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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

Membranous nephropathy associated with anti-PLA

Background Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. Methods Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. Results Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). Conclusion Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.

Background and Aims Acute kidney injury (AKI) is a widely recognised serious health care issue. Up to 25% of hospital patients can develop it, with worse outcomes compared non AKI. A UK–wide audit in 2009 and our local audit in 2014 showed consistently poor AKI care including delays in detection and inconsistent management of cases. The trust set up the AKI Team in 2014 to improve AKI detection, care and outcomes. Successful implementation of a Multifaceted Quality Improvement (QI) Programme for AKI across the main hospital campus since 2015 saw significant improvement in AKI care and outcomes; recognition within 24hrs improved from 52% to 100% since 2016; there has been a 34% reduction in AKI incidence, 26% reduction in AKI length of stay (LoS) ,42% reduction in AKI days (time to recovery) and 10% less AKI associated mortality. The Trust being one of the largest acute trusts in the UK (10 hospitals across 6 sites, over 2000 beds), the QI spread represented a formidable challenge. We describe the methodology and outcomes of AKI QI spread across the trust. Method Central Campus Hospitals Improvement on this site involved setting a bespoke electronic alert coupled with education, key stake holder engagement, gradual culture change and AKI Priority Care Checklist (PCC) and use of change agent (AKI Clinical Nurse Specialist-CNS) visiting local teams and empowering them to manage AKI using Demming’s Model for Improvement A stepwise staggered similar approach was implemented first in the Women’s and Eye Hospitals followed by Children’s Hospital after a local adaptation and testing of algorithm, PCC and appointment of local change agent, a Paediatric AKI CNS. West Campus Hospital A DGH with 230 beds, 1-2 incident cases of AKI/day required a bespoke approach. The central AKI team runs an AKI alerts report and remotely alert the local multidisciplinary teams and empowering them to implement the PCC. South Campus Hospitals A large tertiary hospital merged in 2018 with an existing AKI CNS team. Detection algorithms, education material, PCC, reporting, and approach have been progressively harmonized using the Central Campus model. Data is expressed using SPC charts and analysed by t-test. Results Care process and outcome measures have seen a consistent improvement across all sites. As reported in the Central Campus, recognition of AKI within 24hrs has improved from 52% to 100% since 2016; there has been a 34% reduction in AKI incidence (p The Children’s Hospital had 24% reduction (p In the South Campus recognition of AKI has improved from 67% to 100% and 19% reduction (p In West Campus recognition is 100% but the small numbers prevent any meaningful analysis of other outcomes. Conclusion This study demonstrates how a cluster of simple interventions and approach to AKI detection and care were successfully rolled out across a multisite large complex acute care organization taking into account the local realities of each site/Hospitals whilst maintaining the core interventions.

INTRODUCTION: Membranous nephropathy (MN) is among the most common causes of nephrotic syndrome in adults worldwide. Most patients have primary MN (PMN), an autoimmune condition associated with the IgG anti-PLA2 R autoantibody. For patients with severe disease, standard of care continues to be a 6-month regime of rotating high dose steroids and immunosuppression that comes with a significant side-effect profile. Immunoadsorption is a relatively safe procedure for the extracorporeal removal of specific immunoglobulins without the need for medications.DESIGN: This is a Phase II multi-centre, single arm prospective clinical trial carried out across Northwest region of the United Kingdom to assess the safety and clinical effectiveness of immunoadsorption therapy in PMN. 12 adult patients with biopsy proven MN, nephrotic range proteinuria and serum anti-PLA2 R antibody titers of more than 170 µ/mL will undergo 5 consecutive daily sessions of immunoadsorption. Primary outcome is the reduction of serum anti-PLA2 R antibodies at day 14. Secondary outcomes are the safety and tolerability of immunoadsorption therapy in patients with primary MN at all-time points, reduction of serum anti-PLA2 R levels, proteinuria and improvement in renal function. Quality of life and Cost-effectiveness of treatment will be assessed from a UK National Health Service perspective.DISCUSSION: With proven efficacy in removing IgG antibodies and its use as a relatively safe treatment option in a multitude of conditions, immunoadsorption has the potential to offer patients with primary MN a more directed therapy free from the short and long-term side-effects generally seen in this condition.

INTRODUCTION: COVID-19 has spread globally to now be considered a pandemic by the World Health Organisation. Initially patients appeared to have a respiratory limited disease but there are now increasing reports of multiple organ involvement including renal disease in association with COVID-19. We studied the development and outcomes of acute kidney injury (AKI) in patients with COVID-19, in a large multicultural city hospital trust in the UK, to better understand the role renal disease has in the disease process.METHODS: This was a retrospective review using electronic records and laboratory data of adult patients admitted to the four Manchester University Foundation Trust Hospitals between March 10 and April 30 2020 with a diagnosis of COVID-19. Records were reviewed for baseline characteristics, medications, comorbidities, social deprivation index, observations, biochemistry and outcomes including mortality, admission to critical care, mechanical ventilation and the need for renal replacement therapy.RESULTS: There were 1032 patients included in the study of whom 210 (20.3%) had AKI in association with the diagnosis of COVID-19. The overall mortality with AKI was considerably higher at 52.4% compared to 26.3% without AKI (p-value DISCUSSION: We have shown that the development of AKI is associated with dramatically worse outcomes for patients, in both mortality and the requirement for critical care. Patients with COVID-19 presenting with, or at risk of AKI should be closely monitored and appropriately managed to prevent any decline in renal function, given the significant risk of deterioration and death.

Acute kidney injury (AKI) is now widely recognised as a serious health care issue, occurring in up to 25% of hospital in-patients, often with worsening of outcomes. There have been several reports of substandard care in AKI. This quality improvement (QI) programme aimed to improve AKI care and outcomes in a large teaching hospital. Areas of documented poor AKI care were identified and specific improvement activities implemented through sequential Plan-Do-Study-Act (PDSA) cycles. An electronic alert system (e-alert) for AKI was developed, a Priority Care Checklist (PCC) was tested with the aid of specialist nurses whilst targeted education activities were carried out and data on care processes and outcomes monitored. The e-alert had a sensitivity of 99% for the detection of new cases of AKI. Key aspects of the PCC saw significant improvements in their attainment: Detection of AKI within 24 hours from 53% to 100%, fluid assessment from 42% to 90%, drug review 48% to 95% and adherence to nine key aspects of care from 40% to 90%. There was a significant reduction in variability of delivered AKI care. AKI incidence reduced from 9% of all hospitalisations at baseline to 6.5% (28% reduction), AKI related length of stay reduced from 22.1 days to 17 days (23% reduction) and time to recovery (AKI days) 15.5 to 9.8 days (36% reduction). AKI related deaths also showed a trend towards reduction, from an average of 38 deaths to 34 (10.5%). The number of cases of hospital acquired AKI were reduced by 28% from 120 to 86 per month. This study demonstrates significant improvements related to a QI programme combining e-alerts, a checklist implemented by a nurse and education in improving key processes of care. This resulted in sustained improvement in key patient outcomes.

Clear national and trust guidelines are available regarding the management of patients receiving anticoagulation therapy (warfarin and low molecular weight heparin (LMWH)). Lack of available evidence for LMWH in renal impairment makes anti-factor Xa monitoring crucial in this population. Two