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Key words: continuous ambulatory peritoneal dialysis; Crohn's disease; fluid replacement; rehydration; short-bowel syndrome [ABSTRACT FROM PUBLISHER]

Background: Acute kidney injury commonly occurs in patients admitted to ICU. After acute kidney injury, kidney function may not completely recover leading to increased risk of future cardiovascular events. We sought to ascertain the rates of cardiovascular events in ICU survivors and if these rates were affected by the presence of acute kidney injury whilst in ICU., Methods: This retrospective observational cohort study utilised routinely collected data to identify patients who had survived an admission to one of two ICUs between July 2015 and June 2018. Baseline serum creatinine and subsequent values were used to identify acute kidney injury. Major adverse cardiovascular events described were myocardial injury, coronary artery intervention, or radiological evidence of stroke., Results: Of the 3994 ICU survivors, major adverse cardiovascular events were identified in 385 patients (9.6%; 95% confidence interval [CI] 8.8-10.6%). Presence of acute kidney injury whilst in ICU was significantly associated with future major adverse cardiovascular events (hazard ratio=1.38; 95% CI 1.12-1.70; P -value=0.003) and future biochemical myocardial injury (hazard ratio=1.48; 95% CI 1.16-1.89; P -value=0.001). Acute kidney injury did not have a statistically significant association with future coronary artery interventions or future cerebrovascular events., Conclusions: One in 10 ICU survivors experiences a major adverse cardiovascular event after discharge. Acute kidney injury whilst in ICU was associated with an increased risk of major adverse cardiovascular events and specifically myocardial injury. Further research is warranted on whether ICU survivors with acute kidney injury merit enhanced strategies for cardiovascular protection., (© 2023 The Authors.)

Introduction: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) causes autoimmune-mediated inflammation of small blood vessels in multiple organs, including the kidneys. The ability to accurately predict kidney outcomes would enable a more personalized therapeutic approach., Methods: We used our national renal biopsy registry to validate the ability of ANCA Renal Risk Score (ARRS) to predict end-stage kidney disease (ESKD) for individual patients. This score uses histopathological and biochemical data to stratify patients as high, medium, or low risk for developing ESKD., Results: A total of 288 patients were eligible for inclusion in the study (low risk n  = 144, medium risk n  = 122, high risk n  = 12). Using adjusted Cox proportional hazard models with the low-risk group as reference, we show that outcome differs between the categories: high-risk hazard ratio (HR) 16.69 (2.91-95.81, P  = 0.002); medium risk HR 4.14 (1.07-16.01, P  = 0.039). Incremental multivariable-adjusted Cox proportional hazards models demonstrated that adding ARRS to a model adjusted for multiple clinical parameters enhanced predictive discrimination (basic model C-statistic 0.864 [95% CI 0.813-0.914], basic model plus ARRS C-statistic 0.877 [95% CI 0.823-0.931]; P  <0.01)., Conclusion: The ARRS better discriminates risk of ESKD in AAV and offers clinicians more prognostic information than the use of standard biochemical and clinical measures alone. This is the first time the ARRS has been validated in a national cohort. The proportion of patients with high-risk scores is lower in our cohort compared to others and should be noted as a limitation of this study., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Background: Physical frailty is a major health concern among people receiving haemodialysis (HD) for stage-5 chronic kidney disease (CKD-5). Wearable accelerometers are increasingly being recommended to objectively monitor activity levels in CKD-5 and recent research suggests they may also represent an innovative strategy to evaluate physical frailty in vulnerable populations. However, no study has yet explored whether wearable accelerometers may be utilised to assess frailty in the context of CKD-5-HD. Therefore, we aimed to examine the diagnostic performance of a research-grade wearable accelerometer in evaluating physical frailty in people receiving HD., Methods: Fifty-nine people receiving maintenance HD [age = 62.3 years (SD = 14.9), 40.7% female] participated in this cross-sectional study. Participants wore a uniaxial accelerometer (ActivPAL) for seven consecutive days and the following measures were recorded: total number of daily steps and sit-to-stand transitions, number of daily steps walked with cadence < 60 steps/min, 60-79 steps/min, 80-99 steps/min, 100-119 steps/min, and ≥ 120 steps/min. The Fried phenotype was used to evaluate physical frailty. Receiver operating characteristics (ROC) analyses were performed to examine the diagnostic accuracy of the accelerometer-derived measures in detecting physical frailty status., Results: Participants classified as frail (n = 22, 37.3%) had a lower number of daily steps (2363 ± 1525 vs 3585 ± 1765, p = 0.009), daily sit-to-stand transitions (31.8 ± 10.3 vs 40.6 ± 12.1, p = 0.006), and lower number of steps walked with cadence of 100-119 steps/min (336 ± 486 vs 983 ± 797, p < 0.001) compared to their non-frail counterparts. In ROC analysis, the number of daily steps walked with cadence ≥ 100 steps/min exhibited the highest diagnostic performance (AUC = 0.80, 95% CI: 0.68-0.92, p < 0.001, cut-off ≤ 288 steps, sensitivity = 73%, specificity = 76%, PPV = 0.64, NPV = 0.82, accuracy = 75%) in detecting physical frailty., Conclusions: This study provided initial evidence that a wearable accelerometer may be a useful tool in evaluating physical frailty in people receiving HD. While the total number of daily steps and sit-to-stand transitions could significantly discriminate frailty status, the number of daily steps walked with cadences reflecting moderate to vigorous intensity of walking may be more useful in monitoring physical frailty in people receiving HD., (© 2023. The Author(s).)

Significance Statement: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict 2- and 5-year risk of kidney failure in populations with eGFR <60 ml/min per 1.73 m 2 . However, the CKD-EPI 2021 creatinine equation for eGFR is now recommended for use but has not been fully tested in the context of KFRE. In 59 cohorts comprising 312,424 patients with CKD, the authors assessed the predictive performance and calibration associated with the use of the CKD-EPI 2021 equation and whether additional variables and accounting for the competing risk of death improves the KFRE's performance. The KFRE generally performed well using the CKD-EPI 2021 eGFR in populations with eGFR <45 ml/min per 1.73 m 2 and was not improved by adding the 2-year prior eGFR slope and cardiovascular comorbidities., Background: The kidney failure risk equation (KFRE) uses age, sex, GFR, and urine albumin-to-creatinine ratio (ACR) to predict kidney failure risk in people with GFR <60 ml/min per 1.73 m 2 ., Methods: Using 59 cohorts with 312,424 patients with CKD, we tested several modifications to the KFRE for their potential to improve the KFRE: using the CKD-EPI 2021 creatinine equation for eGFR, substituting 1-year average ACR for single-measure ACR and 1-year average eGFR in participants with high eGFR variability, and adding 2-year prior eGFR slope and cardiovascular comorbidities. We also assessed calibration of the KFRE in subgroups of eGFR and age before and after accounting for the competing risk of death., Results: The KFRE remained accurate and well calibrated overall using the CKD-EPI 2021 eGFR equation. The other modifications did not improve KFRE performance. In subgroups of eGFR 45-59 ml/min per 1.73 m 2 and in older adults using the 5-year time horizon, the KFRE demonstrated systematic underprediction and overprediction, respectively. We developed and tested a new model with a spline term in eGFR and incorporating the competing risk of mortality, resulting in more accurate calibration in those specific subgroups but not overall., Conclusions: The original KFRE is generally accurate for eGFR <45 ml/min per 1.73 m 2 when using the CKD-EPI 2021 equation. Incorporating competing risk methodology and splines for eGFR may improve calibration in low-risk settings with longer time horizons. Including historical averages, eGFR slopes, or a competing risk design did not meaningfully alter KFRE performance in most circumstances., (Copyright © 2023 by the American Society of Nephrology.)

Objectives: To determine the incidence and characteristics of ICU admissions in the Scottish population of patients treated with chronic kidney replacement therapy (KRT) over an 11-year period and determine factors associated with post-ICU admission mortality., Design: Retrospective observational cohort study., Setting: We analyzed admissions to Scottish intensive care environments between January 1, 2009, and December 31, 2019., Patients: All patients receiving chronic KRT-including maintenance dialysis and kidney transplant-in Scotland., Intervention: None., Measurements and Main Results: Descriptive statistics and factors associated with mortality using logistic regression and Cox proportional hazard models. From 10,657 unique individuals registered in the Scottish Renal Registry over the 11-year study period and alive as of January 1, 2009, 1,402 adult patients were identified as being admitted to a Scottish critical care setting. Between 2009 and 2019, admissions to ICU increased in a nonlinear manner driven by increases in admissions for renal causes and elective cardiac surgery. The ICU admission rate was higher among patients on chronic dialysis than in kidney transplant recipients (59.1 vs 19.9 per 1,000 person-years), but post-ICU mortality was similar (about 24% at 30 d and 40% at 1 year). Admissions for renal reasons were most common (20.9%) in patients undergoing chronic dialysis, whereas kidney transplant recipients were most frequently admitted for pneumonia (19.3%) or sepsis (12.8%). Adjusted Cox PH models showed that receiving invasive ventilation and vasoactive drugs was associated with an increased risk of death at 30 days post-ICU admission (HR, 1.75; 95% CI, 1.28-2.39 and 1.72; 95% CI, 1.28-2.31, respectively)., Conclusions: With a growing population of kidney transplant recipients and the improved survival of patients on chronic dialysis, the number of ICU admissions is rising in the chronic KRT population. Mortality post-ICU admission is high for these patients., Competing Interests: Dr. Bell received funding from Astra Zeneca. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Lymphocyte ratios reflect inflammation and have been associated with adverse outcomes in a range of diseases. We sought to determine any association between neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) and mortality in a haemodialysis cohort, including a coronavirus disease 2019 (COVID-19) infection subpopulation., Methods: A retrospective analysis was performed of adults commencing hospital haemodialysis in the West of Scotland during 2010-21. NLR and PLR were calculated from routine samples around haemodialysis initiation. Kaplan-Meier and Cox proportional hazards analyses were used to assess mortality associations., Results: In 1720 haemodialysis patients over a median of 21.9 (interquartile range 9.1-42.9) months, there were 840 all-cause deaths. NLR but not PLR was associated with all-cause mortality after multivariable adjustment [adjusted hazard ratio (aHR) for in participants with baseline NLR in quartile 4 (NLR ≥8.23) versus quartile 1 (NLR <3.12) 1.63, 95% confidence interval (CI) 1.32-2.00]. The association was stronger for cardiovascular death (NLR quartile 4 versus 1 aHR 3.06, 95% CI 1.53-6.09) than for non-cardiovascular death (NLR quartile 4 versus 1 aHR 1.85, 95% CI 1.34-2.56). In the COVID-19 subpopulation, both NLR and PLR at haemodialysis initiation were associated with risk of COVID-19-related death after adjustment for age and sex (NLR: aHR 4.69, 95% CI 1.48-14.92 and PLR: aHR 3.40, 95% CI 1.02-11.36; for highest vs lowest quartiles)., Conclusions: NLR is strongly associated with mortality in haemodialysis patients while the association between PLR and adverse outcomes is weaker. NLR is an inexpensive, readily available biomarker with potential utility in risk stratification of haemodialysis patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Objective: To predict adverse kidney outcomes for use in optimizing medical management and clinical trial design., Research Design and Methods: In this meta-analysis of individual participant data, 43 cohorts (N = 1,621,817) from research studies, electronic medical records, and clinical trials with global representation were separated into development and validation cohorts. Models were developed and validated within strata of diabetes mellitus (presence or absence) and estimated glomerular filtration rate (eGFR; ≥60 or <60 mL/min/1.73 m2) to predict a composite of ≥40% decline in eGFR or kidney failure (i.e., receipt of kidney replacement therapy) over 2-3 years., Results: There were 17,399 and 24,591 events in development and validation cohorts, respectively. Models predicting ≥40% eGFR decline or kidney failure incorporated age, sex, eGFR, albuminuria, systolic blood pressure, antihypertensive medication use, history of heart failure, coronary heart disease, atrial fibrillation, smoking status, and BMI, and, in those with diabetes, hemoglobin A1c, insulin use, and oral diabetes medication use. The median C-statistic was 0.774 (interquartile range [IQR] = 0.753, 0.782) in the diabetes and higher-eGFR validation cohorts; 0.769 (IQR = 0.758, 0.808) in the diabetes and lower-eGFR validation cohorts; 0.740 (IQR = 0.717, 0.763) in the no diabetes and higher-eGFR validation cohorts; and 0.750 (IQR = 0.731, 0.785) in the no diabetes and lower-eGFR validation cohorts. Incorporating the previous 2-year eGFR slope minimally improved model performance, and then only in the higher-eGFR cohorts., Conclusions: Novel prediction equations for a decline of ≥40% in eGFR can be applied successfully for use in the general population in persons with and without diabetes with higher or lower eGFR., (© 2022 by the American Diabetes Association.)

Rationale & Objective: There is a dearth of data characterizing patients receiving kidney replacement therapy (KRT) for kidney failure due to systemic lupus erythematosus (SLE) and their clinical outcomes. The aim of this study was to describe trends in incidence and prevalence of KRT among these patients as well as to compare their outcomes versus those of patients treated with KRT for diseases other than SLE., Study Design: Retrospective cohort study based on kidney registry data., Setting & Participants: Patients recorded in 14 registries of patients receiving KRT that provided data to the European Renal Association Registry between 1992 and 2016., Predictor: SLE as cause of kidney failure., Outcomes: Incidence and prevalence of KRT, patient survival while receiving KRT, patient and graft survival after kidney transplant, and specific causes of death., Analytical Approach: Kaplan-Meier methods and Cox regression models were fit to compare patient survival between the SLE and non-SLE groups, overall KRT, dialysis, and patient and graft survival after kidney transplant., Results: In total, 1,826 patients commenced KRT for kidney failure due to SLE, representing an incidence of 0.80 per million population (pmp) per year. The incidence remained stable during the study period (annual percent change, 0.1% [95% CI, -0.6% to 0.8%]). Patient survival among patients with SLE receiving KRT was similar to survival in the comparator group (hazard ratio [HR], 1.11 [95% CI, 0.99-1.23]). After kidney transplant, the risk of death was greater among patients with SLE than among patients in the comparator group (HR, 1.25 [95% CI, 1.02-1.53]), whereas the risk of all-cause graft failure was similar (HR, 1.09 [95% CI, 0.95-1.27]). Ten-year patient overall survival during KRT and patient and graft survival after kidney transplant improved over the study period (HRs of 0.71 [95% CI, 0.56-0.91], 0.43 [95% CI, 0.27-0.69], and 0.60 [95% CI, 0.43-0.84], respectively). Patients with SLE receiving KRT were significantly more likely to die of infections (24.8%) than patients in the comparator group (16.9%; P < 0.001)., Limitations: No data were available on extrarenal manifestations of SLE, drug treatments, comorbidities, kidney transplant characteristics, or relapses of SLE., Conclusions: The prognosis of patients with SLE receiving KRT has improved over time. Survival of patients with SLE who required KRT was similar compared with patients who required KRT for other causes of kidney failure. Survival following kidney transplants was worse among patients with SLE., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with kidney failure requiring KRT are at high risk of complications and death following SARS-CoV-2 infection, with variable antibody responses to vaccination reported. We investigated the effects of COVID-19 vaccination on the incidence of infection, hospitalization, and death from COVID-19 infection., Methods: The study design was an observational data linkage cohort study. Multiple health care datasets were linked to ascertain all SARS-CoV-2 testing, vaccination, hospitalization, and mortality data for all patients treated with KRT in Scotland from the start of the pandemic over a period of 20 months. Descriptive statistics, survival analyses, and vaccine effectiveness were calculated., Results: As of September 19, 2021, 93% ( n =5281) of the established KRT population in Scotland had received two doses of an approved SARS-CoV-2 vaccine. Over the study period, there were 814 cases of SARS-CoV-2 infection (15.1% of the KRT population). Vaccine effectiveness rates against infection and hospitalization were 33% (95% CI, 0 to 52) and 38% (95% CI, 0 to 57), respectively. Within 28 days of a SARS-CoV-2-positive PCR test, 9.2% of fully vaccinated individuals died (7% patients on dialysis and 10% kidney transplant recipients). This compares to <0.1% of the vaccinated general Scottish population admitted to the hospital or dying due to COVID-19 during that period., Conclusions: These data demonstrate that a primary vaccine course of two doses has limited effect on COVID-19 infection and its complications in patients with KRT. Adjunctive strategies to reduce risk of both COVID-19 infection and its complications in this population are urgently required., (Copyright © 2022 by the American Society of Nephrology.)

Background: Acute kidney disease (AKD) is a proposed definition for acute kidney injury (AKI) lasting 7 days or longer. Little has been reported regarding characteristics of patients with AKD and their short- and long-term outcomes. We describe the epidemiology and risk factors for AKD and outcomes following AKD., Methods: This retrospective observational cohort study identified patients aged 16 or older admitted to the Glasgow Royal Infirmary and Queen Elizabeth University Hospital intensive care units (ICUs) in Scotland between 1st July 2015 and 30th June 2018. Baseline serum creatinine and subsequent values were used to identify patients with de-novo kidney injury (DNKI). Patients with recovery prior to day 7 were classified as AKI; recovery at day 7 or beyond was classified as AKD. Outcomes were in-hospital and long-term mortality, and proportion of major adverse kidney events (MAKEs). Multivariable logistic regression was used to identify risk factors for AKD. A Cox proportional hazards model was used to identify factors associated with long-term outcomes., Findings: Of the 5,334 patients admitted to ICU who were assessed for DNKI, 1,620 (30·4%) suffered DNKI and of these, 403 (24·9%) met AKD criteria; 984 (60·7%) were male and the median age was 60·0 (IQR=48·0-72·0). Male sex, sepsis and lower baseline estimated glomerular filtration rate (eGFR) were associated with development of AKD. In-ICU (16·1%vs6·2%) and in-hospital (26·1%vs11·6%) mortality rates were significantly higher in AKD patients than AKI patients. Long-term survival was not different for AKD patients (HR=1·16; p -value=0·261) but AKD was associated with subsequent MAKEs (OR=1·25)., Interpretation: One in four ICU patients with DNKI met AKD criteria. These patients had an increased risk of short-term mortality and long-term MAKEs. Whilst the trend for long-term survival was lower, this was not significantly different from shorter-term AKI patients. Patients with AKD during their ICU stay should be identified to initiate interventions to reduce risk of future MAKEs., Funding: No funding was associated with this study., Competing Interests: PM declares grants from Boehringer Ingelheim, and payment received from Vifor, Novartis, Napp, Astrazeneca, Pharmacosmos and Astellas during the study period: none of the above were for work related to the above manuscript. All other authors declare no conflicts of interest., (© 2022 The Author(s).)

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Many western countries used shielding (extended self-isolation) of people presumed to be at high-risk from COVID-19 to protect them and reduce healthcare demand. To investigate the effectiveness of this strategy, we linked family practitioner, prescribing, laboratory, hospital and death records and compared COVID-19 outcomes among shielded and non-shielded individuals in the West of Scotland. Of the 1.3 million population, 27,747 (2.03%) were advised to shield, and 353,085 (26.85%) were classified a priori as moderate risk. COVID-19 testing was more common in the shielded (7.01%) and moderate risk (2.03%) groups, than low risk (0.73%). Referent to low-risk, the shielded group had higher confirmed infections (RR 8.45, 95% 7.44-9.59), case-fatality (RR 5.62, 95% CI 4.47-7.07) and population mortality (RR 57.56, 95% 44.06-75.19). The moderate-risk had intermediate confirmed infections (RR 4.11, 95% CI 3.82-4.42) and population mortality (RR 25.41, 95% CI 20.36-31.71) but, due to their higher prevalence, made the largest contribution to deaths (PAF 75.30%). Age ≥ 70 years accounted for 49.55% of deaths. In conclusion, in spite of the shielding strategy, high risk individuals were at increased risk of death. Furthermore, to be effective as a population strategy, shielding criteria would have needed to be widely expanded to include other criteria, such as the elderly., (© 2021. The Author(s).)

Objectives: Patients requiring haemodialysis are at increased risk of serious illness with SARS-CoV-2 infection. To improve the understanding of transmission risks in six Scottish renal dialysis units, we utilised the rapid whole-genome sequencing data generated by the COG-UK consortium., Methods: We combined geographical, temporal and genomic sequence data from the community and hospital to estimate the probability of infection originating from within the dialysis unit, the hospital or the community using Bayesian statistical modelling and compared these results to the details of epidemiological investigations., Results: Of 671 patients, 60 (8.9%) became infected with SARS-CoV-2, of whom 16 (27%) died. Within-unit and community transmission were both evident and an instance of transmission from the wider hospital setting was also demonstrated., Conclusions: Near-real-time SARS-CoV-2 sequencing data can facilitate tailored infection prevention and control measures, which can be targeted at reducing risk in these settings., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Recent World Health Organization guidance has aimed to provide pragmatic guidance acknowledging the role of sequential nasopharyngeal swabs taken >24 hours apart for SARS-CoV-2 in high-risk populations. Patients with chronic kidney disease (CKD) are known to have an altered immune milieu which may be associated with a delay in viral clearance. Here, a cross-sectional observational study of 138 patients admitted with SARS-CoV-2 infection at two large regional hospitals in Scotland, UK examined the median time to two consecutive negative nasopharyngeal swabs for SARS-CoV-2 in an inpatient population. The median time from admission to the first of two consecutive negative nasopharyngeal swabs was 18 days (range = 1-44) in patients with CKD, compared with 11 days (range: 1-71) in patients without CKD (P = .0007). Multivariable linear regression analysis using explanatory variables of age, sex, SARS-CoV-2 disease severity, key comorbidities and renal function showed that declining estimated glomerular filtration rate was independently associated with prolonged time to viral clearance. Our data suggest that patients with CKD who are admitted to hospital with SARS-CoV-2 take longer to achieve sequential negative nasopharyngeal swab reverse transcription-polymerase chain reaction results than those without CKD. This has implications for renal service provision, discharge planning and hospital capacity as well as a direct impact on patients due to extended hospital stay, anxiety and stigmatisation., (© 2020 Asian Pacific Society of Nephrology.)

Background: Acute kidney injury is associated with high mortality, and the optimal time to start renal replacement therapy for acute kidney injury is unknown despite several randomised controlled trials on the subject. We performed a systematic review and meta-analysis to assess the effect of earlier initiation of renal replacement therapy for acute kidney injury on mortality and reported secondary outcomes., Methods: All literature in databases EMBASE, MEDLINE and CENTRAL was searched from January 1970 to March 2019 using terms related to renal replacement therapy, timing and randomised controlled trials. All randomised controlled trials with 25 or more adult participants suffering from acute kidney injury comparing timing of renal replacement therapy were included. The results of the selected studies were pooled and expressed in terms of risk ratios (RR) and 95% confidence intervals (95% CI) using a random effects model., Results: A total of 7008 records were identified; 94 were selected for full text review of which 10 were included in the final meta-analysis. The 10 studies comprised 1956 participants (989 'early' group; 967 'late' group) with 918 total deaths; the analysis demonstrated no significant differences between the 'early' and 'late' renal replacement therapy groups (RR = 0.98 (95% CI = 0.84, 1.15)) for mortality. No significant differences between groups were evident for period-wise mortality; dialysis dependence; recovery of renal function; length of intensive care unit or hospital stay; or number of renal replacement therapies, mechanical ventilation and vasopressor-free days., Conclusions: Current evidence does not support the use of early renal replacement therapy for patients with acute kidney injury. Data from ongoing and future randomised controlled trials are required to strengthen the evidence base in the area., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Intensive Care Society 2020.)

Background: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown., Methods: To determine if vitamin K supplementation might improve arterial stiffness in patients in CKD, we conducted a parallel-group, double-blind, randomized trial in participants aged 18 or older with CKD stage 3b or 4 (eGFR 15-45 ml/min per 1.73 m 2 ). We randomly assigned participants to receive 400 μ g oral vitamin K2 or matching placebo once daily for a year. The primary outcome was the adjusted between-group difference in carotid-femoral pulse wave velocity at 12 months. Secondary outcomes included augmentation index, abdominal aortic calcification, BP, physical function, and blood markers of mineral metabolism and vascular health. We also updated a recently published meta-analysis of trials to include the findings of this study., Results: We included 159 randomized participants in the modified intention-to-treat analysis, with 80 allocated to receive vitamin K and 79 to receive placebo. Mean age was 66 years, 62 (39%) were female, and 87 (55%) had CKD stage 4. We found no differences in pulse wave velocity at 12 months, augmentation index at 12 months, BP, B-type natriuretic peptide, or physical function. The updated meta-analysis showed no effect of vitamin K supplementation on vascular stiffness or vascular calcification measures., Conclusions: Vitamin K2 supplementation did not improve vascular stiffness or other measures of vascular health in this trial involving individuals with CKD., Clinical Trial Registry Name and Registration Number: Vitamin K therapy to improve vascular health in patients with chronic kidney disease, ISRCTN21444964 (www.isrctn.com)., (Copyright © 2020 by the American Society of Nephrology.)

Background: Infection with the severe acute respiratory coronavirus 2 (SARS-CoV-2) has led to a worldwide pandemic with coronavirus disease 2019 (COVID-19), the disease caused by SARS-CoV-2, overwhelming healthcare systems globally. Preliminary reports suggest a high incidence of infection and mortality with SARS-CoV-2 in patients receiving kidney replacement therapy (KRT). The aims of this study are to report characteristics, rates and outcomes of all patients affected by infection with SARS-CoV-2 undergoing KRT in Scotland., Methods: Study design was an observational cohort study. Data were linked between the Scottish Renal Registry, Health Protection Scotland and the Scottish Intensive Care Society Audit Group national data sets using a unique patient identifier (Community Health Index (CHI)) for each individual by the Public Health and Intelligence unit of Public Health, Scotland. Descriptive statistics and survival analyses were performed., Results: During the period 1st March 2020 to 31st May 2020, 110 patients receiving KRT tested positive for SARS-CoV-2 amounting to 2% of the prevalent KRT population. Of those affected, 86 were receiving haemodialysis or peritoneal dialysis and 24 had a renal transplant. Patients who tested positive were older and more likely to reside in more deprived postcodes. Mortality was high at 26.7% in the dialysis patients and 29.2% in the transplant patients., Conclusion: The rate of detected SARS-CoV-2 in people receiving KRT in Scotland was relatively low but with a high mortality for those demonstrating infection. Although impossible to confirm, it appears that the measures taken within dialysis units coupled with the national shielding policy, have been effective in protecting this population from infection.

Background: Static postural balance performance is often impaired in people receiving haemodialysis (HD) for the treatment of stage-5 chronic kidney disease (CKD-5). However, the question as to whether lower postural balance is associated with adverse clinical outcomes such as falls has not been addressed yet., Research Question: We conducted a prospective cohort study to explore the association between static postural balance and falls in people receiving HD. We hypothesised that higher postural sway would be associated with increased odds of falling., Methods: Seventy-five prevalent CKD-5 patients receiving HD (age: 61.8 ± 13.4 years) from three Renal Units were enrolled in this prospective cohort study. At baseline, postural balance was assessed with a force platform in eyes open (EO) and eyes closed (EC) conditions. Centre of pressure (CoP) measures of range, velocity and area were taken for the analysis. Falls experienced by study participants were prospectively recorded during 12 months of follow-up. Secondary outcomes included timed-up and go, five-repetition sit-to-stand test and the Tinetti falls efficacy scale (FES)., Results: In multivariable logistic regression analysis, higher CoP range in medial-lateral direction during EC was associated with increased odds of falling (OR: 1.04, 95 %CI: 1.00-1.07, p = 0.036). In ROC curve analysis, CoP velocity in EO exhibited the greatest prognostic accuracy (AUC: 0.69, 95 %CI: 0.55-0.82), however this was not statistically different from CoP measures of area and range. None of the postural balance measures exceeded the prognostic accuracy of the FES (AUC: 0.70, 95 %CI: 0.58-0.83, p = 0.005)., Significance: This prospective cohort study showed that higher postural sway in medial-lateral direction was associated with increased odds of falling in people receiving HD. CoP measures of range, velocity and area displayed similar prognostic value in discriminating fallers from non-fallers. The overall utility of static posturography to detect future fall-risk may be limited in a clinical setting., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Although measuring albuminuria is the preferred method for defining and staging chronic kidney disease (CKD), total urine protein or dipstick protein is often measured instead., Objective: To develop equations for converting urine protein-creatinine ratio (PCR) and dipstick protein to urine albumin-creatinine ratio (ACR) and to test their diagnostic accuracy in CKD screening and staging., Design: Individual participant-based meta-analysis., Setting: 12 research and 21 clinical cohorts., Participants: 919 383 adults with same-day measures of ACR and PCR or dipstick protein., Measurements: Equations to convert urine PCR and dipstick protein to ACR were developed and tested for purposes of CKD screening (ACR ≥30 mg/g) and staging (stage A2: ACR of 30 to 299 mg/g; stage A3: ACR ≥300 mg/g)., Results: Median ACR was 14 mg/g (25th to 75th percentile of cohorts, 5 to 25 mg/g). The association between PCR and ACR was inconsistent for PCR values less than 50 mg/g. For higher PCR values, the PCR conversion equations demonstrated moderate sensitivity (91%, 75%, and 87%) and specificity (87%, 89%, and 98%) for screening (ACR >30 mg/g) and classification into stages A2 and A3, respectively. Urine dipstick categories of trace or greater, trace to +, and ++ for screening for ACR values greater than 30 mg/g and classification into stages A2 and A3, respectively, had moderate sensitivity (62%, 36%, and 78%) and high specificity (88%, 88%, and 98%). For individual risk prediction, the estimated 2-year 4-variable kidney failure risk equation using predicted ACR from PCR had discrimination similar to that of using observed ACR., Limitation: Diverse methods of ACR and PCR quantification were used; measurements were not always performed in the same urine sample., Conclusion: Urine ACR is the preferred measure of albuminuria; however, if ACR is not available, predicted ACR from PCR or urine dipstick protein may help in CKD screening, staging, and prognosis., Primary Funding Source: National Institute of Diabetes and Digestive and Kidney Diseases and National Kidney Foundation.

Background: In Scotland, standard maintenance immunosuppression following kidney transplantation consists of mycophenolate (MPA), tacrolimus and prednisolone irrespective of recipient age. We analyzed the tolerability of this immunosuppression regimen and the association with transplant outcomes., Methods: A national, multicentre retrospective analysis of patients transplanted in 2015 and 2016, comparing graft function, acute rejection, significant infection rates and immunosuppression dosing between patients aged 18 and 59 years (Group 1) and ≥60 years (Group 2)., Results: Of the 490 patients, 26% were aged ≥60 years. Acute rejection (AR) rates at 1 year were 15% and 11% in Groups 1 and 2, respectively. Full-dose MPA was poorly tolerated with 53% in Group 1 and 77% in Group 2 requiring dose reduction or cessation. Female gender and age ≥60 years were independent predictors for MPA dose changes. One year following MPA dose reduction, AR risk was low (5%) in Group 2, however, those remaining on full dose MPA had a 79% increased rate of serious infections., Conclusion: The majority of renal transplant recipients aged ≥60 fail to tolerate full-dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full-dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate., (© 2020 Asian Pacific Society of Nephrology.)

Background: This article presents a summary of the 2017 Annual Report of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 37 countries., Methods: The ERA-EDTA Registry received individual patient data on patients undergoing RRT for ESRD in 2017 from 32 national or regional renal registries and aggregated data from 21 registries. The incidence and prevalence of RRT, kidney transplantation activity and survival probabilities of these patients were calculated., Results: In 2017, the ERA-EDTA Registry covered a general population of 694 million people. The incidence of RRT for ESRD was 127 per million population (pmp), ranging from 37 pmp in Ukraine to 252 pmp in Greece. A total of 62% of patients were men, 52% were ≥65 years of age and 23% had diabetes mellitus as the primary renal disease. The treatment modality at the onset of RRT was haemodialysis for 85% of patients. On 31 December 2017, the prevalence of RRT was 854 pmp, ranging from 210 pmp in Ukraine to 1965 pmp in Portugal. The transplant rate in 2017 was 33 pmp, ranging from 3 pmp in Ukraine to 103 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2008-12, the unadjusted 5-year patient survival probability for all RRT modalities combined was 50.8%., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Low levels of physical activity are implicated in low life expectancies of people receiving maintenance haemodialysis. Accelerometers are increasingly being used to quantify activity behaviours of this population but guidance to quality-assure such data is lacking. The objective of this study was to provide data processing and reduction recommendations to ensure accelerometer-derived outcomes are sufficiently reliable for interpretative analysis., Methods: Seventy people receiving maintenance haemodialysis (age 55.9 ± 15.7 years, 34% women, 23% diabetic) from a single outpatient renal unit volunteered for the study. Participants wore Actigraph GT3x and ActivPAL monitors during waking hours over seven days. Reliability of accelerometer output (normalised to wear-time) was assessed via intraclass correlation coefficient (ICC). The Spearman-Brown prophecy formula was subsequently applied to the ICCs to derive the minimum required accelerometer wear-time for each behavioural outcome., Results: Monitor wear compliance was greater on dialysis compared to non-dialysis days (90% v 77%). Participants were significantly more active on non-dialysis days compared to dialysis days but there were no significant differences in estimated behaviours between days within the same condition. Average measure ICCs for all accelerometer outcomes were high (range 0.76-0.96). Computations indicated that habitual physical activity and sedentary behaviour could be estimated with a minimum reliability level of 0.80 from one dialysis day and two non-dialysis days, and at least eight hours monitor wear per day. Applying this rubric allowed 90% of participant data to be retained for further analysis., Conclusions: Regardless of accelerometer, one dialysis and two non-dialysis days data with a minimum of eight hours wear each day should enable habitual activity of people receiving maintenance haemodialysis to be characterised with acceptable reliability. These recommendations reconcile the tension between wear-time criteria stringency and retention of an adequately representative sample.

Background: Data on long-term outcomes in children who have received renal replacement therapy (RRT) for end-stage renal disease are limited., Methods: We studied long-term survival and incidence of fatal and nonfatal cardiovascular disease (CVD) events and determinants of these outcomes in children who initiated RRT between 1961 and 2013 using data from the Scottish Renal Registry (SRR). Linkage to morbidity records was available from 1981., Results: A total of 477 children of whom 55% were boys, almost 50% had congenital urinary tract disease (CAKUT), 10% received a transplant as the first mode of RRT and almost 60% were over 11 years of age at start of RRT were followed for a median of 17.8 years (interquartile range (IQR) 8.7-26.6 years). Survival was 87.3% (95% confidence interval (CI) 84.0-90.1) at 10 years and 77.6% (95% CI 73.3-81.7) at 20 years. During a median follow-up of 14.96 years (IQR 7.1-22.9), 20.9% of the 381 patients with morbidity data available had an incident of CVD event. Age < 2 years at start of RRT, receiving dialysis rather than a kidney transplant and primary renal disease (PRD) other than CAKUT or glomerulonephritis (GN), were associated with a higher risk of all-cause mortality. Male sex, receiving dialysis rather than a kidney transplant and PRD other than CAKUT or GN, was associated with a higher risk of CVD incidence., Conclusions: Mortality and CVD incidence among children receiving RRT are high. PRD and RRT modality were associated with increased risk of both all-cause mortality and CVD incidence.

Background: Stage 5 chronic kidney disease (CKD-5) patients on haemodialysis (HD) are at high risk of accidental falls. Previous research has shown that frailty is one of the primary contributors to the increased risk of falling in this clinical population. However, HD patients often present with abnormalities of cardiovascular function such as baroreflex impairment and orthostatic dysregulation of blood pressure (BP) which may also be implicated in the aetiology of falling. Therefore, we aimed to explore the relative importance of frailty and cardiovascular function as potential exercise-modifiable predictors of falls in these patients., Methods: Ninety-three prevalent CKD-5 patients on HD from three Renal Units were recruited for this prospective cohort study, which was conducted between October 2015 and August 2018. At baseline, frailty status was assessed using the Fried's frailty phenotype, while physical function was evaluated through timed up and go (TUG), five repetitions chair sit-to-stand (CSTS-5), objectively measured physical activity, and maximal voluntary isometric strength. Baroreflex and haemodynamic function at rest and in response to a 60° head-up tilt test (HUT-60°) were also assessed by means of the Task Force Monitor. The number of falls experienced was recorded once a month during 12 months of follow-up., Results: In univariate negative binomial regression analysis, frailty (RR: 4.10, 95%CI: 1.60-10.51, p = 0.003) and other physical function determinants were associated with a higher number of falls. In multivariate analysis however, only worse baroreflex function (RR: 0.96, 95%CI: 0.94-0.99, p = 0.004), and orthostatic decrements of BP to HUT-60° (RR: 0.93, 95%CI: 0.87-0.99, p = 0.033) remained significantly associated with a greater number of falls. Eighty falls were recorded during the study period and the majority of them (41.3%) were precipitated by dizziness symptoms, as reported by participants., Conclusions: This prospective study indicates that cardiovascular mechanisms implicated in the short-term regulation of BP showed a greater relative importance than frailty in predicting falls in CKD-5 patients on HD. A high number of falls appeared to be mediated by a degree of cardiovascular dysregulation, as evidenced by the predominance of self-reported dizziness symptoms., Trial Registration: ClinicalTrials.gov (trial registration ID: NCT02392299; date of registration: March 18, 2015).

Background: Previous US studies have indicated that haemodialysis with ≥6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients., Methods: We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association-European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5-4 h/treatment), EHD (three times weekly, ≥6 h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders., Results: From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.1 ± 0.8 h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 ± 0.2 h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62-0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71-0.90)]., Conclusions: EHD is associated with better survival in European patients treated with haemodialysis three times weekly., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background and Objectives: More men than women undergo kidney replacement therapy (KRT) despite a larger number of women being affected by CKD. The aim of this multinational European study was to explore whether there might be historic and geographic trends in sex-specific incidence and prevalence of various KRT modalities., Design, Setting, Participants, & Measurements: We assessed sex-specific differences in KRT incidence and prevalence using data from nine countries reporting to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry for at least 40 years, during the period 1965-2015. Sex distribution data were compared with the European general population (Eurostat). Statistical methodology included basic descriptive statistics, incidence and prevalence calculations per million population (pmp), as well as their male-to-female ratios. Analyses were stratified by age group and diabetic status., Results: We analyzed data from 230,378 patients receiving KRT (38% women). For all KRT modalities, the incidence and prevalence rates were consistently higher in men than women. For example, the KRT incidence increased from 8 pmp in 1965-1974 to 98 pmp in 2005-2015 in women, whereas it rose from 12 to 173 pmp in men during the same period. Male-to-female ratios, calculated for incident and prevalent KRT patients, increased with age (range 1.2-2.4), showing consistency over decades and for individual countries, despite marked changes in primary kidney disease (diabetes more prevalent than glomerulonephritis in recent decades). The proportion of kidney transplants decreased less with age in incident and prevalent men compared with women on KRT. Stratified analysis of patients who were diabetic versus nondiabetic revealed that the male-to-female ratio was markedly higher for kidney transplantation in patients with diabetes., Conclusions: Since the beginning of KRT programs reporting to the ERA-EDTA Registry since the 1960s, fewer women than men have received KRT. The relative difference between men and women initiating and undergoing KRT has remained consistent over the last five decades and in all studied countries., (Copyright © 2019 by the American Society of Nephrology.)

Background: Proton pump inhibitors (PPIs) are associated with acute tubulointerstitial nephritis and there are reports associating their use with the development of chronic kidney disease (CKD)., Aim: To determine if PPI use is associated with major adverse renal events (MARE) in patients with CKD., Design: Observational cohort study comprising patients with CKD attending secondary care renal clinics from 1 January 2006 until 31 December 2016., Methods: We collated baseline clinical, socio-demographic and biochemical data at start of PPI (PPI group) or study inception (control group). MARE was considered a composite of doubling of creatinine or end-stage renal disease. Association between PPI exposure and progression to MARE was assessed by cause-specific hazards competing risk survival analysis., Results: There were 3824 patients with CKD included in the analyses of whom 1195 were prescribed a PPI. The PPI group was younger (64.8 vs. 67.0 years, P < 0.001), with lower estimated glomerular filtration rate (eGFR) (30 vs. 35 ml/min, P < 0.001) and more proteinuria (64 vs. 48 mg/mmol, P < 0.001). PPI use was associated with progression to MARE on multivariable adjustment (hazard ratio 1.13 [95% confidence interval 1.02-1.25], P = 0.021). Other factors significantly associated with progression to MARE were higher systolic blood pressure, lower eGFR, greater proteinuria, congestive cardiac failure and diabetes. Hypomagnesaemia was more common in the PPI group (39.5 vs. 18.9%, P < 0.001)., Conclusion: PPI use was associated with progression to MARE, but not death in patients with CKD after adjusting for factors known to predict declining renal function, including lower eGFR, proteinuria and comorbidities. A prospective cohort study is required to validate these findings., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Aim: To examine international time trends in the incidence of renal replacement therapy (RRT) for end-stage renal disease (ESRD) by primary renal disease (PRD)., Methods: Renal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression., Results: There was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = -0.9; 95%CI -1.3; -0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = -1.8; 95%CI -3.3; -0.3), Canada (AAPC = -2.9; 95%CI -4.4; -1.5) and Europe (AAPC = -1.1; 95%CI -2.1; -0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2-16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea., Conclusion: Large international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD., (© 2018 Asian Pacific Society of Nephrology.)

Background: Stroke is common in patients with end-stage renal disease (ESRD) treated with hemodialysis (HD) and associated with high mortality rate. In the general population, atrial fibrillation (AF) is a major risk factor for stroke and therapeutic anticoagulation is associated with risk reduction, whereas in ESRD the relationship is less clear., Objective: The purpose of this study is to demonstrate the influence of AF on stroke rates and probability in those on HD following competing risk analyses., Design: A national record linkage cohort study., Setting: All renal and stroke units in Scotland, UK., Patients: All patients with ESRD receiving HD within Scotland from 2005 to 2013 (follow-up to 2015)., Measurements: Demographic, clinical, and laboratory data were linked between the Scottish Renal Registry, Scottish Stroke Care Audit, and hospital discharge data. Stroke was defined as a fatal or nonfatal event and mortality derived from national records., Methods: Associations for stroke were determined using competing risk models: the cause-specific hazards model and the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of all stroke, ischemic stroke, and first-ever stroke., Results: Of 5502 patients treated with HD with 12 348.6-year follow-up, 363 (6.6%) experienced stroke. The stroke incidence rate was 26.7 per 1000 patient-years. Multivariable regression on the cause-specific hazard for stroke demonstrated age, hazard ratio (HR) (95% confidence interval [CI]) = 1.04 (1.03-1.05); AF, HR (95% CI) = 1.88 (1.25-2.83); prior stroke, HR (95% CI) = 2.29 (1.48-3.54), and diabetes, HR (95% CI) = 1.92 (1.45-2.53); serum phosphate, HR (95% CI) = 2.15 (1.56-2.99); lower body weight, HR (95% CI) = 0.99 (0.98-1.00); lower hemoglobin, HR (95% CI) = 0.88 (0.77-0.99); and systolic blood pressure (BP), HR (95% CI) = 1.01 (1.00-1.02), to be associated with an increased stroke rate. In contrast, the subdistribution HRs obtained following Fine and Gray regression demonstrated that AF, weight, and hemoglobin were not associated with stroke risk. In both models, AF was significantly associated with nonstroke death., Limitations: Our analyses derive from retrospective data sets and thus can only describe association not causation. Data on anticoagulant use are not available., Conclusions: The incidence of stroke in HD patients is high. The competing risk of "prestroke" mortality affects the relationship between AF and risk of future stroke. Trial designs for interventions to reduce stroke risk in HD patients, such as anticoagulation for AF, should take account of competing risks affecting associations between risk factors and outcomes., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2019.)

Genetic variation across the human leukocyte antigen loci is known to influence renal-transplant outcome. However, the impact of genetic variation beyond the human leukocyte antigen loci is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with posttransplant eGFR at different time-points, out to 5 years posttransplantation. We conducted GWAS meta-analyses across 10 844 donors and recipients from five European ancestry cohorts. We also analyzed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with nontransplant eGFR, on posttransplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1-year posttransplant. Thirty-two percent of the variability in eGFR at 1-year posttransplant was explained by our model containing clinical covariates (including weights for death/graft-failure), principal components and combined donor-recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR posttransplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a posttransplant context. Despite PRS being a significant predictor of eGFR posttransplant, the effect size of common genetic factors is limited compared to clinical variables., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objective: The predicted outcomes of autogenous arteriovenous (AV) hemodialysis access creation are predominantly based on historical data; however, both the hemodialysis population and clinical practices have changed significantly during the last decade. This study examined contemporary AV access clinical use and patencies., Methods: A multicenter observational cohort study was performed of all new AV accesses created in Scotland in 2015. The primary end point was efficacy assessed by successful AV access use for a minimum of 30 days and primary, primary assisted, and secondary patency at 1 year. Data obtained included all interventions to maintain or to restore patency. Predictors of patency loss including demographics, comorbid conditions, dialysis status, AV access location, duplex ultrasound surveillance, procedures, prior access, and antiplatelets were assessed. Kaplan-Meier and competing risks analyses were performed to estimate the probability of AV access failure. All patients were followed up for at least 1 year or had a censoring event., Results: A total of 582 AV accesses were created in 537 patients (mean age, 60 [standard deviation, 14] years; 60% men; 42% with diabetes) in nine adult renal centers. Mean follow-up was 11.8 (standard deviation, 7.6) months. By the end of the follow-up, 322 (55.3%) AV accesses were successfully used for dialysis. At 1 year, 48% (95% confidence interval [CI], 44-52) of AV accesses had primary patency, (95% CI, 63-71) had primary assisted patency, and 69% (95% CI, 65-73) had secondary patency. The leading cause of primary patency loss was primary failure (30%). An average of 0.48 intervention per patient-year was required to maintain patency. On multivariable analysis, patency was better for an upper arm than for a forearm AV access (1-year secondary patency of upper arm vs forearm AV accesses, 74% vs 58%). The cumulative hazard and incident functions for AV access failure were 31% (95% CI, 27-35) and 23% (95% CI, 20-27) at 1 year, respectively., Conclusions: Despite advances in recent years with preoperative vessel assessment and surveillance, patency rates have not improved, with primary failure remaining the major obstacle. Competing events should be taken into consideration; otherwise, biases may occur with overestimation of the probability of AV access failure., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Renal transplant recipients have an increased risk of non-melanoma skin cancer (NMSC) compared to in the general population. Here, we show polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of NMSC in a general, nontransplant setting, can predict risk of, and time to posttransplant skin cancer. Genetic variants, reaching predefined P-value thresholds were chosen from published squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) nontransplant GWAS. Using these GWAS, BCC and SCC PRS were calculated for each sample across three European ancestry renal transplant cohorts (n = 889) and tested as predictors of case:control status and time to NMSC posttransplant. BCC PRS calculated at P-value threshold 1 × 10 -5 was the most significant predictor of case:control status of NMSC posttransplant (OR = 1.61; adjusted P = .0022; AUC [full model adjusted for clinical predictors and PRS] = 0.81). SCC PRS at P-value threshold 1 × 10 -5 was the most significant predictor of time to posttransplant NMSC (adjusted P = 9.39 × 10 -7 ; HR = 1.41, concordance [full model] = 0.74). PRS of nontransplant NMSC is predictive of case:control status and time to NMSC posttransplant. These results are relevant to how genomics can risk stratify patients to help develop personalized treatment regimens., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Rationale & Objective: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT., Study Design: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes., Setting & Participants: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013., Predictor: Scleroderma as the identified cause of ESRD., Outcomes: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation., Analytical Approach: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression., Results: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both P<0.001), though time required to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups., Limitations: No data for extrarenal manifestations, treatment, or recurrence., Conclusions: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Socioeconomic deprivation (SED) influences likelihood of pre-emptive kidney transplantation (PET), but the mechanisms behind this are unclear. We explored the relationships between SED and patient characteristics at referral, which might explain this discrepancy. A retrospective cohort study was performed. SED was measured by Scottish Index of Multiple Deprivation (SIMD). Logistic regression evaluated predictors of PET. A competing risks survival analysis evaluated the interaction between SED and progression to end-stage kidney disease (ESKD) and death. Of 7765 patients with follow-up of 5.69 ± 6.52 years, 1298 developed ESKD requiring RRT; 113 received PET, 64 of which were from live donors. Patients receiving PET were "less deprived" with higher SIMD (5 ± 7 vs. 4 ± 5; P = 0.003). This appeared independent of overall comorbidity burden. SED was associated with a higher risk of death but not ESKD. Higher SIMD decile was associated with a higher likelihood of PET (OR 1.14, 95% CI 1.06, 1.23); the presence of diabetes and malignancy also reduced PET. SED was associated with reduced likelihood of PET after adjustment for baseline comorbidity, and this was not explained by risk of death or faster progression to ESKD. Education and outreach into transplantation should be augmented in areas with higher deprivation., (© 2018 Steunstichting ESOT.)

Background: Stage 5 chronic kidney disease patients on haemodialysis (HD) often present with dizziness and pre-syncopal events as a result of the combined effect of HD therapy and cardiovascular disease. The dysregulation of blood pressure (BP) during orthostasis may be implicated in the aetiology of falls in these patients. Therefore, we explored the relationship between baroreflex function, the haemodynamic responses to a passive orthostatic challenge, and falls in HD patients., Methods: Seventy-six HD patients were enrolled in this cross-sectional study. Participants were classified as "fallers" and "non-fallers" and completed a passive head up tilting to 60o (HUT-60°) test on an automated tilt table. ECG signals, continuous and oscillometric BP measurements and impedance cardiography were recorded. The following variables were derived from these measurements: heart rate (HR) stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR), number of baroreceptor events, and baroreceptor effectiveness index (BEI)., Results: The forty-four participants who were classified as fallers (57.9%) had a lower number of baroreceptor events (6.5±8.5 vs 14±16.7, p = .027) and BEI (20.8±24.2% vs 33.4±23.3%, p = .025). In addition, fallers experienced a significantly larger drop in systolic (-6.4±10.9 vs -0.4±7.7 mmHg, p = .011) and diastolic (-2.7±7.3 vs 1.8±6 mmHg, p = .027) oscillometric BP from supine to HUT-60° compared with non-fallers. None of the variables taken for the analysis were significantly associated with falls in multivariate logistic regression analysis., Conclusions: This cross-sectional comparison indicates that, at rest, HD patients with a positive history of falls present with a lower count of baroreceptor sequences and BEI. Short-term BP regulation warrants further investigation as BP drops during a passive orthostatic challenge may be implicated in the aetiology of falls in HD., Competing Interests: The authors have declared that no competing interests exist.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries., Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16  years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes., Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75., Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear., Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group., Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke., Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis.

Background: The modality by which haemodialysis (HD) is delivered [arteriovenous fistula (AVF), arteriovenous graft (AVG) or central venous catheter (CVC)] varies widely and is influenced by clinical evidence, patient factors and the prevailing service configuration. The aim of this study was to determine the outcome and impact of access strategy on patient outcome by mapping out the HD journey in a cohort of incident patients., Methods: A 2-year cohort of consecutive incident HD patients from the point of referral for first dialysis access to completion of the first 365 days of HD was prospectively reviewed. Data were sought on access type; radiological, surgical and other access-related activity; bacteraemic events; admission rates and cumulative financial cost., Results: A total of 144 patients started RRT for the first time with HD over the 2-year period. All were followed up to 1 year after starting HD, generating a total of 47 753 observed HD days.  Activity prior to starting HD for the full cohort was found to average 0.92 arteriovenous (AV) access creation procedures, 0.40 CVC insertions, 0.14 interventional radiology procedures and 0.41 ultrasound examinations per patient. The small number of patients who started on an AVG had a tendency towards higher pre-HD surgical and imaging activity than those who started on an AVF or CVC.  Activity after starting HD varied greatly with the access type used at the start of HD, with AVF patients experiencing less hospitalization, procedure and imaging activity and financial costs compared with those who start HD with a CVC. Patients who started on an AVG had a tendency towards lower surgical activity rates and financial costs than those who started on a CVC., Conclusions: Providing, maintaining and dealing with the complications of HD vascular access places a significant burden of activity that is shared across nephrology, surgery and imaging services. A well-functioning AVF is associated with the lowest burden, whereas a failed AVF or CVC access is associated with the highest burden. Patient journeys are shaped by the vascular access that they use and we suggest that the contemporary pursuit of HD access should focus on delivering personalized access solutions.

As the median age of deceased kidney donors rises, updated knowledge of transplant outcomes from older deceased donors in differing donor-recipient age groups is required. Using ERA-EDTA Registry data we determined survival outcomes of kidney allografts donated from the same older deceased donor (55-70 years), and transplanted into one recipient younger and one recipient of similar age to the donor. The recipient pairs were divided into two groups: group 1; younger (median age: 52 years) and older (60 years) and group 2; younger (41 years) and older (60 years). A total of 1410 adults were transplanted during 2000-2007. Compared to the older recipients, the mean number of functioning graft years at 10 years was 6 months longer in the group 1 and group 2 younger recipients (P < 0.001). Ten-year graft survival was 54% and 40% for the group 1 younger and older recipients, and 60% and 49% for the group 2 younger and older recipients. Paired Cox regression analyses showed a lower risk of graft failure (group 1 younger; adjusted relative risk [RRa]:0.57, 95% CI:0.41-0.79, and group 2 younger; RRa:0.63, 95% CI:0.47-0.85) in younger recipients. Outcomes from older deceased donor allografts transplanted into differing donor-recipient age groups are better than previously reported. These allografts remain a valuable transplant resource, particularly for similar-aged recipients., (© 2017 Steunstichting ESOT.)

To what extent access to, and allocation of kidney transplants and survival outcomes in patients aged ≥75 years have changed over time in Europe is unclear. We included patients aged ≥75-84 years (termed older adults) receiving renal replacement therapy in thirteen European countries between 2005 and 2014. Country differences and time trends in access to, and allocation of kidney transplants were examined. Survival outcomes were determined by Cox regression analyses. Between 2005 and 2014, 1392 older adult patients received 1406 transplants. Access to kidney transplantation varied from ~0% (Slovenia, Greece and Denmark) to ~4% (Norway and various Spanish regions) of all older adult dialysis patients, and overall increased from 0.3% (2005) to 0.9% (2014). Allocation of kidney transplants to older adults overall increased from 0.8% (2005) to 3.2% (2014). Seven-year unadjusted patient and graft survival probabilities were 49.1% (95% confidence interval, 95% CI: 43.6; 54.4) and 41.7% (95% CI: 36.5; 46.8), respectively, with a temporal trend towards improved survival outcomes. In conclusion, in the European dialysis population aged ≥75-84 years access to kidney transplantation is low, and allocation of kidney transplants remains a rare event. Though both are increasing with time and vary considerably between countries. The trend towards improved survival outcomes is encouraging. This information can aid informed decision-making regarding treatment options., (© 2018 Steunstichting ESOT.)

Introduction: Stroke rate and mortality are greater in individuals with end-stage renal disease (ESRD) than in those without ESRD. We examined discrepancies in stroke care in ESRD patients and their influence on mortality., Methods: This is a national record linkage cohort study of hospitalized stroke individuals from 2005 to 2013. Presentation, measures of care quality (admission to stroke unit, swallow assessment, antithrombotics, or thrombolysis use), and outcomes were compared in those with and without ESRD after propensity score matching (PSM). We examined the effect of being admitted to a stroke unit on survival using Kaplan-Meier and Cox survival analyses., Results: A total of 8757 individuals with ESRD and 61,367 individuals with stroke were identified. ESRD patients (n =486) experienced stroke over 34,551.9 patient-years of follow-up; incidence rates were 25.3 (dialysis) and 4.5 (kidney transplant)/1000 patient-years. After PSM, dialysis patients were less likely to be functionally independent (61.4% vs. 77.7%; P  < 0.0001) before stroke, less frequently admitted to stroke units (64.6% vs. 79.6%; P  < 0.001), or to receive aspirin (75.3% vs. 83.2%; P  = 0.01) than non-ESRD stroke patients. There were no significant differences in management of kidney transplantation patients. Stroke with ESRD was associated with a higher death rate during admission (dialysis 22.9% vs.14.4%, P  = 0.002; transplantation: 19.6% vs. 9.3%; P  = 0.034). Managing ESRD patients in a stroke unit was associated with a lower risk of death at follow-up (hazard ratio: 0.68; 95% confidence interval: 0.55-0.84)., Conclusion: Stroke incidence is high in ESRD. Individuals on dialysis are functionally more dependent before stroke and less frequently receive optimal stroke care. After a stroke, death is more likely in ESRD patients. Acute stroke unit care may be associated with lower mortality.

Background/introduction: Patient reported outcome measures (PROMs) can evaluate the quality of health in patients with established renal failure. There is limited experience of their use within national renal registries., Aim: To describe the Scottish Renal Registry's (SRR) experience of collecting PROMS in the haemodialysis population and correlate PROMS to demographic and clinical parameters., Design: Retrospective observational cross-sectional study., Methods: Haemodialysis patients in Scotland were invited to complete the KDQOL™-36 questionnaire on the day of the annual SRR census in 2015 and 2016. Questionnaires were linked to census demographic and clinical variables., Results: In 2016, 738 questionnaires were linked to census data (39% of prevalent haemodialysis population). Response rates differed with age (≥ 65 years 42%, < 65 years 36%) [χ2P = 0.006]; duration of renal replacement therapy (<1 year 46%, ≥1 < 5 years 38%, ≥ 5 years 33%) [χ2P = 0.002] and social class (Scottish Index of Multiple Deprivation (SIMD) Class 1 32%, Class 2 41%, Class 3 40%, Class 4 48%, Class 5 40%) [χ2P < 0.001]. There were significant differences in PROMs with age, SIMD quintile and primary renal diagnosis. Achieving a urea reduction ratio of >65% and dialysing through arteriovenous access were associated with significantly higher PROMs. PROMs were not affected by haemoglobin or phosphate concentration., Discussion/conclusions: Routine collection of PROMs is feasible and can identify potentially under-recognized and treatable determinants to quality of life. The association between attaining recommended standards of care and improved PROMs is striking. Individual and population-wide strategies are required to improve PROMs., (© The Author 2017. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Background: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors., Methods: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up., Results: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture., Conclusions: The risk of symptomatic bone fracture is high in RRT patients and is ∼2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: Published registry data demonstrate longstanding variation in the utilisation of different vascular access (VA) modalities between Scottish renal units; this may reflect different clinical processes between centres. A comprehensive appraisal was undertaken to understand the processes underpinning VA creation and maintenance across Scotland., Methods: A mixed methods approach was utilised. Fifty-two semi-structured interviews were conducted with patients and clinicians in all ten, adult and paediatric, Scottish renal units. Interview transcripts were subjected to thematic analysis. Clinical activity data were prospectively collected for six weeks, and correlated with registry data., Results: VA accounts for a large clinical workload. There was significant inter-centre variation in the utilisation of different VA modalities, and patients described frustrating, dissatisfying experiences. VA creation and maintenance pathways functioned best when nephrologists, surgeons and radiologists were co-located on the same campus with close multi-disciplinary working, protected clinical time, and proactive VA maintenance. No unit routinely measured or discussed procedure outcomes or strategic aspects of their service., Conclusions: Varied clinical outcomes reflected varied clinical processes. Optimised clinical pathways, staff education and measurement of clinical outcomes may improve VA service quality and facilitate safer, more effective, patient-centred care.

Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European countries., Methods: We defined lifetime risk of RRT as the cumulative incidence of RRT up to age 90 years. We obtained RRT incidence rates per million population by 5-year age groups and sex using data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, and used these to estimate the cumulative incidence of RRT, adjusting for competing mortality risk., Results: Lifetime risk of RRT varied from 0.44% to 2.05% at age 20 years and from 0.17% to 1.59% at age 70 years across countries, and was twice as high in men as in women. Lifetime RRT risk decreased with age, ranging from an average of 0.77% to 0.44% in 20- to- 70-year-old women, and from 1.45% to 0.96% in 20- to- 70-year-old men. The lifetime risk of RRT increased slightly over the past decade, more so in men than in women. However, it appears to have stabilized or even decreased slightly in more recent years., Conclusions: The lifetime risk of RRT decreased with age, was lower in women as compared with men of equal age and varied considerably throughout Europe. Given the substantial differences in lifetime risk of RRT between the USA and Europe, country-specific estimates should be used in the evaluation and communication of the risk of RRT for potential living kidney donors., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)