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A dose response study of the effect of an octapeptide somatostatin analogue, SMS 201-995, on meal stimulated gastric acid secretion was carried out in 12 healthy volunteers. Infusion of SMS 201-995 in a dose of 50 pmol/kg/h almost completely abolished the acid response to the meal. Pl-gastrin was significantly decreased during infusion of 10 pmol/kg/h of SMS 201-995 and insulin was significantly inhibited during infusion of 50 pmol/kg/h. SMS 201-995 in a dose of 50 pmol/kg/h inhibited basal and submaximal pentagastrin stimulated acid secretion by 77% and 84% respectively (p less than 0.01). On a molar basis SMS 201-995 is substantially more potent than natural somatostatin in inhibiting gastric acid secretion. [ABSTRACT FROM PUBLISHER]

The effect of low dose infusions of somatostatin on meal stimulated gastric acid secretion was studied in eight healthy volunteers by intragastric titration after a peptone test meal with radioimmunoassay control of the plasma concentrations of somatostatin and the pancreatic hormones glucagon and insulin. Infusion of somatostatin in a dose of 100 ng/kg/h, resulting in a plasma concentration of 13.4 +/- 2.1 pmol/l, inhibited acid secretion significantly, and in a dose of 800 ng/kg/h, with corresponding plasma concentration of 66.5 +/- 12.0 pmol/l the acid secretion was virtually abolished. Plasma concentrations of insulin and pancreatic glucagon decreased significantly during infusion of 200 ng/kg/h (24.5 +/- 7.5 pmol/l) and glucose concentrations increased. Serum gastrin was only significantly decreased during the highest dose of somatostatin. The range of plasma somatostatin concentrations obtained with the lower doses correspond to reported physiological variations. The results support the concept that somatostatin participates in the hormonal control of the pancreatic endocrine and the acid secretion. [ABSTRACT FROM PUBLISHER]

The effect of endogenous pancreatic glucagon on submaximal pentagastrin stimulated gastric acid secretion was studied by infusion of 1-arginine in patients with duodenal ulcer before and after parietal cell vagotomy without drainage (PCV). Preoperatively infusion of 1-arginine resulted in a marked inhibition of acid secretion, whereas no effect was found postoperatively. Plasma glucagon concentrations were identical pre- and postoperatively, fasting as well as during arginine infusion. Serum gastrin concentration rose after PCV but not unaffected by arginine infusion both pre- and postoperatively. The study demonstrates that intact vagal innervation of the fundic glands is a condition of inhibition of pentagastrin induced acid secretion by pancreatic glucagon released by infusion of 1-arginine. [ABSTRACT FROM PUBLISHER]

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Historically, it takes an average of 17 years to move new treatments from clinical evidence to daily practice. Given the highly effective treatments now available to prevent or delay kidney disease onset and progression, this is far too long. The time is now to narrow the gap between what we know and what we do. Clear guidelines exist for the prevention and management of common risk factors for kidney disease, such as hypertension and diabetes, but only a fraction of people with these conditions worldwide are diagnosed, and even fewer are treated to target. Similarly, the vast majority of people living with kidney disease are unaware of their condition, because in the early stages it is often silent. Even among patients who have been diagnosed, many do not receive appropriate treatment for kidney disease. Considering the serious consequences of kidney disease progression, kidney failure, or death, it is imperative that treatments are initiated early and appropriately. Opportunities to diagnose and treat kidney disease early must be maximized beginning at the primary care level. Many systematic barriers exist, ranging from patient to clinician to health systems to societal factors. To preserve and improve kidney health for everyone everywhere, each of these barriers must be acknowledged so that sustainable solutions are developed and implemented without further delay., (Copyright © 2024 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK., Methods: With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR)., Results: Among the 2367 kidney patients treated with sotrovimab ( n  = 1852) or molnupiravir ( n  = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17-0.71]; P  = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13-1.21); P  = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P  > .05)., Conclusions: In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves., Competing Interests: B.G. has received research funding from the Laura and John Arnold Foundation, NIHR, NIHR School of Primary Care Research, NHS England, NIHR Oxford Biomedical Research Centre, Mohn–Westlake Foundation, NIHR Applied Research Collaboration Oxford and Thames Valley, Wellcome Trust, Good Thinking Foundation, Health Data Research UK, Health Foundation, World Health Organization, UKRI MRC, Asthma UK, British Lung Foundation and the Longitudinal Health and Wellbeing strand of the National Core Studies programme; he is a non-executive director at NHS Digital; he also receives personal income from speaking and writing for lay audiences on the misuse of science. B.M.K. is employed by NHS England, working on medicines policy and a clinical lead for primary care medicines data. A.M. is a member of RCGP health informatics group and the NHS Digital GP data Professional Advisory Group, and received consulting fee from Induction Healthcare. E.P. was a consultant for WHO SAGE COVID-19 Vaccines Working Group. I.J.D. has received research grants from GSK and AstraZeneca and holds shares in GSK. J.T. was funded by an unrestricted grant from GSK for methodological research unrelated to this work. S.L. received remuneration for medical writing from Kidney Care UK, UK Kidney Association and GORE; support for attending meeting from UK Kidney Association; and is Chair of Patients Council of UK Kidney Association, and Secretary and Trustee of Guy's & St Thomas' Kidney Patients' Association. V.M. received grant from National Institute for Health and Care Research. E.C. is a member of UK Kidney Association Infection Prevention & Control committee. F.L. received grants to institution from AstraZeneca, Pfizer, Novartis, and payment to institution from AstraZeneca for scientific events. S.B. received consulting fees from GSK and AstraZeneca. D.N. received grants from National Institute for Health and Care Research, MRC and GSK Open Lab, unrelated to this work; and is the UKKA Director of Informatics Research. L.A.T. has received research funding from MRC, Wellcome, NIHR and GSK, consulted for Bayer in relation to an observational study of chronic kidney disease (unpaid), and is a member of 4 non-industry funded (NIHR/MRC) trial advisory committees (unpaid) and MHRA Expert advisory group (Women's Health). The other authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric and social care) and physical rehabilitation management is variable across England, as well as the rest of the UK. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The National Health Service (NHS) England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK., Methods: A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD., Results: Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (>80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the 'Systems' section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic wellbeing assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking Therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognize psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services., Conclusion: There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the 'Systems' section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD., Competing Interests: The results presented in this article have not been published previously in whole or part. There are no reported conflicts of interest for any authors., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England., Methods: With the approval of NHS England, we performed a retrospective cohort study among people with moderate-to-severe kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3-5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ-AZ vs BNT-BNT) and three-dose (AZ-AZ-BNT vs BNT-BNT-BNT) schedules., Findings: After two doses, incidence during the Delta wave was higher in AZ-AZ (n = 257,580) than BNT-BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n = 220,330) and BNT-BNT-BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance., Interpretation: Among individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations., Funding: National Core Studies, Wellcome Trust, MRC, and Health Data Research UK., Competing Interests: EPKP has been employed as a consultant by the WHO Strategic Advisory Group of Experts on Immunization Working Group on COVID-19 Vaccines. WJH and VM have received research funding from the National Institute for Health and Care Research (NIHR). EJC has received research funding (paid to the institution) form Kidney Research UK and partner charities and patient associations. FL is employed as Policy Director of Kidney Care UK, which has received funding from AstraZeneca, Pfizer, Novartis, and GSK, and honoraria (paid to the institution) from AstraZeneca, Novartis, and University College London for invited talks and meeting attendance. FL is Lay Chair of the West Herts Hospital Organ Donation committee; Vice Chair of the Lister Hospital Kidney Patients’ Association; and member of the International Society for Nephrology patient liaison advisory group. SL has received medical writing fees from the UK Kidney Association and Vascular Society of Great Britain and Ireland; freelance employment as Deputy Editor for Kidney Care UK's Kidney Matters magazine; and support for conference attendance from the UK Kidney Association. SL is Chair of the UK Kidney Association Patient Council and member of the Guy’s and St Thomas’ Kidney Patients’ Association. BMK is also employed by NHS England as a specialist pharmacist adviser. AM has received consultancy fees from Induction Healthcare and is a member of the Royal College of General Practitioners’ health informatics group and the NHS Digital GP data Professional Advisory Group. BG’s work on better use of data in healthcare more broadly is currently funded in part by: the Bennett Foundation, the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all Bennett Institute staff are supported by BG’s grants on this work. BG is a Non-Executive Director at NHS Digital. DN is the UK Kidney Association's Director of Informatics Research. LAT has received research funding from the Medical Research Council (MRC), Wellcome, and NIHR; has consulted for Bayer in relation to an observational study of chronic kidney disease (unpaid); is a member of four non-industry funded (NIHR/MRC) trial advisory committees (unpaid); and is a member of the Medicines and Healthcare products Regulatory Agency expert advisory group (Women’s Health). The authors disclose no other competing interests., (© 2023 The Authors.)

Objective: To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England., Design: Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England., Setting: Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR)., Participants: A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR., Main Outcome Measures: Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models., Results: 992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake., Conclusion: Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study., Competing Interests: Competing interests: BG’s work on better use of data in healthcare more broadly is currently funded in part by: the Bennett Foundation, the Wellcome Trust, NIHR Oxford Biomedical Research Centre, NIHR Applied Research Collaboration Oxford and Thames Valley, the Mohn-Westlake Foundation; all Bennett Institute staff are supported by BG's grants on this work. BG is a Non-Executive Director at NHS Digital. EJW holds grants from MRC., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Life participation is an outcome of critical importance to patients receiving peritoneal dialysis (PD). However, there is no widely accepted or validated tool for measuring life participation in patients receiving PD., Methods: Online consensus workshop to identify the essential characteristics of life participation as a core outcome, with the goal of establishing a patient-reported outcome measure for use in all trials in patients receiving PD. Thematic analysis of transcripts was performed., Results: Fifty-six participants, including 17 patients and caregivers, from 15 countries convened via online videoconference. Four themes were identified: reconfiguring expectations of daily living (accepting day-to-day fluctuation as the norm, shifting thresholds of acceptability, preserving gains in flexibility and freedom), ensuring broad applicability and interpretability (establishing cross-cultural relevance, incorporating valued activities, distinguishing unmodifiable barriers to life participation), capturing transitions between modalities and how they affect life participation (responsive to trajectory towards stable, reflecting changes with dialysis transitions) and maximising feasibility of implementation (reducing completion burden, administrable with ease and flexibility)., Conclusions: There is a need for a validated, generalisable outcome measure for life participation in patients receiving PD. Feasibility, including length of time to complete and flexible mode of delivery, are important to allow implementation in all trials that include patients receiving PD.

Objective: To examine the association between practice percentage coding of chronic kidney disease (CKD) in primary care with risk of subsequent hospitalisations and death., Design: Retrospective cohort study using linked electronic healthcare records., Setting: 637 general practitioner (GP) practices in England., Participants: 167 208 patients with CKD stages 3-5 identified by 2 measures of estimated glomerular filtration rate <60 mL/min/1.73 m 2 , separated by at least 90 days, excluding those with coded initiation of renal replacement therapy., Main Outcome Measures: Hospitalisations with cardiovascular (CV) events, heart failure (HF), acute kidney injury (AKI) and all-cause mortality RESULTS: Participants were followed for (median) 3.8 years for hospital outcomes and 4.3 years for deaths. Rates of hospitalisations with CV events and HF were lower in practices with higher percentage CKD coding. Trends of a small reduction in AKI but no substantial change in rate of deaths were also observed as CKD coding increased. Compared with patients in the median performing practice (74% coded), patients in practices coding 55% of CKD cases had a higher rate of CV hospitalisations (HR 1.061 (95% CI 1.015 to 1.109)) and HF hospitalisations (HR 1.097 (95% CI 1.013 to 1.187)) and patients in practices coding 88% of CKD cases had a reduced rate of CV hospitalisations (HR 0.957 (95% CI 0.920 to 0.996)) and HF hospitalisations (HR 0.918 (95% CI 0.855 to 0.985)). We estimate that 9.0% of CV hospitalisations and 16.0% of HF hospitalisations could be prevented by improving practice CKD coding from 55% to 88%. Prescription of antihypertensives was the most dominant predictor of a reduction in hospitalisation rates for patients with CKD, followed by albuminuria testing and use of statins., Conclusions: Higher levels of CKD coding by GP practices were associated with lower rates of CV and HF events, which may be driven by increased use of antihypertensives and regular albuminuria testing, although residual confounding cannot be ruled out., Competing Interests: Competing interests: David C Wheeler has an ongoing consultancy contract with AstraZeneca and has received honoraria, consultancy fees or speaker fees from Amgen, Astellas, Bayer, Boehringer Ingelheim, GlaxoSmithKline, Gilead, Janssen, Napp/Mundipharma, Merck Sharp and Dohme, Tricida, Vifor and Zydus. David Adlam has received research funding from Abbott vascular to support a clinical research fellow; he has also received funding from AstraZeneca inc. for unrelated research and has undertaken consultancy for General Electric inc. to support research funds. Dorothea Nitsch reports grants unrelated to this work from the National Institute for Health Research, Medical Research Council (MRC), the Health Foundation and GlaxoSmithKline., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Competing Interests: Competing interests: Michelle Willicombe has received study support from Oxford Immunotec and is primary investigator for the MELODY study, which received funding from MRC, Kidney Research UK, Vasculitis UK, Blood Cancer UK, and the Cystic Fibrosis Trust. Kidney Care UK has received advisory fees for Fiona Loud’s time from Otsuka (home dialysis), Baxter (patient education), AstraZeneca (on CKD plus one on covid), and Novartis (leadership). Liz Lightstone has received fees for consultancies /advisories for Alexion, AstraZeneca, BMS, Biogen, GSK, Kezar, Novartis, and Pfizer, and been part of speaker bureaux for Alexion and GSK.

This article describes a pathway for collaboration between transplant healthcare professionals and organ recipients. Under the umbrella of the European Society for Organ Transplantation (ESOT) a joint initiative started from three Sections and Committees of ESOT: EDTCO (European Donation and Transplant Coordination Organisation), ETHAP (European Transplant Allied Healthcare Professionals) and ELPAT (Ethical, Legal and Psycho-social Aspects of Transplantation). The formal 'kick-off' of the Advisory Board Meeting of the European Transplant Patient Organisation (ETPO) was during the ESOT congress in 2019. The aim was to produce a series of statements to serve as a path to dialogue between patients and transplant professionals and to define the next steps towards giving a voice to the patient network. To include the patients' perspectives, two surveys have been performed. The results identified the unmet needs and lead to a proposal for future plans. Educational activities have since started leading to a patient learning workstream. All initiatives taken have one purpose: to include patients, give them a voice and build a foundation for collaboration between patients and transplant professionals. ESOT has created a platform for mutual understanding, learning and a collaborative partnership between ETPO and European donation and transplant professionals., (© 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Background: Patients receiving peritoneal dialysis (PD) endure an ongoing regimen of daily fluid exchanges and are at risk of potentially life-threatening complications and debilitating symptoms that can limit their ability to participate in life activities. The aim of the study was to identify the characteristics, content and psychometric properties of measures for life participation used in research in PD., Methods: We searched MEDLINE, Embase, PsychInfo, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane Central Register of Controlled Trials from inception to May 2020 for all studies that reported life participation in patients on PD. The characteristics, dimensions of life participation and psychometric properties of these measures were extracted and analyzed., Results: Of the 301 studies included, 17 (6%) were randomized studies and 284 (94%) were nonrandomized studies. Forty-two different measures were used to assess life participation. Of these, 23 (55%) were used in only one study. Fifteen (36%) measures were specifically designed to assess life participation, while 27 (64%) measures assessed broader constructs, such as quality of life, but included questions on life participation. The 36-Item Short Form Health Survey and Kidney Disease Quality of Life Short Form were the most frequently used measures [122 (41%) and 86 (29%) studies, respectively]. Eight (19%) measures had validation data to support their use in patients on PD., Conclusions: The many measures currently used to assess life participation in patients receiving PD vary in their characteristics, content and validation. Further work to pilot and validate potential measures is required to establish a core patient-reported outcome measure to assess life participation in patients receiving PD., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Kidney transplantation offers better outcomes and quality of life at lower societal costs compared with other options of renal replacement therapy. In this review of the European Kidney Health Alliance, the current status of kidney transplantation throughout Europe and suggestions for improvement of transplantation rates are reported. Although the European Union (EU) has made considerable efforts in the previous decade to stimulate transplantation activity, the discrepancies among European countries suggest that there is still room for improvement. The EU efforts have partially been neutralized by external factors such as economic crises or legal issues, especially the illicit manipulation of waiting lists. Hence, growth in the application of transplantation throughout Europe virtually remained unchanged over the last few years. Continued efforts are warranted to further stimulate transplantation rates, along with the current registration and data analysis efforts supported by the EU in the Effect of Differing Kidney Disease Treatment Modalities and Organ Donation and Transplantation Practices on Health Expenditure and Patient Outcomes project. Future actions should concentrate on organization, harmonization and improvement of the legal consent framework, population education and financial stimuli., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

The promise of personalized medicine to deliver "the right treatments at the right time to the right person" is the next frontier in healthcare. However, to implement personalized medicine in chronic diseases such as diabetes mellitus and diabetic kidney disease (DKD), a number of different aspects need to be taken into account. Better risk stratification and more precise options for treatment need to be developed and included in clinical practice guidelines. A patient's unique psychological, social and environmental situation also drive disease progression and outcomes. Appraising the cost effectiveness of precision medicines is necessary, not just as the cost of new therapies, but also the cost of diagnosis with novel methodologies and averted complications. As the prevalence of DKD grows worldwide to epidemic proportions, challenges such as global disparities in resources, access to healthcare and prevalence need to be addressed. This review considers these issues to achieve the short and longer-term goals of implementing personalized medicine in clinical practice., (© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: It has been suggested that the research priorities of those funding and performing research in transplantation may differ from those of end service users such as patients, carers and healthcare professionals involved in day-to-day care. The Kidney Transplant Priority Setting Partnership (PSP) was established with the aim of involving all stakeholders in prioritising future research in the field., Methods: The PSP methodology is as outlined by the James Lind Alliance. An initial survey collected unanswered research questions from patients, carers and clinicians. Duplicate and out-of-scope topics were excluded and the existing literature searched to identify topics answered by current evidence. An interim prioritisation survey asked patients and professionals to score the importance of the remaining questions to create a ranked long-list. These were considered at a final consensus workshop using a modified nominal group technique to agree a final top ten., Results: The initial survey identified 497 questions from 183 respondents, covering all aspects of transplantation from assessment through to long-term follow-up. These were grouped into 90 unanswered "indicative" questions. The interim prioritisation survey received 256 responses (34.8% patients/carers, 10.9% donors and 54.3% professionals), resulting in a ranked list of 25 questions that were considered during the final workshop. Participants agreed a top ten priorities for future research that included optimisation of immunosuppression (improved monitoring, choice of regimen, personalisation), prevention of sensitisation and transplanting the sensitised patient, management of antibody-mediated rejection, long-term risks to live donors, methods of organ preservation, induction of tolerance and bioengineering of organs. There was evidence that patient and carer involvement had a significant impact on shaping the final priorities., Conclusions: The final list of priorities relates to all stages of the transplant process, including access to transplantation, living donation, organ preservation, post-transplant care and management of the failing transplant. This list of priorities will provide an invaluable resource for researchers and funders to direct future activity., Competing Interests: Angela Beale, William Beale, Leanne Metcalf, Keith Hodkinson, Peter Morris and Katriona O’Donoghue have no conflicts of interest to declare. Simon Knight has received consultancy fees from OrganOx UK Ltd. Lorna Marson has received lecture fees from Astellas and Novartis. Fiona Loud has received consultancy fees from Merck and Galderma. Graham Lipkin has received lecture fees from Raptor Pharmaceuticals and consulting fees from Alexion Pharma. Rachel Hilton has received lecture fees from Roche Pharmaceuticals and consultancy fees from Novartis. Simon Ball has received research grants from Oxfod Immunotec Ltd. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Objectives: Conservative kidney management (CKM) has been developed in the United Kingdom (UK) as an alternative to dialysis for older patients with stage 5 CKD (CKD5) and multiple comorbidities. This national survey sought to describe the current scale and pattern of delivery of conservative care in UK renal units and identify their priorities for its future development., Design, Setting, Participants, & Measurements: A survey on practice patterns of CKM for patients age 75 and older with CKD5 was sent to clinical directors of all 71 adult renal units in the UK in March 2013., Results: Sixty-seven units (94%) responded. All but one unit reported providing CKM for some patients. Terminology varied, although "conservative management" was the most frequently used term (46%). Lack of an agreed-upon definition of when a patient is receiving CKM made it difficult to obtain meaningful data on the numbers of such patients. Fifty-two percent provided the number of CKM patients age ≥ 75 years in 2012; the median was 45 per unit (interquartile range [IQR], 20-83). The median number of symptomatic CKM patients who would otherwise have started dialysis was eight (IQR, 4.5-22). CKM practice patterns varied: 35% had a written guideline, 23% had dedicated CKM clinics, 45% had dedicated staff, and 50% provided staff training on CKM. Most units (88%) provided primary care clinicians with information/advice regarding CKM. Eighty percent identified a need for better evidence comparing outcomes on CKM versus dialysis, and 65% considered it appropriate to enter patients into a randomized trial., Conclusions: CKM is provided in almost all UK renal units, but scale and organization vary widely. Lack of common terminology and definitions hinders the development and assessment of CKM. Many survey respondents expressed support for further research comparing outcomes with conservative care versus dialysis., (Copyright © 2015 by the American Society of Nephrology.)

Background: Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations., Methods/design: Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components: 1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline., Discussion: The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice., Trial Registration: ISRCTN42955626.

Background: This paper explores how a group of people with renal or other vascular conditions collaborated with renal practitioners in undertaking a quality improvement project, the aim of which was to reduce variation in care for people with Stages 3-4 chronic kidney disease., Development and Role of the Group: The patient advisory group supporting the project took a decisive and leading role in the creation of self-management materials and subsequent training for healthcare professionals and patients. The role of the patient advisory group was evaluated informally throughout the project. Confidence amongst the patient advisory group members grew as the project developed., Conclusion: Clinicians are often unclear on how to involve patients and carers in quality improvement projects, yet it is increasingly recognised as important. In practice, patients with experience of long-term conditions can co-lead quality improvement projects. It is recommended that further evaluation of the role of advisory groups is warranted., (© 2013 European Dialysis and Transplant Nurses Association/European Renal Care Association.)

Cysteamine in a single subcutaneous administration induces release of gastrin, acid hypersecretion, and duodenal ulcer in rats. Pentagastrin-induced acid hypersecretion has no ulcerogenic effect. The Brunner glands in the proximal duodenum have previously been shown to be an important factor in the natural defence of the duodenal mucosa, and this study has been performed to determine the effect of cysteamine and pentagastrin on the Brunner glands in the rat. The proximal duodenum was isolated in situ and drained by a polyethylene tube. The secretion was studied for two 5-h periods after administration of cysteamine or pentagastrin, and then the Brunner glands were studied histologically. Pentagastrin did not affect spontaneous Brunner gland secretion, whereas cysteamine inhibited the output approximately 50%. After cysteamine the secretory cells were low and depleted of mucus, suggesting that cysteamine interferes with the synthesis of the secretory product. The depression of the Brunner gland secretion may be an important factor in the pathogenesis of cysteamine-induced duodenal ulceration.

Biopsies from the fundic gastric mucosa of eight human subjects were extracted with acid-ethanol and analyzed for somatostatin- and glucagon-like immunoreactivity using region-specific RIAs. Five extracts were studied by gel filtration. The glucagon content was close to the detection limit in all extracts, and none of the known glucagon components could be identified by gel filtration. The concentration of somatostatin-like immunoreactivity was 17.4 +/- 2.0 pmol/g wet wt, and the immunoreactivity was distributed among four well defined peaks, two of which corresponded to somatostatin 1-14 and 1-28, respectively.

A prospective, randomized, controlled trial was conducted to compare truncal vagotomy and drainage (TV), selective vagotomy and drainage (SV) and parietal cell vagotomy (PCV) as elective treatment for duodenal ulcer. Between 11 and 15 years after operation, 248 patients were available for study of the recurrent ulceration rate by a life table method, and 197 patients could be studied with regard to postvagotomy symptoms. The recurrent ulcer rates were 28.5% for TV, 37.4% for SV, and 39.3% for PCV. These differences were not statistically significant. The incidence of severe postvagotomy symptoms was as follows: dyspepsia, 18.4% for TV, 20.5% for SV, 8.6% for PCV; dumping, 5.9% for TV, 19.6% for SV, 2.2% for PCV; diarrhea, 9.8% for TV, 11.8% for SV, 4.4% for PCV. The incidence of severe dumping was significantly less frequent among the PCV patients than the SV group. The differences did not reach statistical significance in any of the other groups. There was no significant difference in the Visick gradings among the three groups either before or after treatment of the failures. About two thirds of the patients in each group were finally satisfied with their operation, often after second operations or prolonged medical treatment. It is concluded that none of the three forms of vagotomy can be recommended as the standard operative treatment of duodenal ulceration.