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Objective Sodium-glucose cotransporter-2 inhibitors (SGLT2Is) reduce cardio-metabolic and renal outcomes in patients with type 2 diabetes (T2D) but their efficacy and safety in older or frail individuals remains unclear. Methods We searched PubMed, Scopus, Web of Science, Cochrane CENTRA and Google Scholar and selected randomised controlled trials and observational studies comparing SGLT2Is versus placebo/other glucose-lowering agent for people with frailty or older individuals (>65 years) with T2D and heart failure (HF). Extracted data on the change in HbA1c % and safety outcomes were pooled in a random-effects meta-analysis model. Results We included data from 20 studies (22 reports; N  = 77,083 patients). SGLT2Is did not significantly reduce HbA1c level (mean difference −0.13, 95%CI: −0.41 to 0.14). SGLT2Is were associated with a significant reduction in the risk of all-cause mortality (risk ratio (RR) 0.81, 95%CI: −0.69 to 0.95), cardiac death (RR 0.80, 95%CI: −0.94 to 0.69) and hospitalisation for heart failure (HHF) (RR 0.69, 95%CI: 0.59–0.81). However, SGLT2Is did not demonstrate significant effect in reducing in the risk of macrovascular events (acute coronary syndrome or cerebral vascular occlusion), renal progression/composite renal endpoint, acute kidney injury, worsening HF, atrial fibrillation or diabetic ketoacidosis. Conclusions In older or frail patients with T2D and HF, SGLT2Is are consistently linked with a decrease in total mortality and the overall burden of cardiovascular (CV) events, including HHF events and cardiac death, but not protective for macrovascular death or renal events. Adverse events were more difficult to quantify but the risk of diabetic ketoacidosis or acute kidney injury was not significantly increase. [ABSTRACT FROM AUTHOR]

Understanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Providing holistic care to kidney patients is important; however, without full consideration of the perspectives of people living with a kidney transplant, the provision of truly 'holistic healthcare' cannot be possible. It is imperative to understand patient experiences by including kidney patients in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support, impacting overall health. The aim of this study was to develop an in-depth understanding of the lived experiences of kidney transplant recipients. Methods: A total of 23 participants were recruited between two regional nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews were undertaken. Interviews were digitally recorded, transcribed verbatim, and subjected to interpretative phenomenological analysis. Results: Two themes emerged: "managing ongoing fears of dialysis, distress, and COVID-19" and "dealing with difficult conversations". Conclusions: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multidomain experiences that these participants experience will help healthcare professionals to recognize the needs of this group and ensure more responsive psychosocial care. [ABSTRACT FROM AUTHOR]

Summary: Zoledronate could be contributing to the development of acute kidney injury in a small number of patients. Since estimated glomerular function (eGFR) is simpler to obtain and at least as good a predictor as creatinine clearance (CrCl), it should be used in everyday practice. Introduction: Zoledronate is widely used for the treatment of osteoporosis. A potential side effect is acute kidney injury (AKI). Advice from the UK Medicines and Healthcare products Regulatory Agency (MHRA) in 2019 stated that CrCl and not estimated glomerular filtration rate (eGFR) should be used and that treatment should not be given if CrCl < 35 ml/min. The objective of this study was to compare our current method of assessing renal function (eGFR) with the method proposed by the MHRA (CrCl) for predicting AKI after zoledronate infusions. Methods: The evaluation was performed at the Metabolic Bone Centre in Sheffield Teaching Hospitals, UK. Data on all the patients who had zoledronate from 1/09/2015 to 1/10/2020 were included. Results: Data on 4405 patients were retrieved (total number of infusions 7660). Creatinine in the 14 days post-infusion was available for a total of 969 infusions and AKI was observed within 14 days following 45 infusions (4.6%). One patient died due to pneumonia. One patient needed continued haemodialysis. Severe AKI (threefold in creatinine and/or eGFR < 15 ml/min/173 m2) was observed within 1 year following 24 infusions. If the MHRA recommendations had been followed, 996 infusions with baseline CrCl < 35 ml/min would not have been given. Of these, follow-up data on serum creatinine within 14 days were available for 142 infusions, showing AKI in only four (2.8%). Logistic regression showed that both CrCl and eGFR were significant factors in predicting AKI within 14 days, but that the current recommended cut-off of CrCl 35 ml/min had poor sensitivity. Conclusion: Since eGFR is at least as good a predictor of AKI as CrCl, and permits the treatment of more patients at high fracture risk, we recommend that eGFR is used to determine renal function for zoledronate treatment. We suggest that the infusion is given over 30 min in patients with eGFR < 50 ml/min/1.73 m2. [ABSTRACT FROM AUTHOR]

Background and aims: An observational association between nonalcoholic fatty liver disease (NAFLD) and kidney function impairment has been reported. We aimed to investigate the causal effects from NAFLD on estimated glomerular filtration rate (eGFR) by a Mendelian randomization (MR) study. Methods: We first performed single‐variant MR with rs738409 as a genetic instrument for NAFLD. Another genetic instrument was developed from a genome‐wide association study for biopsy‐confirmed NAFLD among individuals of European ancestry (1483 cases and 17 781 controls). The eGFR outcome was assessed in individuals of white British ancestry from the UK Biobank (N = 321 405). The associations were reassessed in the negative control subgroup (body mass index < 30 kg/m2, absence of central obesity, and serum alanine aminotransferase level ≤ 20 IU/mL) with a low probability of developing NAFLD. As a replication analysis, a summary‐level MR was performed with the European ancestry CKDGen dataset (N = 567 460). Results: In the UK Biobank, a genetic predisposition for NAFLD, determined either by the single SNP rs738409 or by the group of variants, was significantly associated with a reduced eGFR even with adjustment for metabolic disorders. Although the associations were not significant in the negative control subgroup with a low probability of developing NAFLD, they were significant in the subgroup with a remaining risk of NAFLD, suggesting the absence of a horizontal pleiotropic pathway. The summary‐level MR from the CKDGen dataset supported the causal effects of NAFLD on reduced eGFR. Conclusions: This MR analysis supports the causal reduction in kidney function by NAFLD. [ABSTRACT FROM AUTHOR]

Background: Previous observational studies suggested that a reduction in estimated glomerular filtration rate (eGFR) or a supranormal eGFR value was associated with adverse cardiovascular risks. However, a previous Mendelian randomization (MR) study under the linearity assumption reported null causal effects from eGFR on myocardial infarction (MI) risks. Further investigation of the nonlinear causal effect of kidney function assessed by eGFR on the risk of MI by nonlinear MR analysis is warranted.Methods: In this MR study, genetic instruments for log-eGFR based on serum creatinine were developed from European samples included in the CKDGen genome-wide association study (GWAS) meta-analysis (N=567,460). Alternate instruments for log-eGFR based on cystatin C were developed from a GWAS of European individuals that included the CKDGen and UK Biobank data (N=460,826). Nonlinear MR analysis for the risk of MI was performed using the fractional polynomial method and the piecewise linear method on data from individuals of white British ancestry in the UK Biobank (N=321,024, with 12,205 MI cases).Results: Nonlinear MR analysis demonstrated a U-shaped (quadratic P value < 0.001) association between MI risk and genetically predicted eGFR (creatinine) values, as MI risk increased as eGFR declined in the low eGFR range and the risk increased as eGFR increased in the high eGFR range. The results were similar even after adjustment for clinical covariates, such as blood pressure, diabetes mellitus, dyslipidemia, or urine microalbumin levels, or when genetically predicted eGFR (cystatin C) was included as the exposure.Conclusion: Genetically predicted eGFR is significantly associated with the risk of MI with a parabolic shape, suggesting that kidney function impairment, either by reduced or supranormal eGFR, may be causally linked to a higher MI risk. [ABSTRACT FROM AUTHOR]

Background: Transplantation is widely considered the gold standard method of kidney replacement therapy. Despite compelling evidence for biological sexual dimorphisms, the role of donor and recipient sex matching in transplantation is undefined. Methods: The UK historical cohort study explores the impact of donor and recipient sex on allograft survival, in children receiving their first deceased donor transplant. Nationwide registry data were collected for 1316 transplant procedures performed from January 1, 1999, to December 31, 2019. Results: Male donor–male recipient transplantation occurred most frequently (35%), followed by female donor–male recipient (23%), male donor–female recipient (22%), and female donor–female recipient (20%). The median follow-up time was 7.03 years (IQR: 2.89–12.4 years), with a total of 10,326 person-years. Male donor–male recipients were associated with the highest 10-year kidney allograft survival (72.8% [95% CI 68.3–77.8]) and male donor–female recipients with the lowest (64% [95% CI 57.7–71.1]). Multivariable Cox regression demonstrated for male donor transplantation, the risk of kidney allograft failure was 1.46 times greater for female (compared to male) recipients, after adjusting for acquired recipient age, recipient/donor age at transplantation, mismatched HLA A/B/DR, waitlist time, cold ischemia time, CMV seropositivity, donor hypertension, and donor diabetes (HR 1.46 [95% CI. 1.06–2.01], p = 0.02). There was no evidence for an independent effect of donor or recipient sex in other combinations. Conclusion: This study highlights the complex relationship between donor and recipient sex and pediatric kidney allograft survival, which require further mechanistic evaluation. [ABSTRACT FROM AUTHOR]

Background: Estimation of glomerular filtration rate using equations based on creatinine is widely used to manage chronic kidney disease. In the UK, the Chronic Kidney Disease Epidemiology Collaboration creatinine equation is recommended. Other published equations using cystatin C, an alternative marker of kidney function, have not gained widespread clinical acceptance. Given higher cost of cystatin C, its clinical utility should be validated before widespread introduction into the NHS., Objectives: Primary objectives were to: (1) compare accuracy of glomerular filtration rate equations at baseline and longitudinally in people with stage 3 chronic kidney disease, and test whether accuracy is affected by ethnicity, diabetes, albuminuria and other characteristics; (2) establish the reference change value for significant glomerular filtration rate changes; (3) model disease progression; and (4) explore comparative cost-effectiveness of kidney disease monitoring strategies., Design: A longitudinal, prospective study was designed to: (1) assess accuracy of glomerular filtration rate equations at baseline ( n  = 1167) and their ability to detect change over 3 years ( n  = 875); (2) model disease progression predictors in 278 individuals who received additional measurements; (3) quantify glomerular filtration rate variability components ( n  = 20); and (4) develop a measurement model analysis to compare different monitoring strategy costs ( n  = 875)., Setting: Primary, secondary and tertiary care., Participants: Adults (≥ 18 years) with stage 3 chronic kidney disease., Interventions: Estimated glomerular filtration rate using the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations., Main Outcome Measures: Measured glomerular filtration rate was the reference against which estimating equations were compared with accuracy being expressed as P30 (percentage of values within 30% of reference) and progression (variously defined) studied as sensitivity/specificity. A regression model of disease progression was developed and differences for risk factors estimated. Biological variation components were measured and the reference change value calculated. Comparative costs of monitoring with different estimating equations modelled over 10 years were calculated., Results: Accuracy (P30) of all equations was ≥ 89.5%: the combined creatinine-cystatin equation (94.9%) was superior ( p  < 0.001) to other equations. Within each equation, no differences in P30 were seen across categories of age, gender, diabetes, albuminuria, body mass index, kidney function level and ethnicity. All equations showed poor (< 63%) sensitivity for detecting patients showing kidney function decline crossing clinically significant thresholds (e.g. a 25% decline in function). Consequently, the additional cost of monitoring kidney function annually using a cystatin C-based equation could not be justified (incremental cost per patient over 10 years = £43.32). Modelling data showed association between higher albuminuria and faster decline in measured and creatinine-estimated glomerular filtration rate. Reference change values for measured glomerular filtration rate (%, positive/negative) were 21.5/-17.7, with lower reference change values for estimated glomerular filtration rate., Limitations: Recruitment of people from South Asian and African-Caribbean backgrounds was below the study target., Future Work: Prospective studies of the value of cystatin C as a risk marker in chronic kidney disease should be undertaken., Conclusions: Inclusion of cystatin C in glomerular filtration rate-estimating equations marginally improved accuracy but not detection of disease progression. Our data do not support cystatin C use for monitoring of glomerular filtration rate in stage 3 chronic kidney disease., Trial Registration: This trial is registered as ISRCTN42955626., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/103/01) and is published in full in Health Technology Assessment ; Vol. 28, No. 35. See the NIHR Funding and Awards website for further award information.

The phenotypic impact of genetic variation of repetitive features in the human genome is currently understudied. One such feature is the multi-copy 47S ribosomal DNA (rDNA) that codes for rRNA components of the ribosome. Here, we present an analysis of rDNA copy number (CN) variation in the UK Biobank (UKB). From the first release of UKB whole-genome sequencing (WGS) data, a discovery analysis in White British individuals reveals that rDNA CN associates with altered counts of specific blood cell subtypes, such as neutrophils, and with the estimated glomerular filtration rate, a marker of kidney function. Similar trends are observed in other ancestries. A range of analyses argue against reverse causality or common confounder effects, and all core results replicate in the second UKB WGS release. Our work demonstrates that rDNA CN is a genetic influence on trait variance in humans., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: The causal nature of the observed associations between serum lipids and apolipoproteins and kidney function are unclear.Methods: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by the glomerular-filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys) and the urinary albumin-to-creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n = 331 368) and UK Biobank (n = 441 016), respectively, and kidney-function markers from the Trøndelag Health Study (HUNT; n = 69 736) and UK Biobank (n = 464 207). The reverse causal direction was examined using variants associated with kidney-function markers selected from recent genome-wide association studies.Results: There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney-function markers. Some, but inconsistent, evidence suggested a weak association of higher genetically predicted atherogenic lipid levels [indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B] with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels.Conclusion: Our MR estimates suggest that serum lipid and apolipoprotein levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels. [ABSTRACT FROM AUTHOR]

Background: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure., Methods: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m 2 or more to first eGFR of less than 30 mL/min per 1·73 m 2 (the therapeutic trial window)., Findings: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases., Interpretation: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand., Funding: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity., Competing Interests: Declaration of interests ERM reports support for the current manuscript from VHL UK/Ireland and consulting fees from MSD. SM is chair of OxalEurope. MS reports support for the current manuscript from a Medical Research Council UK Precision Medicine programme grant (MR/R013942/1) and consulting fees from Travere Therapeutics. RJC reports support for the current manuscript from Kidney Research UK. JAS reports support for the current manuscript from Kidney Research UK, Northern Counties Kidney Research Fund, and the Medical Research Council UK (all payments to institution). JAS is Academic Vice President of the UK Kidney Association. FWKT reports support from the National Institute for Health and Care Research Imperial Biomedical Centre. DN is the UK Kidney Association Director of Informatics Research. DPG reports support for the current manuscript from St Peter's Trust for Kidney Bladder and Prostate Research, Medical Research Council, Kidney Research UK, Kidney Care UK, and Polycystic Kidney Disease Charity (all payments to institution). DPG chairs the Rare Diseases Committee of the UK Kidney Association and reports fees for consulting and presenting from Novartis, Alexion, Calliditas, Sanofi, Britannia, and Travere. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. Methods: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time‐updated CD4 cell count and HIV RNA measurements. Results: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was −2.08 [95% confidence interval (CI) −2.24, −1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). Conclusions: Significant improvement in eGFR slope was observed in patients who switched from TDF‐ to TAF‐containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF. [ABSTRACT FROM AUTHOR]

Background: Currently very little is known about the perceptions and experiences of kidney transplant recipients from a qualitative perspective. As highlighted by the European Kidney Health Alliance recommendations, providing holistic care to kidney patients is important however this is currently an unmet care need in renal disease. It is imperative to understand patient experiences to ensure that they are included in key strategies and future renal service planning. Ignoring these important patient views means that there is a significant risk of inappropriate renal service provision and lack of adequate support impacting on overall health.Method: A purposive sampling strategy will recruit individuals currently living with a kidney transplant, 6 months to 5 years post-transplant. A maximum of 30 patients will be recruited between two Regional Nephrology units within the United Kingdom via clinical gatekeepers. In-depth interviews will be undertaken with participants living with a kidney transplant across the two sites. Interviews will be digitally-recorded, transcribed verbatim and subjected to interpretative phenomenological analysis.Discussion: Renal healthcare professionals need to understand more than the biological impact of receiving a kidney transplant. Understanding the holistic and multi-domain experiences that these patients experience will help healthcare professionals to recognize the needs of this group and ensure more responsive care. [ABSTRACT FROM AUTHOR]

Aims: To compare the effect of bariatric surgery on renal, chronic kidney disease (CKD) and cardiovascular (CV) outcomes among obese patients with insulin-treated type 2 diabetes (T2D) with and without microalbuminuria (i.e., uACR > 3.0 mg/mmol). Methods: A retrospective cohort study was conducted among 11,125 active patients with T2D from The Health Improvement Network (THIN) database. Propensity score matching (up to 1:6 ratio) was used to identify patients who underwent bariatric surgery (N = 131) with a non-bariatric cohort (N = 579). Follow-up was undertaken for 10 years (6487 person-years) to compare differences in risk of cardiovascular events and in renal outcomes. Results: For the matched cohort at baseline: mean age 52 ± 13 years (60% female); weight 116 ± 25 kg, body mass index (BMI) 41 ± 9kg/m2, estimated glomerular filtration rate (eGFR); 70.4 ± 20 mL/min/1.73 m2, and median albumin-creatinine ratio (uACR) 2.0 mg/mmol (interquartile range (IQR): 0.9–5.2 mg/mmol). Bariatric surgery was associated with a 54% reduction in developing CKD compared to their matched non-bariatric cohort (adjusted hazard ratio [aHR]: 0.46; 95%CI: 0.24–0.85, P = 0.02). Among patients with microalbuminuria at baseline, bariatric surgery was protective against CKD (aHR: 0.42, 95%CI: 0.18–0.99, P = 0.050). eGFR was significantly increased from baseline favouring the bariatric group during 75% of the follow-up time (calculated mean difference between groups: 4.1 mL/min/1.73 m2; P < 0.05), especially at 5-year point (74.2 vs 67.8 mL/min/1.73 m2; P < 0.001). However, no significant change was observed with non-fatal CVD episodes (aHR: 0.36, 95%CI: 0.11–1.13, P = 0.079). Albumin levels were significantly reduced throughout the 2 years following the surgery (3.9 vs 4.1 g/dL, P < 0.001). uACR and total protein levels had little or no statistical association to the intervention. Conclusion: Bariatric surgery may protect patients with diabetes with or without microalbuminuria against the risk of CKD and with a modest protective effect on non-fatal CVD risk. Bariatric surgery is also associated with improvements in overall renal outcomes such as eGFR. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the impact of three early phases of renal dialysis, namely pre-dialysis, starting dialysis, and establishing dialysis, on dyadic relationships. Twenty UK-based dyads (20 male patients and their female partners) participated in semi-structured interviews and discussed the effects of dialysis on themselves and their relationship. Dyadic thematic analysis, facilitated by dyadic-level charting, integrated participants' experiences and enabled identification of patterns across dyads. We found that dialysis had positive and negative influences on identity, social relationships, and mental health, forming the themes: Prioritizing the Patient, Carrying the Burden, and Changing Identities. The final theme, Managing the Relationship, described how dyads prevented dialysis from negatively impacting their relationship. Dyadic-level charting provided a systematic examination of individual and dyadic experiences. These findings indicate that access to informational and support services for dyads as they prepare to start dialysis may minimize negative effects on their relationship. [ABSTRACT FROM AUTHOR]

90% of the UK diabetic population are classified as T2DM. This study aims to compare outcomes after SPK transplant between recipients with T1DM or T2DM. Data on all UK SPK transplants from 2003-2019 were obtained from the NHSBT Registry ( n = 2,236). Current SPK transplant selection criteria for T2DM requires insulin treatment and recipient BMI < 30 kg/m 2 . After exclusions (re-transplants/ambiguous type of diabetes) we had a cohort of n = 2,154. Graft (GS) and patient (PS) survival analyses were conducted using Kaplan-Meier plots and Cox-regression models. Complications were compared using chi-squared analyses. 95.6% of SPK transplants were performed in recipients with T1DM ( n = 2,060). Univariate analysis showed comparable outcomes for pancreas GS at 1 year ( p = 0.120), 3 years ( p = 0.237), and 10 years ( p = 0.196) and kidney GS at 1 year ( p = 0.438), 3 years ( p = 0.548), and 10 years ( p = 0.947). PS was comparable at 1 year ( p = 0.886) and 3 years ( p = 0.237) and at 10 years ( p = 0.161). Multi-variate analysis showed comparable outcomes in pancreas GS ( p = 0.564, HR 1.221, 95% CI 0.619, 2.406) and PS( p = 0.556, HR 1.280, 95% CI 0.563, 2.911). Comparable rates of common complications were demonstrated. This is the largest series outside of the US evaluating outcomes after SPK transplants and shows similar outcomes between T1DM and T2DM recipients. It is hoped dissemination of this data will lead to increased referral rates and assessment of T2DM patients who could benefit from SPK transplantation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Owen, Carr, Counter, Tingle, Thompson, Manas, Shaw, Wilson and White.)

Background: Remote digital health interventions to enhance physical activity provide a potential solution to improve the sedentary behaviour, physical inactivity, and poor health-related quality of life that are typical of chronic conditions, particularly for people with chronic kidney disease. However, there is a need for high-quality evidence to support implementation in clinical practice. The Kidney BEAM trial evaluated the clinical effect of a 12-week physical activity digital health intervention on health-related quality of life., Methods: In a single-blind, randomised controlled trial conducted at 11 centres in the UK, adult participants (aged ≥18 years) with chronic kidney disease were recruited and randomly assigned (1:1) to the Kidney BEAM physical activity digital health intervention or a waiting list control group. Randomisation was performed with a web-based system, in randomly permuted blocks of six. Outcome assessors were masked to treatment allocation. The primary outcome was the difference in the Kidney Disease Quality of Life Short Form version 1.3 Mental Component Summary (KDQoL-SF1.3 MCS) between baseline and 12 weeks. The trial was powered to detect a clinically meaningful difference of 3 arbitrary units (AU) in KDQoL-SF1.3 MCS. Outcomes were analysed by an intention-to-treat approach using an analysis of covariance model, with baseline measures and age as covariates. The trial was registered with ClinicalTrials.gov, NCT04872933., Findings: Between May 6, 2021, and Oct 30, 2022, 1102 individuals were assessed for eligibility, of whom 340 participants were enrolled and randomly assigned to the Kidney BEAM intervention group (n=173) or the waiting list control group (n=167). 268 participants completed the trial (112 in the Kidney BEAM group and 156 in the waiting list control group). All 340 randomly assigned participants were included in the intention-to treat population. At 12 weeks, there was a significant improvement in KDQoL-SF.13 MCS score in the Kidney BEAM group (from mean 44·6 AU [SD 10·8] at baseline to 47·0 AU [10·6] at 12 weeks) compared with the waiting list control group (from 46·1 AU [10·5] to 45·0 AU [10·1]; between-group difference of 3·1 AU [95% CI 1·8-4·4]; p<0·0001)., Interpretation: The Kidney BEAM physical activity platform is an efficacious digital health intervention to improve mental health-related quality of life in patients with chronic kidney disease. These findings could facilitate the incorporation of remote digital health interventions into clinical practice and offer a potential intervention worthy of investigation in other chronic conditions., Funding: Kidney Research UK., Competing Interests: Declaration of interests King's College Hospital NHS Trust and SAG were involved in the conception and development of Kidney BEAM. SB is a trustee of Kidney Research UK. DCW has an ongoing consultancy contract with AstraZeneca and has received honoraria or consultancy fees from Astellas, Boehringer Ingelheim, Bayer, Eledon, Galderma, GlaxoSmithKline, Gilead, Janssen, Mundipharma, ProKidney, Tricida, Vifor, and Zydus for activities related to education and clinical trials. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the association between kidney function with the risk of dementia and brain volumes., Methods: A total of 452,996 UK Biobank participants with calculated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) were included. We utilized Cox proportional hazards regression models and restricted cubic spline analyses to examine the relationships between kidney function and the risk of all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VD). Additionally, we explored the correlations between kidney function and brain magnetic resonance indicators among 40,380 participants., Results: During a median follow-up of 12 years, 5,258 incident ACD cases were identified. The deterioration of kidney function was associated with an increased risk of ACD. When compared to eGFR ≥ 90 ml/min/1.73 m², the highest risk increase was evident for eGFRcre < 30 ml/min/1.73 m² (adjusted HR = 2.372, 95% CI: 1.444-3.897, P < 0.001), with eGFRcys showing greater significance (adjusted HR = 3.045, 95% CI: 2.212-4.191, P < 0.001), especially in relation to AD. Compared to the ACR level in the range of 3-30 mg/mmol, the category of > 30 mg/mmol was associated with an increased risk of ACD (adjusted HR = 1.720, 95% CI: 1.350-2.190, P < 0.001). Moreover, the decline in kidney function was associated with the total brain volume atrophy and reduction in certain subcortical areas., Conclusions: Our study indicates that diminished kidney function, as evidenced by a drop in eGFR and aggravated proteinuria, elevates dementia risk. Associated brain structural changes further underpin this connection from a neuro-pathophysiological perspective., Competing Interests: Declaration of Competing Interest The authors report that they have no competing interests relevant to the manuscript., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice., Methods: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes., Results: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff., Conclusion: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions., (© 2023. The Author(s).)

Summary: This review reports the outcomes of paediatric renal transplantation in the United Kingdom over the last 25 years. UK Transplant Registry data on 3236 paediatric renal transplants performed between 1 January 1992 and 31 December 2016 were analysed. Significant improvements in human leucocyte antigen (HLA) matching have been achieved; 84% of recipients received 000 or favourable (0 DR and 0 or 1 B) mismatched kidneys in 2016 compared with 27% in 1992. The median waiting time has increased from 126 days in 1999 to 351 days in 2016. Tacrolimus replaced ciclosporin in most immunosuppressive regimens after 2002. Renal transplant outcome has improved significantly, mainly because of a reduction in early graft loss. One‐year donation after brain death renal allograft survival for those transplanted from 2012 to 2016 was 98%, compared with 72% for those transplanted from 1987 to 1991. Renal allograft survival for first kidney only transplants at 1, 5, 10, 20 and 25 years were 89%, 79%, 65%, 42% and 33% respectively. Superior survival with living donor was maintained throughout the study period with 25‐year graft survival at 33% compared with 31% from deceased donor (P < 0.0001). Changes in immunosuppression regimens, improvements in HLA matching and a reduction of cold ischaemia time may in part explain the improvements in graft survival. [ABSTRACT FROM AUTHOR]

Large placebo-controlled trials have demonstrated kidney and cardiovascular clinical benefits of SGLT-2 inhibitors. Data from the EMPA-KIDNEY and DELIVER trials and associated meta-analyses triggered an update to the UK Kidney Association Clinical Practice Guideline on Sodium-Glucose Co-transporter-2 (SGLT-2) Inhibition in Adults with Kidney Disease. We provide a summary of the full guideline and highlight the rationale for recent updates. The use of SGLT-2 inhibitors in people with specific medical conditions, including type 1 diabetes, kidney transplants, and people admitted to hospital with heart failure is also considered, along with Recommendations for future research and Recommendations for implementation. A full "lay" summary of the guidelines is provided as an appendix to ensure that these guidelines are accessible and understandable to people who are not medical professionals., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Survival outcomes for kidney transplant candidates based on expanded criteria donor (ECD) kidney type is unknown. A retrospective cohort study was undertaken of prospectively collected registry data of all waitlisted kidney failure patients receiving dialysis in the United Kingdom. All patients listed for their first kidney-alone transplant between 2000-2019 were included. Treatment types included; living donor; standard criteria donor (SCD); ECD 60 (deceased donor aged ≥60 years); ECD 50-59 (deceased donor aged 50-59 years with two from the following three; hypertension; raised creatinine and/or death from stroke) or remains on dialysis. The primary outcome was all-cause mortality, with time-to-death from listing analyzed using time-dependent non-proportional Cox regression models. The study cohort comprised 47,917 waitlisted kidney failure patients, of whom 34,558 (72.1%) received kidney transplantation. ECD kidneys ( n = 7,356) were stratified as ECD 60 ( n = 7,009) or ECD 50-59 ( n = 347). Compared to SCD, both ECD 60 (Hazard Ratio 1.126, 95% CI 1.093-1.161) and ECD 50-59 (Hazard Ratio 1.228, 95% CI 1.113-1.356) kidney recipients have higher all-cause mortality. However, compared to dialysis, both ECD 60 (Hazard Ratio 0.194, 95% CI 0.187-0.201) and ECD 50-59 (Hazard Ratio 0.218, 95% CI 0.197-0.241) kidney recipients have lower all-cause mortality. ECD kidneys, regardless of definition, provide equivalent and superior survival benefits in comparison to remaining waitlisted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Patel, Brotherton, Chaudhry, Evison, Nieto, Dabare and Sharif.)

Background: Primary hyperoxaluria (PH) is a rare, genetic disorder which involves the overproduction of endogenous oxalate, leading to hyperoxaluria, recurrent urolithiasis and/or progressive nephrocalcinosis and eventually resulting in kidney failure and systemic oxalosis. The aim of this trial was to investigate whether treatment involving an oxalate-metabolising bacterium ( Oxalobacter formigenes) could reduce urinary oxalate excretion in PH patients. Methods: The efficacy and safety of O. formigenes (Oxabact® OC5; OxThera AB, Stockholm, Sweden) was evaluated in a randomised, placebo-controlled, double-blind study for 8 weeks. The primary objective was reduction in urinary oxalate excretion (Uox). Secondary objectives included faecal O. formigenes count and decrease in plasma oxalate concentration (Pox). Results: Twenty-eight patients randomised 1:1 to the treatment group (OC5) or the placebo group completed the study. After 8 weeks of treatment, there was no significant difference in the change in Uox (mmol/24 h/1.73 m) between the groups (OC5: +0.042, placebo: −0.140). Post-hoc analysis showed a statistically significant increase in Uox per urinary creatinine excretion in the OC5 group (OC5: +5.41, placebo: −15.96; p = 0.030). Change in Pox from baseline was not significantly different between groups ( p = 0.438). The O. formigenes cell count was significantly increased in OC5-treated patients ( p < 0.001) versus placebo. The treatment response to O. formigenes was related to individual stage of kidney deterioration, and Pox was directly correlated to kidney function, even for early-stage patients (chronic kidney disease stage 1). No safety issues were observed. Conclusions: Treatment with OC5 did not significantly reduce Uox or Pox over 8 weeks of treatment. The treatment was well tolerated and successfully delivered to the gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Background: Associations between kidney function and dementia risk are inconclusive. Chronic kidney disease (CKD) severity is determined by levels of both estimated glomerular filtration rate (eGFR) and the urine albumin to creatinine ratio (ACR). However, whether there is a graded increase in dementia risk for worse eGFR in each ACR category is unclear. Also, whether genetic risk for dementia impacts the associations is unknown. The current study aims to investigate the associations between eGFR and albuminuria with dementia risk both individually and jointly, whether the associations vary by different follow-up periods, and whether genetic factors modified the associations., Methods: In 202,702 participants aged ≥ 60 years from the UK Biobank, Cox proportional-hazards models were used to examine the associations between eGFR and urine albumin creatinine ratio (ACR) with risk of incident dementia. GFR was estimated based on serum creatinine, cystatin C, or both. The models were restricted to different follow-up periods (< 5 years, 5-10 years, and ≥ 10 years) to investigate potential reverse causation., Results: Over 15 years of follow-up, 6,042 participants developed dementia. Decreased kidney function (eGFR < 60 ml/min/1.73m 2 ) was associated with an increased risk of dementia (Hazard Ratio [HR] = 1.42, 95% Confidence Interval [CI] 1.28-1.58), compared to normal kidney function (≥ 90 ml/min/1.73m 2 ). The strength of the association remained consistent when the models were restricted to different periods of follow-up. The HRs for incident dementia were 1.16 (95% CI 1.07-1.26) and 2.24 (95% CI 1.79-2.80) for moderate (3-30 mg/mmol) and severely increased ACR (≥ 30 mg/mmol) compared to normal ACR (< 3 mg/mmol). Dose-response associations were observed when combining eGFR and ACR, with those in the severest eGFR and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34-9.43). APOE status significantly modified the association (p = 0.04), with stronger associations observed among participants with a lower genetic risk of dementia. There was no evidence of an interaction between kidney function and non-APOE polygenic risk of dementia with dementia risk (p = 0.42)., Conclusions: Kidney dysfunction and albuminuria were individually and jointly associated with higher dementia risk. The associations were greater amongst participants with a lower genetic risk of dementia based on APOE, but not non-APOE polygenic risk., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Despite improved patient and clinical outcomes, living donor kidney transplantation is underutilized in the United Kingdom, particularly among minority ethnic groups, compared to deceased donor kidney transplantation. This may in part be due to the way in which kidney services present information about treatment options. With a focus on ethnicity, semi structured interviews captured the views of 19 kidney healthcare professionals from two renal centres in West Yorkshire, about the decisional needs and context within which people with advanced kidney disease make transplant decisions. Data were analysed using thematic analysis. Themes were categorized into three groups: 1) Kidney healthcare professionals: language, cultural awareness, trusted personnel, and staff diversity, 2) Patient information resources: timing and setting of education and suitability of patient-facing information and, 3) People with advanced kidney disease: knowledge, risk perception, and cultural/religious beliefs. To our knowledge, this is the first study in the United Kingdom to investigate in depth, healthcare professionals' views on living donor kidney transplantation decision making. Six recommendations for service improvement/delivery to support decision making around living donor kidney transplantation among minority ethnic groups are described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ahmed, Winterbottom, Ahmed, Stoves and Daga.)

Background: Fabry disease is a rare, X-linked inherited lysosomal storage disorder, that manifests as a heterogeneous disease with renal, cardiac and nervous system involvement. The most common pain experienced by people with Fabry disease are episodes of neuropathic pain reported in up to 80% of classical hemizygous male patients and up to 65% of heterozygous female patients. No clear consensus exists within UK clinical practice for the assessment and management of pain in Fabry disease based on agreed clinical practice and clinical experience. Here we describe a modified Delphi initiative to establish expert consensus on management of pain in Fabry disease in the UK clinical setting., Methods: Delphi panel members were identified based on their demonstrated expertise in managing adult or paediatric patients with Fabry disease in the UK and recruited by an independent third-party administrator. Ten expert panellists agreed to participate in two survey rounds, during which they remained anonymous to each other. Circulation of the questionnaires, and collection and processing of the panel's responses were conducted between September 2021 and December 2021. All questions required an answer., Results: The Delphi panel reached a consensus on 21 out of 41 aspects of pain assessment and management of pain in Fabry disease. These encompassed steps in the care pathway from the goals of therapy through to holistic support, including the use of gabapentin and carbamazepine as first-line analgesic medications for the treatment of neuropathic pain in Fabry disease, as well as the proactive management of symptoms of anxiety and/or depression associated with Fabry pain., Conclusions: The consensus panel outcomes reported here have highlighted strengths in current UK clinical practice, along with unmet needs for further research and agreement. This consensus is intended to prompt the next steps towards developing clinical guidelines., (© 2023. The Author(s).)

Unspecified kidney donation (UKD) has made substantial contributions to the UK living donor programme. Nevertheless, some transplant professionals are uncomfortable with these individuals undergoing surgery. This study aimed to qualitatively explore the attitudes of UK healthcare professionals towards UKD. An opportunistic sample was recruited through the Barriers and Outcomes in Unspecified Donation (BOUnD) study covering six UK transplant centres: three high volume and three low volume centres. Interview transcripts were analysed using inductive thematic analysis. The study provided comprehensive coverage of the UK transplant community, involving 59 transplant professionals. We identified five themes: staff's conception of the ethics of UKD; presence of the known recipient in the donor-recipient dyad; need for better management of patient expectations; managing visceral reactions about the "typical" unspecified kidney donor; complex attitudes toward a promising new practice. This is the first in-depth qualitative study of attitudes of transplant professionals towards UKD. The data uncovered findings with strong clinical implications for the UKD programme, including the need for a uniform approach towards younger candidates that is adhered to by all transplant centres, the need to equally extend the rigorous assessment to both specified and unspecified donors, and a new approach to managing donor expectations., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zuchowski, Mamode, Draper, Gogalniceanu, Norton, Chilcot, Auburn, Clarke, Williams, Burnapp, McCrone and Maple.)

Background: Deceased donor kidneys are often declined for ≥1 patients but then implanted into another. Studies are needed to guide transplant clinicians and patients, especially given the increasing age and comorbidity of donors. This study compares outcomes of recipients of transplanted kidneys that were initially declined with outcomes of patients who remained on the waiting list., Methods: This UK Transplant Registry study examined named-patient, adult donation after brain death donor single kidney-only offers that were declined for donor- or organ-related reasons (DORRs), in which the kidney was subsequently transplanted from January 1, 2010, to December 31, 2018. Outcomes included graft function and survival of kidneys transplanted following DORR decline, survival and transplant status of patients who had a kidney declined, and intercenter decline rates., Results: A total of 4722 kidneys declined for DORRs, which eventually resulted in single kidney-only transplants, were examined. One year after the offer decline, 35% of patients for whom the organ was declined remained on the list, 55% received a deceased donor transplant at a median of 174 d after the initial offer decline, and 4% had been removed or died. For patients transplanted following offer decline, there was no significant difference in 5-y graft survival when comparing the outcomes to those recipients who received the declined kidney. There was significant variation in DORR decline rates between UK transplant units (17%-54%)., Conclusions: This study shows reasonable outcomes of kidneys previously declined for DORRs and supports the utilization of those considered to be of higher risk for carefully selected recipients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Vascular complications in kidney transplant surgery constitute one-third of early graft loss, which can be prevented by timely diagnosis of vascular compromise. A blood flow monitoring device may have a beneficial role in the early identification of graft hypoperfusion critical to reducing graft loss. This research protocol aims to evaluate the potential of an implantable Doppler probe as a blood flow monitoring device in kidney transplant recipients., Materials and Methods: The potential study will be a mixed methodology, 2-arm feasibility randomized controlled trial with an embedded qualitative study. For the trial, we will compare demographic characteristics and outcome measures of kidney transplant patients receiving implantable Doppler probe monitoring (intervention group, n = 30) with those having standard clinical care (control group). For the qualitative study, we will conduct semi-structured interviews with stakeholders (n = 12) recruited by purposive sampling to explore experiences of participants. All interviews will be audio recorded with verbatim transcription., Results: Our results will use the summarized quantitative data and descriptive statistics to determine differences between the groups. We will use CONSORT guidelines to determine the suitability of the research processes, availability of research resources, and potential challenges faced during the feasibility randomized controlled trial. We will use thematic analysis and NVivo software to analyze the acceptability of the intervention in clinical practice. We will compile the results according to the consolidated criteria for reporting qualitative research checklist., Conclusions: The goal of this protocol is to determine the feasibility of an implantable Doppler probe monitoring device in kidney transplant recipients. The feasibility study will collect preliminary information, fill gaps in evidence, and test research processes for the pragmatic future randomized controlled trial. The template of this study is transferable to other transplant centers across the United Kingdom.

In the absence of population-based screening, addition of screening for kidney cancer to lung cancer screening could provide an efficient and low-resource means to improve early detection. In this study, we used the UK Biobank cohort (n = 442 865) to determine the performance of the Yorkshire Lung Cancer Screening Trial (YLST) eligibility criteria for selecting individuals for kidney cancer screening. We measured the performance of two models widely used to determine eligibility for lung cancer screening (PLCO[m2012] and the Liverpool-Lung-Project-v2) and the performance of the combined YLST criteria. We found that the lung cancer models have discrimination (area under the receiver operating curve) between 0.60 and 0.68 for kidney cancer. In the UK, one in four cases (25%) of kidney cancer cases is expected to occur in those eligible for lung cancer screening, and one case of kidney cancer detected for every 200 people invited to lung cancer screening. These results suggest that adding kidney cancer screening to lung cancer screening would be an effective strategy to improve early detection rates of kidney cancer. However, most kidney cancers would not be picked up by this approach. This analysis does not address other important considerations about kidney cancer screening, such as overdiagnosis. PATIENT SUMMARY: It has been proposed that adding-on kidney cancer screening to lung cancer screening (both carried out by a computed tomography scan of the chest/abdomen) would be an easy and low-cost way of detecting cases of kidney cancer earlier, when these can be treated more easily. Lung cancer screening is usually targeted at people who are at a high risk (eg, older smokers); therefore, here we look at whether the same group of people are also at a high risk of kidney cancer. Our analysis shows that one in four people later diagnosed with kidney cancer are also at a high risk of lung cancer; hence, a combined screening programme could detect up to a quarter of kidney cancers., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

In this article, Laura Pankhurst et al report key figures about kidney transplantation in the UK, including information on the transplant list, transplant activity and survival after kidney transplant for all 24 centres performing kidney transplantation. Data were obtained from the UK Transplant Registry on kidney transplant activity between April 2008 and March 2018 [ABSTRACT FROM AUTHOR]

Genome-wide association studies have discovered hundreds of associations between common genotypes and kidney function but cannot comprehensively investigate rare coding variants. Here, we apply a genotype imputation approach to whole exome sequencing data from the UK Biobank to increase sample size from 166,891 to 408,511. We detect 158 rare variants and 105 genes significantly associated with one or more of five kidney function traits, including genes not previously linked to kidney disease in humans. The imputation-powered findings derive support from clinical record-based kidney disease information, such as for a previously unreported splice allele in PKD2, and from functional studies of a previously unreported frameshift allele in CLDN10. This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource ( https://ckdgen-ukbb.gm.eurac.edu/ ) to direct experimental and clinical studies of kidney disease., (© 2023. The Author(s).)

Background: Few evidence-based, on-line resources exist to support home-based care of childhood long-term conditions.Methods: In a feasibility study, children with stages 3, 4, or 5 chronic kidney disease, parents and professionals collaboratively developed a novel Online Parent Information and Support (OPIS) application. Parents were randomized to an intervention arm with access to OPIS or a control arm without access. OPIS usage was assessed using Google Analytics. Parents in the intervention arm completed the Suitability Assessment of Materials (SAM) and User Interface Satisfaction (USE) questionnaires and participated in qualitative interviews.Results: Twenty parents accessed OPIS with a mean of 23.3 (SD 20.8, range 2-64) visits per user. Responses from the SAM and USE questionnaires were positive, most respondents rating OPIS highly and finding it easy to use. Qualitative suggestions include refinement of OPIS components, enabling personalization of OPIS functionalities and proactive endorsements of OPIS by professionals.Conclusions: Implementation of OPIS into standard practice is feasible in the centre where it was developed. Suggested developments will augment reported strengths to inform ongoing testing in the wider UK network of units. Our design and methods are transferrable to developing and evaluating web-applications to support home-based clinical care-giving for other long-term conditions. [ABSTRACT FROM AUTHOR]

Background South Asian individuals have increased cardiovascular disease and mortality risks. Reliance on creatinine- rather than cystatin C-based estimated glomerular filtration rate (eGFRcys) may underestimate the cardiovascular disease risk associated with chronic kidney disease. Methods and Results Among 7738 South Asian UK BioBank participants without prevalent heart failure (HF) or atherosclerotic cardiovascular disease, we investigated associations of 4 eGFRcys and creatinine-based estimated glomerular filtration rate categories (<45, 45-59, 60-89, and ≥90 mL/min per 1.73 m 2 ) with risks of all-cause mortality, incident HF, and incident atherosclerotic cardiovascular disease. The mean age was 53±8 years; 4085 (53%) were women. Compared with creatinine, cystatin C identified triple the number of participants with estimated glomerular filtration <45 (n=35 versus n=113) and 6 times the number with estimated glomerular filtration 45 to 59 (n=80 versus n=481). After multivariable adjustment, the eGFRcys 45 to 59 category was associated with higher risks of mortality (hazard ratio [HR], 2.38 [95% CI, 1.55-3.65]) and incident HF (sub-HR [sHR], 1.87 [95% CI, 1.09-3.22]) versus the eGFRcys ≥90 category; the creatinine-based estimated glomerular filtration rate 45 to 59 category had no significant associations with outcomes. Of the 7623 participants with creatinine-based estimated glomerular filtration rate ≥60, 498 (6.5%) were reclassified into eGFRcys <60 categories. Participants who were reclassified as having eGFRcys <45 had higher risks of mortality (HR, 4.88 [95% CI, 2.56-9.31]), incident HF (sHR, 4.96 [95% CI, 2.21-11.16]), and incident atherosclerotic cardiovascular disease (sHR, 2.29 [95% CI, 1.14-4.61]) versus those with eGFRcys ≥90; those reclassified as having eGFRcys 45 to 59 had double the mortality risk (HR, 2.25 [95% CI, 1.45-3.51]). Conclusions Among South Asian individuals, cystatin C identified a high-risk chronic kidney disease population that was not detected by creatinine and enhanced estimated glomerular filtration rate-based risk stratification for mortality, incident HF, and incident atherosclerotic cardiovascular disease.

Aims: To describe the aetiologies of paediatric rhabdomyolysis and explore the medium-term renal consequences., Methods: Retrospective, single-centre review of children with rhabdomyolysis., Results: Two hundred and thirty-two children met inclusion criteria for the analysis. Mean age at presentation was 8.4 (SD ± 5.5) years. The commonest aetiology was infection (28%), with viral myositis making up the clear majority (75%). Trauma was identified as a cause in 18% of children, seizures in 10% and immune-mediated mechanisms in 8%. Acute kidney injury (AKI) was present in 32% of the cases overall. Children with AKI tended to be younger, with higher peak creatine kinase (CK) and active urinary sediment on urinalysis at presentation. AKI and the need for renal replacement therapy (RRT) were associated with a prolonged hospital stay (15 (interquartile range, IQR 6.5-33) vs. 2 (IQR 0-7) days). A total of 18 children and young people required RRT, with a mean duration of 7.1 ± 4.3 days. Those who received RRT were more likely to have abnormalities on urinalysis at presentation (46% vs. 5%). Over the period of the study, 9% of children died and 2% met criteria for a diagnosis of chronic kidney disease., Conclusions: This large paediatric rhabdomyolysis case series provides new and unique insights into the condition. Our results highlight the common aetiologies and provide evidence of good renal recovery overall, even in the most severely affected cases. Abnormalities of urinalysis appear to be important in predicting the development of AKI and the need for RRT., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Introduction A 'new' fast track kidney allocation scheme ( FTKAS) was implemented in the UK in 2012 for offering of previously declined kidneys. We evaluated the impact of the FTKAS in utilization of declined kidneys and outcome. Methods Adult renal transplant centers were surveyed. Overall utilization was evaluated using National Health Service Blood and Transplant ( NHSBT) data. Outcome of FTKAS kidneys in our center was analyzed. Results Centers cited graft, patient outcome concerns, and inadequate logistical support for their non- FTKAS participation. In the first year of the scheme, 266 kidneys were offered through the FTKAS, 158 were transplanted in 10 centers (59%). In comparison, 166 kidneys were offered through previous system over five yr (2006-2011), and 65 were utilized in 59 transplants (39%). In our center, 42 kidneys were transplanted in 39 recipients. One-yr graft and patient survival were both 95%. Results were comparable to a matched group of kidney transplants during the same periods allocated via the standard scheme. Conclusions The FTKAS has led to effective utilization of the declined kidneys with outcome comparable to kidneys allocated through the standard scheme. Non-participation based on outcome concerns is mostly subjective while logistical issues need to be addressed. [ABSTRACT FROM AUTHOR]

Summary: Ethnic differences in renal calcium and phosphate excretion exist, which may depend on differences in their dietary intakes and regulatory factors. We report highly significant differences in urinary calcium and phosphate excretion between white British and Gambian adults after statistical adjustment for mineral intakes, indicating an independent effect of ethnicity. Introduction: Populations vary in their risk of age-related osteoporosis. There are racial or ethnic differences in the metabolism of the bone-forming minerals calcium (Ca) and phosphate (P), with a lower renal Ca and P excretion in African-Americans compared to white counterparts, even at similar intakes and rates of absorption. Also, Africans in The Gambia have a lower Ca excretion compared to white British subjects, groups known to differ in their dietary Ca intake. Here, we report on differences in urinary Ca and P excretion between Gambian and white British adults while allowing for known predictors, including dietary intakes. Methods: Participants were healthy white British ( n = 60) and Gambian ( n = 61) men and women aged 60-75 years. Fasting blood and 2-h urine samples were collected. Markers of Ca and P metabolism were analysed. Dietary intake was assessed with country-specific methods. Results: White British older adults had higher creatinine-corrected urinary Ca and P excretion (uCa/uCr, uP/uCr) and lower tubular maximum of Ca and P compared to Gambian counterparts. The predictors of urinary Ca and P differed between groups. Multiple regression analysis showed that dietary Ca and Ca/P were predictors of uCa/uCr and uP/uCr, respectively. Ethnicity remained a significant predictor of uCa/uCr and uP/uCr after adjustment for diet and other factors. Conclusions: Gambian older adults have higher renal Ca conservation than British counterparts. Dietary mineral intakes were predictors of the differences in urinary Ca and P excretion, but ethnicity remained a highly significant predictor after statistical adjustment. This suggests that ethnicity has an independent effect on renal Ca and P handling. [ABSTRACT FROM AUTHOR]

Background: the oldest old (85+) pose complex medical challenges. Both underdiagnosis and overdiagnosis are claimed in this group.Objective: to estimate diagnosis, prescribing and hospital admission prevalence from 2003/4 to 2011/12, to monitor trends in medicalisation.Design and setting: observational study of Clinical Practice Research Datalink (CPRD) electronic medical records from general practice populations (eligible; n = 27,109) with oversampling of the oldest old.Methods: we identified 18 common diseases and five geriatric syndromes (dizziness, incontinence, skin ulcers, falls and fractures) from Read codes. We counted medications prescribed ≥1 time in all quarters of studied years.Results: there were major increases in recorded prevalence of most conditions in the 85+ group, especially chronic kidney disease (stages 3–5: prevalence <1% rising to 36.4%). The proportions of the 85+ group with ≥3 conditions rose from 32.2 to 55.1% (27.1 to 35.1% in the 65–84 year group). Geriatric syndrome trends were less marked. In the 85+ age group the proportion receiving no chronically prescribed medications fell from 29.6 to 13.6%, while the proportion on ≥3 rose from 44.6 to 66.2%. The proportion of 85+ year olds with ≥1 hospital admissions per year rose from 27.6 to 35.4%.Conclusions: there has been a dramatic increase in the medicalisation of the oldest old, evident in increased diagnosis (likely partly due to better record keeping) but also increased prescribing and hospitalisation. Diagnostic trends especially for chronic kidney disease may raise concerns about overdiagnosis. These findings provide new urgency to questions about the appropriateness of multiple diagnostic labelling. [ABSTRACT FROM PUBLISHER]

Background There is no national policy for allocation of kidneys from Donation after circulatory death (DCD) donors in the UK. Allocation is geographical and based on individual/regional centre policies. We have evaluated the short term outcomes of paired kidneys from DCD donors subject to this allocation policy. Methods Retrospective analysis of paired renal transplants from DCD's from 2002 to 2010 in London. Cold ischemia time (CIT), recipient risk factors, delayed graft function (DGF), 3 and 12 month creatinine) were compared. Results Complete data was available on 129 paired kidneys.115 pairs were transplanted in the same centre and 14 pairs transplanted in different centres. There was a significant increase in CIT in kidneys transplanted second when both kidneys were accepted by the same centre (15.5 ± 4.1 vs 20.5 ± 5.8 hrs p < 0.0001 and at different centres (15.8 ± 5.3 vs. 25.2 ± 5.5 hrs p = 0.0008). DGF rates were increased in the second implant following sequential transplantation (p = 0.05). Conclusions Paired study sequential transplantation of kidneys from DCD donors results in a significant increase in CIT for the second kidney, with an increased risk of DGF. Sequential transplantation from a DCD donor should be avoided either by the availability of resources to undertake simultaneous procedures or the allocation of kidneys to 2 separate centres. [ABSTRACT FROM AUTHOR]

End-stage kidney disease is a significant burden on the healthcare systems of many countries, and this is likely to continue because of an increasingly aging and comorbid population. Multiple studies have demonstrated a significant clinical benefit in transplantation when compared with dialysis, however, there continues to be a shortage of donor kidneys available. This article provides an economic perspective on issues pertinent to living kidney donation and transplantation. Although ethics, equity, and cultural considerations often seem at odds with economic concepts around resource allocation, this article explains the situation around supply and demand for living kidneys and illustrates how this has been addressed in the economic literature. The article discusses different policy recommendations for resolving the imbalance between supply and demand in kidney donation, through policies under 3 main approaches: increasing supply, decreasing demand, and improving the allocation of kidney supply., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Decreased renal function is a potential risk factor for dementia., Methods: This retrospective cohort study of 2.8 million adults aged ≥50 years used the IMRD-THIN database, representative of UK primary care, from January 1, 1995 to February 24, 2020. The associations between estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (ACR) with incident all-cause dementia were analyzed using Cox regression., Results: In the eGFR cohort (n = 2,797,384), worsening renal dysfunction was associated with increased hazard of all-cause dementia, with greatest hazard at eGFR 15-30 ml/min/1.73min 2 (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.19-1.33). In the ACR cohort (n = 641,912), the hazard of dementia increased from ACR 3-30 mg/mmol (HR 1.13, 95% CI 1.10-1.15) to ACR > 30 mg/mmol (HR 1.25, 95% CI 1.18-1.33)., Discussion: Worsening eGFR and albuminuria have graded associations with the risk of dementia, which may have significant implications for the care of patients with kidney disease., (© 2021 the Alzheimer's Association.)

Background: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation., Methods: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported., Results: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors., Conclusions: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases., (© 2022 Wiley Periodicals LLC.)

Beta-thalassaemia is characterised by progressive anaemia necessitating regular blood transfusions to sustain life. With the advent of effective chelating agents that can reduce the iron burden and extend patients' survival, renal disease, as in other ageing populations, has become more prevalent. In recent years, chronic kidney disease ( CKD) has become overwhelming; indeed, approximately 8% or 6 million people of the UK population has evidence of CKD. Several factors, which occur in patients with thalassaemia, account for the relative explosion of renal disease in the general population including increasing age, diabetes, hypertension and the advent of novel measures of renal function facilitating early detection of kidney disease. In addition, some patients with thalassaemia develop renal tubular dysfunction related to the disease itself, the effects of iron overload and the effects of chelator therapy, while other patients have an increased creatinine clearance leading to hyperfiltration. More recently, there is a noticeable increasing prevalence of impaired renal function and proteinuria because of several putative factors including chelators. We review current data on the potential mechanisms leading to renal abnormalities seen in patients with thalassaemia, the potential effects of iron loading within the kidney and the potential renal effects of chelator therapy. This article gives a speculative account of possible mechanisms and theories to consider providing pause for thought and direct future research in this area. [ABSTRACT FROM AUTHOR]

Objectives The aim of the study was to investigate the prevalence and aetiology of chronic kidney disease (CKD) and trends in estimated glomerular filtration rate (eGFR) in HIV-infected patients. Methods Ascertainment and review of CKD cases among patients attending King's College and Brighton Hospitals, UK were carried out. CKD was defined as eGFR <60 mL/min for ≥3 months. Longitudinal eGFR slopes were produced to examine trends in renal function before, during and after exposure to indinavir (IDV) or tenofovir (TFV). Results CKD prevalence was 2.4%. While HIV-associated nephropathy accounted for 62% of CKD in black patients, 95% of CKD in white/other patients was associated with diabetes mellitus, hypertension, atherosclerosis and/or drug toxicity. Exposure to IDV or TFV was associated with an accelerated decline in renal function (4.6-fold and 3.7-fold, respectively) in patients with CKD. In patients initiating IDV, age ≥50 years increased the odds of CKD [odds ratio (OR) 4.9], while in patients initiating TFV, age ≥50 years (OR 5.4) and eGFR 60–75 mL/min (OR 17.2) were associated with developing CKD. Conclusion This study highlights the importance of metabolic and vascular disease to the burden of CKD in an ageing HIV-infected cohort. In patients who developed CKD, treatment with IDV or TFV was associated with an accelerated decline in renal function. [ABSTRACT FROM AUTHOR]

Abstract: Approximately 2000 kidney transplants are performed every year in the UK. Owing to advances in surgical technique and immunosuppression therapy, transplantation is now the preferred method of renal replacement therapy for most patients with established renal failure (ERF). Donor organs have traditionally been harvested from deceased heart-beating donors but other forms of donation (e.g. non-heart-beating donors and living donors) are increasingly being utilized. Patients with ERF have complex multisystem disease and are a high-risk group for anaesthesia and surgery. Cardiovascular disease is common and is the main cause of mortality following transplantation. Major preoperative considerations include evaluation of cardiorespiratory function and assessment of fluid and electrolyte balance. The main perioperative aim is to optimize graft function. Strategies include careful fluid management aided by central venous monitoring, maintenance of a mean arterial pressure of 70–80 mm Hg and administration of corticosteroid and mannitol around the time of graft reperfusion. Postoperative care is on a specialist ward and managed by protocols addressing fluid, pain and immunosuppression management. Living-donor kidney transplants now account for approximately one-third of all kidney transplants. Following a thorough evaluation process the living donor undergoes a unilateral nephrectomy performed either laparoscopically or as an open procedure. [Copyright &y& Elsevier]

The prevalence of renal myxosporidiosis in wild brown trout, Salmo trutta, in seven river catchments in South-West England was investigated. Three hundred and twenty-seven fish were sampled from 16 sites, of which 54 (16.5%) were found, by histological examination of the kidney, to be infected with Tetracapsuloides bryosalmonae, the causative agent of proliferative kidney disease. No T. bryosalmonae infected fish were found in one river catchment, in other catchments the prevalence ranged from 2.5% to 36%. Hepatitis was strongly associated with the presence of T. bryosalmonae (odds ratio = 20.2, P < 0.001). Chloromyxum schurovi was found in 25% of fish and in six of seven river catchments, where the prevalence ranged from 2.4% to 63%. There was a strong negative association between the presence of T. bryosalmonae and C. schurovi (odds ratio = 0.10, P < 0.001). A hierarchical binomal model of the variance indicated that for T. bryosalmonae most of the variance existed at the site level, whereas for C. schurovi most variance existed at the river catchment level, suggesting that prevalence of T. bryosalmonae infection is determined largely by site level factors (e.g. presence of alternate host). The intraclass correlation coefficients (ICC) were 0.2 and 0.4 for T. bryosalmonae and C. schurovi, respectively, indicating the latter has higher effective transmission because of a higher level of infectiousness and/or abundance of alternate oligochaete hosts. These values can be used in future studies to estimate the sample sizes required to generate prevalence estimates with the required precision. [ABSTRACT FROM AUTHOR]