PLA2R) or thrombospondin type 1 domain containing 7A antibodies (THS7DA). Treatment ranges from supportive care with renin–angiotensin system (RAS) blockade through to immunosuppression. Here we assessed the epidemiology of MN over 20 years at our centre (Salford Royal Hospital, UK) with particular reference to treatment administered and key clinical outcomes. METHOD A total of 238 patients with kidney biopsy-proven MN were identified from the local database between January 2000 and December 2020. Twenty-one were excluded (see Fig. 1) resulting in a total of 217 patients in whom demographic data, co-morbidities, remission and relapse rates, baseline laboratory values, treatment given, and outcomes were collected. Analyses compared effects of (i) immunosuppressed versus non-immunosuppressed, (ii) effect of modified Ponticelli versus other forms of immunosuppression and (iii) rates of remission. Univariate and multivariate cox regression determined factors that were associated with increased risk of renal replacement therapy (RRT) or death. RESULTS A total of 63.6% of the cohort were male, 88% Caucasian, 10.1% diabetic, 50.2% hypertensive and 15.2% had coexisting cardiovascular disease (Table 1). A total of 82.0% had primary MN. Median baseline eGFR was 72.7 mL/min/1.73 m2 and median baseline uPCR was 664 g/mol. A total of 157 patients (72.4%) went into remission (either spontaneous—75 (47.8%) or with treatment—85 (52.2%)), and of these 41.4% subsequently relapsed. A total of 89.4% received RAS blockade and 48.8% received immunosuppression. The median follow-up period was 56 months; 9.7% progressed to ESKD and 32.3% died. Patients who received immunosuppression had significantly more proteinuria than those who did not (765 g/mol versus 514 g/mol, P ≤ 0.001), were more likely to relapse (53.7% versus 28.0%, p ≤0.001) and were more likely to require RRT (15.1% versus 4.9%, P = .028). Those who received modified Ponticelli were less likely to relapse than those who received other forms of immunosuppression (34% versus 46%, P = .019), less likely to require RRT (3% versus 22%, P = .018) and less likely to die (11% versus 38%). Multivariate cox regression showed that pre-existing cardiovascular disease was a risk factor for death (HR 2.47, P < .001) and higher baseline eGFR and use of RAS blockade was associated with reduced risk of death (HR 0.98, P < .001 and HR 0.34, P = .012, respectively). CONCLUSION Despite advances in knowledge of underlying pathogenesis and increased treatment options, MN continues to pose a significant risk of progression to ESKD and death. This real-world study suggests that immunosuppression with modified Ponticelli is associated with lower rates of progressive CKD compared with MMF and calcineurin-inhibitor based therapy. Whilst many patients respond to treatment and can achieve remission, a significant proportion of these subsequently relapse. Identifying these patients early with judicial use of appropriate immunosuppression is key.

Published
2022

31. Defining the Role of SGLT2 Inhibitors in Primary Care: Time to Think Differently

Author

Marc Evans, Angharad R. Morgan, Stephen C. Bain, Sarah Davies, Umesh Dashora, Smeeta Sinha, Samuel Seidu, Dipesh C. Patel, Hannah Beba, and W. David Strain

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine
Abstract

Disease burden in people with diabetes is mainly driven by long-term complications such as cardiovascular disease, heart failure and chronic kidney disease. This is a consequence of the interconnection between the cardiovascular, renal and metabolic systems, through a continuous chain of events referred to as 'the cardiorenal metabolic continuum'. Increasing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT2is) have beneficial effects across all stages of the cardiorenal metabolic continuum, reducing morbidity and mortality in a wide range of individuals, from those with diabetes and multiple risk factors to those with established heart failure and chronic kidney disease, regardless of the presence of diabetes. Despite this robust evidence base, the complexity of label indications and misconceptions concerning potential side effects have resulted in a lack of clear understanding in primary care regarding the implementation of SGLT2is in clinical practice. With this in mind, we provide an overview of the clinical and economic benefits of SGLT2is across the cardiorenal metabolic continuum together with practical considerations in order to help address some of these concerns and clearly define the role of SGLT2is in primary care as a holistic outcomes-driven treatment with the potential to reduce disease burden across the cardiorenal metabolic spectrum.

Published
2022

33. Peptide GAM immunoadsorption in anti-PLA

Author

Patrick, Hamilton, Durga, Kanigicherla, Prasanna, Hanumapura, Kieran, Blaikie, James, Ritchie, Smeeta, Sinha, Paul, Brenchley, and Sandip, Mitra

Subjects
Adult, Aged, 80 and over, Male, Receptors, Phospholipase A2, Plasmapheresis, Middle Aged, Glomerulonephritis, Membranous, Autoimmune Diseases, Humans, Female, Prospective Studies, Peptides, Aged, Autoantibodies
Abstract

Membranous nephropathy associated with anti-PLA

Published
2021

34. Point-of-Care Creatinine to Assist Clinical Decision Making in Suspected Sepsis in the Community

Author

Leonard Ebah, Susan Simpson, Peter Elton, Dimitrios Poulikakos, Khalid Alshawy, Joshua Storrar, Denise Darby, Smeeta Sinha, and James Ritchie

Subjects
Sepsis, Creatinine, chemistry.chemical_compound, medicine.medical_specialty, chemistry, Clinical decision making, business.industry, medicine, medicine.disease, business, Intensive care medicine, General Nursing, Point of care
Published
2019

35. SNF472: mechanism of action and results from clinical trials

Author

Paolo Raggi, Smeeta Sinha, and Glenn M. Chertow

Subjects
Oncology, medicine.medical_specialty, Phytic Acid, medicine.medical_treatment, 030232 urology & nephrology, Phases of clinical research, Inflammation, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Dystrophic calcification, Renal Dialysis, Internal medicine, Internal Medicine, Medicine, Humans, Vascular Calcification, business.industry, medicine.disease, Clinical trial, medicine.anatomical_structure, Nephrology, Kidney Failure, Chronic, Hemodialysis, Aortic valve calcification, medicine.symptom, business, Kidney disease, Artery
Abstract

Purpose of review Vascular calcification (VC) is associated with increased cardiovascular event rates, particularly in patients with end-stage kidney disease (ESKD). Dysregulated mineral metabolism and inflammation have been shown to promote VC, however, treatment options targeting VC specifically are not available. This review outlines the pathophysiological mechanisms contributing to VC in ESKD and describes recent studies evaluating the effects of the first-in-class inhibitor of VC, SNF472. Recent findings SNF472 directly inhibits calcium phosphate crystal formation and aggregation. SNF472 has completed early phase clinical trials with a favourable safety profile and Phase 2 clinical trial data have shown attenuation of coronary artery and aortic valve calcification in patients receiving hemodialysis. Summary Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD.

Published
2021

36. MO306IGA NEPHROPATHY: A 20 YEAR RETROSPECTIVE SINGLE CENTRE EXPERIENCE

Author

Rajkumar Chinnadurai, Josh Storrar, Fahmida Mannan, Reuben Roy, Philip A. Kalra, and Smeeta Sinha

Subjects
Transplantation, medicine.medical_specialty, medicine.diagnostic_test, business.industry, medicine.medical_treatment, Glomerulonephritis, medicine.disease, Nephropathy, Therapeutic immunosuppression, Single centre, Nephrology, Internal medicine, Biopsy, Epidemiology, medicine, Hemodialysis, business
Abstract

Background and Aims IgA nephropathy is the most common glomerulonephritis worldwide. The clinical course is heterogeneous and not always easy to predict. As such, determining which patients to treat with immunosuppression has been the cause of much debate. Over recent years there has been a focus on risk prediction to help with treatment decisions (such as the widely validated International IgA Risk Prediction Tool). Here, we present a 20 year retrospective study from a single centre with the following aims: to describe the epidemiology of our cohort, to assess outcomes (such as progression to ESKD requiring RRT, mortality), and to determine if treatment choices have changed over time. Method We collected all cases of IgA nephropathy from our biopsy database between January 2020 and December 2019. This totalled 525 biopsies. Of these, a number were excluded from analysis, including transplant biopsies and repeat biopsies in the same patient. After exclusion, the original 525 biopsies were narrowed down to 452 patients for analysis. We collected demographic data for each patient, along with creatinine and proteinuria values over time, MEST-C scores, progression to ESKD, mortality, use of RAAS blockade and immunosuppressants. Initial analysis was performed using Excel. We plan to perform further multivariate Cox regression analysis to determine if there are associations with progression to ESKD such as degree of proteinuria, MEST-C scores and immunosuppression treatment. Results We identified 452 patients with biopsy confirmed IgA nephropathy at our centre between January 2000 and December 2019. 138 (30.5%) were female and 314 (69.4%) were male. The average age at time of biopsy was 45.7 years. Mortality over this period was 19.2% (87 patients). 126 (27.9%) progressed to ESKD requiring RRT, 6 (1.3%) required temporary dialysis whilst 313 (69.2%) did not require RRT. With regards to treatment, 329 (72.8%) were treated with RAAS blockade in comparison to 85 (18.8%) who were not (in 38 patients this was unclear). No immunosuppression was used in 349 (77.2%), whilst a combination of prednisolone; IV cyclophosphamide and prednisolone; and MMF and prednisolone was used in 97 (21.5%). Conclusion We present here a large single centre dataset of IgA nephropathy patients over a 20 year period. We show that there remains a significant risk of progression to ESKD over time. It is important to identify those patients most at risk of progression early on in their disease course so that optimal treatment can be initiated. Further analysis of this dataset will allow us to assess whether treatment strategies in recent years has had a beneficial effect on outcomes, and also to assess the correlation between MEST-C scores and treatment decisions.

Published
2021

37. Development of the BWAT-CUA Scale to Assess Wounds in Patients with Calciphylaxis

Author

Thomas E. Serena, Smeeta Sinha, and Lisa J. Gould

Subjects
medicine.medical_specialty, Medicine (General), wound, Clinical Biochemistry, 030232 urology & nephrology, Phases of clinical research, rating, scale, 03 medical and health sciences, Study Protocol, 0302 clinical medicine, R5-920, medicine, Clinical endpoint, In patient, 030212 general & internal medicine, Prospective cohort study, Vascular calcification, Calciphylaxis, business.industry, calciphylaxis, medicine.disease, healing, Surgery, Clinical research, business, Kidney disease
Abstract

Calcific uremic arteriolopathy (CUA; calciphylaxis) is a severe form of vascular calcification with no approved therapies. A standardized wound assessment tool is needed to evaluate changes in calciphylaxis wounds over time. A prospective, single-arm study of 14 patients with calciphylaxis reported improvement for the primary endpoint of wound healing using the 13-item Bates-Jensen Wound Assessment Tool (BWAT), although that tool was developed for assessment of pressure ulcers. This report describes development of BWAT-CUA, an 8-item modification of BWAT focusing on prototypical features of calciphylaxis lesions. The BWAT-CUA has a range of 8 (best) to 40 (worst) and was used ad hoc to analyze BWAT data collected in the prospective study. Using BWAT-CUA, relative improvement in calciphylaxis wounds was 30% overall (from 21.2 to 14.9; p = 0.0016) and 34% in the subset of 12 patients with ulceration at baseline (from 23.3 to 15.3; p = 0.0002). BWAT-CUA is a primary endpoint in an ongoing randomized, placebo-controlled phase 3 study of SNF472 recruiting patients with end-stage kidney disease and at least one ulcerated calciphylaxis lesion. BWAT-CUA, a newly developed tool for assessment of calciphylaxis wound severity and improvements over time, may be used in clinical research and in clinical practice.

Published
2021

38. Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study

Author

David A, Bushinsky, Paolo, Raggi, Jordi, Bover, Markus, Ketteler, Antonio, Bellasi, Mariano, Rodriguez, Smeeta, Sinha, Rekha, Garg, Joan, Perelló, Alex, Gold, Glenn M, Chertow, and Tarun, Bansal

Subjects
Adult, Male, medicine.medical_specialty, Phytic Acid, Epidemiology, medicine.medical_treatment, Population, 030232 urology & nephrology, Urology, 030204 cardiovascular system & hematology, Critical Care and Intensive Care Medicine, Placebo, 03 medical and health sciences, 0302 clinical medicine, Cardiovascular calcification, Double-Blind Method, Bone Density, Renal Dialysis, medicine, Humans, education, Aged, Bone mineral, Aged, 80 and over, Transplantation, education.field_of_study, business.industry, Original Articles, Middle Aged, Confidence interval, Nephrology, Female, Hemodialysis, Aortic valve calcification, Agatston score, business
Abstract

Background and objectives In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO. Design, setting, participants, & measurements Patients with coronary artery calcification at screening (Agatston score of 100–3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance. Results Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were −1.5% (−2.7% to −0.3%), −1.5% (−2.7% to −0.4%), and −2.5% (−3.8% to −1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were −0.3% (−1.6% to 1.0%), −1.0% (−2.3% to 0.2%), and −2.6% (−4.0% to −1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Conclusions Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups. Clinical Trial registry name and registration number: Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028

Published
2020

39. Pain management in patients with end-stage renal disease and calciphylaxis- a survey of clinical practices among physicians

Author

Mary Miller, Smeeta Sinha, Aoife Lowney, and Rajkumar Chinnadurai

Subjects
Advance care planning, Nephrology, medicine.medical_specialty, Palliative care, Referral, Amitriptyline, Pregabalin, 030232 urology & nephrology, Pain, Disease, Pain, Procedural, Guidelines, lcsh:RC870-923, End stage renal disease, Advance Care Planning, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Internal medicine, medicine, Humans, Practice Patterns, Physicians', Palliative Medicine, Survey, Intensive care medicine, Referral and Consultation, Acetaminophen, Analgesics, Calciphylaxis, business.industry, Breakthrough Pain, Guideline, Analgesics, Non-Narcotic, lcsh:Diseases of the genitourinary system. Urology, medicine.disease, United Kingdom, Pain management, Analgesics, Opioid, Opioids, Kidney Failure, Chronic, Gabapentin, business, Research Article
Abstract

Background Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline. Methods An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options. Results One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time. Conclusion There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.

Published
2020

40. Pain management in patients with end-stage renal disease and calciphylaxis- A survey among physicians and clinical practice recommendations

Author

Mary Miller, Smeeta Sinha, Aoife Lowney, and Rajkumar Chinnadurai

Subjects
Clinical Practice, Calciphylaxis, medicine.medical_specialty, business.industry, Medicine, In patient, Pain management, business, medicine.disease, Intensive care medicine, End stage renal disease
Abstract

Background Calciphylaxis is a rare condition usually seen in patients with end-stage renal disease. Pain is a hallmark of this condition and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is challenging with variable approaches across the United Kingdom (UK) and internationally. A knowledge and practice survey was conducted to establish current practice in the management of pain in patients with calciphylaxis, in the UK. Based on the results and clinical experience the authors suggest a clinical practice guideline.Methods An online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. The questionnaire included a mix of open-ended questions and questions with drop down options. Results One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine; the remaining 46 (43%) were from renal medicine. 31 (30%) respondents across both specialties had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). A referral to the palliative care team was undertaken by 18% of renal physicians, 32% referred to the pain team and 50% referred to both. Only 3% of the palliative medicine respondents indicated that they had received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain. Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. The importance of advance care planning was highlighted with 72% undertaking advanced care planning discussions often or most of the time.Conclusion There was wide variation in the current practice of pain management in patients with calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to specialists in pain management is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated has facilitated the development of a clinical practice guideline to support complex pain management in a group of patients with multiple comorbidities.

Published
2020

41. SARS-CoV-2 antibody screening in healthcare workers in a tertiary centre in North West England

Author

Philip A. Kalra, Dimitrios Poulikakos, and Smeeta Sinha

Subjects
2019-20 coronavirus outbreak, biology, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), medicine.disease, biology.organism_classification, Virology, Article, Pneumonia, Infectious Diseases, North west, Pandemic, Health care, medicine, business, Antibody screening, Betacoronavirus
Published
2020
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42. SO086SNF472 CONSISTENTLY SLOWS PROGRESSION OF CORONARY CALCIFICATION IN PATIENTS ON HEMODIALYSIS: SUBGROUP ANALYSIS OF THE CALIPSO STUDY

Author

Mariano Rodriguez, Paolo Raggi, Claire Padgett, Glenn M. Chertow, Joan Perelló, David A. Bushinsky, Markus Ketteler, Jordi Bover, Antonio Bellasi, Alex Gold, Rekha Garg, and Smeeta Sinha

Subjects
Transplantation, medicine.medical_specialty, Intention-to-treat analysis, business.industry, medicine.medical_treatment, Warfarin, Subgroup analysis, medicine.disease, Nephrology, Internal medicine, Diabetes mellitus, Vitamin D and neurology, Cardiology, Medicine, Hemodialysis, business, Agatston score, Calcification, medicine.drug
Abstract

Background and Aims In the CaLIPSO study, SNF472 significantly attenuated progression of coronary artery calcium (CAC) volume score compared with placebo. This pre-specified analysis examined the effect of SNF472 on CAC progression in key subgroups of patients in CaLIPSO. Method Patients with a CAC Agatston score of 100 to 3500 at baseline were randomized to SNF472 300 mg (n=92), SNF472 600 mg (n=91), or placebo (n=91), infused during hemodialysis (HD) thrice weekly for 52 weeks. Patients received standard of care therapy, including phosphate binders and calcimimetics as determined by investigator. The primary endpoint (change in log CAC volume score from baseline to week 52 in the combined dose groups vs placebo) was analyzed for patients who received SNF472 or placebo and had an evaluable CT scan post-randomization (modified ITT population). Sensitivity analysis was also performed for the per protocol population of patients that met entry criteria, received 80% of scheduled treatment, completed the study procedures, and had both a baseline and week 52 evaluable CT scan. The analysis plan pre-specified key subgroups: age, sex, diabetes, dialysis vintage, and arteriosclerotic cardiovascular disease (ASCVD), as well as baseline use of non-calcium phosphate binders, calcium-based phosphate binders, calcimimetics, activated vitamin D, warfarin, or statins. Results Demographics and disease characteristics were similar across the treatment groups. Age (mean±SD) at baseline was 63.6±8.9 years and 39% of the patients were female; 62% had diabetes and 41% had prior ASCVD. Median dialysis vintage was 42.4 months; 33% had received hemodialysis for ≥5 years. Concomitant medications at baseline were: non-calcium phosphate binders, 62%; calcium-based phosphate binders, 28%; calcimimetics, 31%; activated vitamin D, 51%; warfarin, 8%; and statins, 64%. CAC volume progression was 11% for the combined dose groups and 20% for placebo (p=0.016). Treatment differences for CAC volume score progression from baseline to week 52 were similar across the subgroups (FIGURE). All interaction p-values were non-significant, and comparisons favored SNF472 vs placebo in each subgroup for both the modified ITT and per protocol population. Conclusion SNF472 treatment for 52 weeks attenuated CAC progression compared with placebo in all subgroups of the CaLIPSO study. These results support the potential benefit of SNF472 across a broad population of patients with cardiovascular calcification. Future studies are needed to determine the effects of SNF472 on cardiovascular events in patients receiving HD.

Published
2020

43. P0909HYPOCALCAEMIA MANAGEMENT POST PARATHYROIDECTOMY IN RENAL PATIENTS - A REVIEW OF PRACTICE

Author

Rajkumar Chinnadurai, Helen Doran, Smeeta Sinha, Tina Chrysochou, and Tricia Tay

Subjects
Parathyroidectomy, Transplantation, medicine.medical_specialty, Nephrology, business.industry, General surgery, medicine.medical_treatment, medicine, business
Abstract

Background and aims Hypocalcaemia is a common post-parathyroidectomy complication in renal patients with secondary hyperparathyroidism. This is due to reduced parathormone (PTH) mediated calcium absorption in the kidneys and increased influx of calcium to bones. Our initial study in January 2015 showed preloading patients with one alfacalcidol 2 microgram once a day for 5 days preoperatively was ineffective in reducing hypocalcaemia related complications. We re-investigated the outcomes in patients following a change in practice to use one alfacalcidol 5 microgram once a day for 5 days preoperatively. Method All patients with pre-existing chronic kidney disease (CKD) who underwent parathyroidectomy by a single surgeon in our centre between March 2016 and October 2017 were included (12 patients). The outcomes (length of hospital stay and hypocalcaemia requiring IV calcium replacements) were compared with a previous study on patients operated on by the same surgeon between April 2008 and September 2014 (24 patients). Statistical analysis was conducted using Microsoft excel and SPSS version-22. Results Twelve patients were included in this study; 5 were females. Mean age at surgery was 54 (range 45-61) years. Eight patients were on long-term haemodialysis, 3 had a functioning renal transplant and 1 had CKD stage 5. Eight patients had been receiving cinacalcet for more than one month preoperatively. Mean length of stay (LoS) was 5.3 days (range 3-10), half (n=6) were discharged four days post-op. Ten had a total parathyroidectomy, of which half (n=5) were discharged after post-op day 4. Four patients were not preloaded with 5mcg as per protocol; reasons for non-adherence to the protocol included regular prescription of alfacalcidol and physician discretion to utilise a lower dose. Patients with lower pre-op corrected calcium levels (2.4-2.6 mg/dL) stayed for a mean of 6.74 days after surgery. This was a longer LoS compared to other calcium ranges. No hypercalcemia related complications were recorded. The need for post-operative intravenous calcium use decreased from 10/24 to 2/12. Despite more patients having total parathyroidectomy and being on dialysis, a smaller proportion required IV calcium in the post-operative phase, although this was not statistically significant due to the small sample size (p=0.26). Conclusion Our study highlights that the current practice of preloading one alphacalcidol 5 mcg once a day for 5 days preoperatively in renal patients undergoing parathyroidectomy appears to be a safe and effective approach. Ongoing monitoring and further studies on a larger cohort of patients is needed to strengthen these observations.

Published
2020

44. P1408PAIN MANAGEMENT IN CALCIPHYLAXIS: A KNOWLEDGE,ATTITUDE AND PRACTICE SURVEY AMONG PHYSICIANS

Author

Smeeta Sinha, Aoife Lowney, Mary Miller, and Rajkumar Chinnadurai

Subjects
Advance care planning, Nephrology, Transplantation, Calciphylaxis, medicine.medical_specialty, Closed-ended question, Palliative care, business.industry, medicine.medical_treatment, Pain management, medicine.disease, Comorbidity, Internal medicine, medicine, Nerve block, Intensive care medicine, business
Abstract

Background and Aims Calciphylaxis is a rare disease usually seen in patients with end-stage renal disease. Pain is a hallmark of this disease and can be extremely difficult to control. Anecdotal data suggests that pain management in calciphylaxis is unsatisfactory with differing practice, variable across the United Kingdom (UK) and also around the world. This knowledge, attitude and practice (KAP) survey aims to gather information on the current practice in the management of pain in patients with calciphylaxis. Method A pre-tested online questionnaire was circulated among physicians (renal and palliative care) involved in the management of pain in calciphylaxis. (https://www.gmann.co.uk/ website/calciphylaxis-pain-management-survey.cfm). The questionnaire included a mix of open-ended questions and questions with drop down options. Results One hundred and six clinicians responded to the survey of which 60 (57%) respondents were from palliative medicine and the remainder 46 (43%) were from renal medicine. There were 31 (30%) respondents, across both specialties who had not encountered any patients with a diagnosis of calciphylaxis (renal-2, palliative care-29). 18% of renal physicians refer patients to palliative care team, 32% refer to pain team and 50% refer to both. Only 3% of the palliative medicine respondents indicated that they’d received a referral from the renal team at the time of diagnosis. Opioids were the preferred initial drug of choice for the management of all types of pain although the preferred drug varied with the specialities (Fig–1). Paracetamol was universally selected as the preferred first-choice adjuvant agent for management of all types of pain. Additional procedures to aid pain management (epidural analgesia and nerve blocks) were used by 6.6% of respondents. A majority (83%) felt the presence of infection impacts on the effectiveness of pain control. The importance of advanced care planning was also highlighted with 72% undertaking advanced care planning discussions often or most of the times. Conclusion In conclusion, there was wide variation in the current practice of management of pain in calciphylaxis, with variation between renal specialists and palliative care specialists. Referral to pain specialists is not universal despite the severe nature of the pain experienced by patients with calciphylaxis. The data generated will enable to us to develop practice guidelines to support complex pain management in a group of patients with multiple comorbidities.

Published
2020

45. P0102A REVIEW OF RENAL BIOPSIES IN A LARGE UK RENAL CENTRE- A 20 YEAR EXPERIENCE

Author

Smeeta Sinha and Amy Hudson

Subjects
Nephrology, Transplantation, medicine.medical_specialty, Kidney, medicine.diagnostic_test, business.industry, General surgery, Medical record, Transplanted kidney, Tissue specimen, medicine.anatomical_structure, Internal medicine, Biopsy, medicine, Renal biopsy, business
Abstract

Background and Aims Percutaneous renal biopsy is the mainstay of renal pathological diagnosis. Not only does it secure an accurate diagnosis, but also lends itself to guiding the prognosis of a myriad of renal disorders. An important diagnostic modality for nephrologists, they have contributed greatly to the field of nephrology, both in terms of the classification of diseases and assisting in understanding their pathogenesis. Adequacy of the tissue samples of at least ten to fifteen glomeruli is generally preferred. The aim of our retrospective study was to review the renal biopsies done in one large UK renal centre, namely Salford Royal Foundation Trust, over the last twenty years. This Trust covers a catchment area that serves approximately 1.5 million people. Method A list of all renal biopsies performed at Salford Royal Foundation Trust between January 2000 to January 2020 was generated by our pathology department. Following this, each individual biopsy report was reviewed. In addition to this, certain information was collated from individual patient records; namely patient demographics, the indication for biopsy, tissue type (native or transplant), histological diagnosis and outcomes. Our centre has an excellent electronic patient record (EPR). This enabled us to analyse full clinical data retrospectively for each case. Results Between January 2000 and January 2020 a total of 3555 renal biopsies were performed at Salford Royal Foundation Trust. These biopsies were performed solely by nephrology specialists and supervised trainees, under ultrasound guidance. 177.5 biopsies were performed on average, per year, ranging between 140 – 203. 90% of biopsies were performed on native kidneys, with 10% being performed on transplanted kidneys. 10% of biopsies had normal histology morphologically when reviewed by light microscopy. There diagnoses of these included entities minimal change disease and thin basement membrane disease most commonly. IgA nephropathy was the most common glomerular pathology identified, in keeping with the wealth of published literature. There were over 525 biopsies done confirming IgAN as the primary pathology. 7% of biopsies had a crescentic glomerular pathology when examined histologically. The main causes included crescentic IgA nephropathy and anca-associated vasculitis. Conclusion Kidney biopsies have long been regarded as safe, minimally invasive procedures are of paramount importance to our diagnostic armamentarium. Our data echoes that of already published pathology series, IgAN being the most common glomerular pathology in our series. We further plan to analyse the various conditions and their outcomes in further detail.

Published
2020

46. Mortality risk by peak serum creatinine in hospital episodes complicated by acute kidney injury

Author

Benjamin D James, Philip A. Kalra, Darren Green, Emma Flanagan, Lynne Sykes, and Smeeta Sinha

Subjects
medicine.medical_specialty, Urology, 030204 cardiovascular system & hematology, urologic and male genital diseases, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, Medicine, Humans, 030212 general & internal medicine, Hospital Mortality, Stage (cooking), Creatinine, urogenital system, business.industry, Research, Acute kidney injury, General Medicine, Acute Kidney Injury, medicine.disease, female genital diseases and pregnancy complications, Hospitals, chemistry, business
Abstract

Acute kidney injury (AKI) is common in hospitalised patients and provides valuable prognostic information, although there is suggestion of negligible mortality difference between AKI stages 2 and 3.[1,2][1] AKI stage is principally determined by proportional serum creatinine (SCr) changes, not by

Published
2020

49. First-time-in-human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification

Author

Ana Z. Canals, Miguel D. Ferrer, Pieter H. Joubert, Joan Perelló, Carolina Salcedo, and Smeeta Sinha

Subjects
Pharmacology, medicine.medical_specialty, Calciphylaxis, Calcification inhibitor, business.industry, 030232 urology & nephrology, 030204 cardiovascular system & hematology, Placebo, medicine.disease, Gastroenterology, End stage renal disease, 03 medical and health sciences, 0302 clinical medicine, Pharmacokinetics, Tolerability, Cardiovascular calcification, Pharmacodynamics, Internal medicine, Medicine, Pharmacology (medical), business
Abstract

AIMS SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS This is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation. RESULTS Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 ± 21.0%, P

Published
2018

50. Non-recruitment to and selection bias in studies using echocardiography in haemodialysis patients

Author

Aghogho Odudu, Diana Yy Chiu, John Hughes, Smeeta Sinha, Philip A. Kalra, Darren Green, and Nik Abidin

Subjects
medicine.medical_specialty, education.field_of_study, business.industry, Proportional hazards model, medicine.medical_treatment, Population, 030232 urology & nephrology, General Medicine, 030204 cardiovascular system & hematology, medicine.disease, Transplantation, 03 medical and health sciences, 0302 clinical medicine, Social deprivation, Nephrology, Internal medicine, Diabetes mellitus, medicine, Cardiology, Observational study, business, Prospective cohort study, education, Dialysis
Abstract

Background It is unknown whether patients recruited to renal cardiac imaging studies are fully representative of the investigated population and whether there are differences in characteristics and survival between participants and non-participants (excluded or declined consent). Subjects and Methods Four hundred thirty-five maintenance haemodialysis patients were screened in an observational, prospective study. Baseline demographics, laboratory results, social deprivation scores and survival data were collected from patient records. All patients were followed-up until death, renal transplantation or 16 November 2015. Results Forty-four patients were excluded (16 language barrier, 10 mental incapacity, 9 severe co-morbid illness and 9 because of immobility), 172 patients declined consent (84% due to reluctance to attend for an extra visit) and 219 patients were recruited. Excluded patients had a lower mean haemoglobin (10.2 g/dL vs 10.7 g/dL), phosphate (4.15 mg/dL vs 4.74 mg/dL), albumin (3.6 g/dL vs 3.8 g/dL) and higher C-reactive protein (3.2 mg/dL vs 1.6 mg/dL) compared with recruited patients. No difference was identified between groups for Charleston comorbidity index (P = 0.115) or social deprivation scores. After a median follow-up of 29.7 (25th–75th percentile, 21.1–34.3) months, there were 141 deaths. In a multivariable Cox regression model adjusting for BMI, age, Charleston comorbidity index, haemoglobin, albumin, smoking status and diabetes mellitus, patients who declined consent had an adjusted HR of 1.70, 95% CI 1.10–2.52, and excluded patients had an adjusted HR of 1.30, 95% CI 0.75–2.25, for all-cause mortality compared with recruited patients. Conclusions Patients recruited to the study had longer survival compared with non-participants. Research studies should document phenotypes of non-participants to aid interpretation and generalizability of results.

Published
2017

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