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Background Coronary microvascular dysfunction (CMD) is common in end-stage renal disease (ESRD) and is an adverse prognostic marker. Coronary flow velocity reserve (CFVR) is a measure of coronary microvascular function and can be assessed using Doppler echocardiography. Reduced CFVR in ESRD has been attributed to factors such as diabetes, hypertension and left ventricular hypertrophy. The contributory role of other mediators important in the development of cardiovascular disease in ESRD has not been studied. The aim of this study was to examine the prevalence of CMD in a cohort of kidney transplant candidates and to look for associations of CMD with markers of anaemia, bone mineral metabolism and chronic inflammation. Methods Twenty-two kidney transplant candidates with ESRD were studied with myocardial contrast echocardiography, Doppler CFVR assessment and serum multiplex immunoassay analysis. Individuals with diabetes, uncontrolled hypertension or ischaemic heart disease were excluded. Results 7/22 subjects had CMD (defined as CFVR Conclusions Among kidney transplant candidates with ESRD, there is a high prevalence of CMD, despite the absence of traditional risk factors. Anaemia may be a potential driver of microvascular dysfunction in this population and requires further investigation.

Introduction For patients with end-stage renal disease (ESRD), due to the heterogeneity of the population, appropriate risk assessment approaches and strategies for further follow-up remain scarce. We aimed to conduct a pilot study for better risk stratification, applying machine learning–based classification to patients with ESRD who newly started maintenance hemodialysis. Methods We prospectively studied 101 patients with ESRD, who were new to maintenance hemodialysis therapy, between August 2016 and March 2018. Baseline values of variables such as blood and urine tests were obtained before the initiation of hemodialysis. Agglomerative hierarchical clustering was conducted with the collected continuous data. The resulting clusters were followed up for the primary outcome of 1-year mortality, as analyzed by the Kaplan-Meier survival curve with log-rank test and the Cox proportional hazard model. Results The participants were divided into 3 clusters (cluster 1, n = 62; cluster 2, n = 15; cluster 3, n = 24) by hierarchical clustering, using 46 clinical variables. Patients in cluster 3 showed lower systolic blood pressures, and lower serum creatinine and urinary liver-type fatty acid-binding protein levels, before the initiation of hemodialysis. Consequently, cluster 3 was associated with the highest 1-year mortality in the study cohort (P < 0.001), and the difference was significant after adjustment for age and sex (hazard ratio: 10.2; 95% confidence interval: 2.94–46.8, cluster 1 as reference). Conclusion In this proof-of-concept study, hierarchical clustering discovered a subgroup with a higher 1-year mortality at the initiation of hemodialysis. Applying machine learning–derived classification to patients with ESRD may contribute to better risk stratification., Graphical abstract

Coronary artery calcification is an acceptable tool for cardiovascular risk assessment in end-stage renal disease (ESRD) population. We aimed to identify the association and predictive value of components of blood cell parameters with coronary and thoracic aorta vascular calcification (VC) in ESRD population on dialysis. All ESRD patients receiving hemodialysis or peritoneal dialysis aged between 18 and 60 years were included in the study. Exclusion criteria comprised patients with active infection or inflammatory disease, autoimmune disease, congestive heart failure, angina pectoris and/or documented coronary artery disease, thyroid disease, and hepatic dysfunction. Agatston scoring was used for the evaluation of coronary aorta calcification (CAC) score (CACS) and thoracic aorta calcification (TAC) score (TACS). Compared to participants with no VC, those who had VC were statistically significantly older (P

We aimed to validate three IgAN risk models proposed by an international collaborative study and another CKD risk model generated by an extended CKD cohort with our multicenter Chinese IgAN cohort. Biopsy-proven IgAN patients with an eGFR ≥15 ml/min/1.73 m2 at baseline and a minimum follow-up of 6 months were enrolled. The primary outcomes were a composite outcome (50% decline in eGFR or ESRD) and ESRD. The performance of those models was assessed using discrimination, calibration, and reclassification. A total of 2,300 eligible cases were enrolled. Of them, 288 (12.5%) patients reached composite outcome and 214 (9.3%) patients reached ESRD during a median follow-up period of 30 months. Using the composite outcome for analysis, the Clinical, Limited, Full, and CKD models had relatively good performance with similar C statistics (0.81, 0.81, 0.82, and 0.82, respectively). While using ESRD as the end point, the four prediction models had better performance (all C statistics > 0.9). Furthermore, subgroup analysis showed that the models containing clinical and pathological variables (Full model and Limited model) had better discriminatory abilities than the models including only clinical indicators (Clinical model and CKD model) in low-risk patients characterized by higher baseline eGFR (≥60 ml/min/1.73 m2). In conclusion, we validated recently reported IgAN and CKD risk models in our Chinese IgAN cohort. Compared to pure clinical models, adding pathological variables will increase performance in predicting ESRD in low-risk IgAN patients with baseline eGFR ≥60 ml/min/1.73 m2.

Objectives To identify and assess the quality and accuracy of prognostic models for nephropathy and to validate these models in external cohorts of people with type 2 diabetes. Design Systematic review and external validation. Data sources PubMed and Embase. Eligibility criteria Studies describing the development of a model to predict the risk of nephropathy, applicable to people with type 2 diabetes. Methods Screening, data extraction, and risk of bias assessment were done in duplicate. Eligible models were externally validated in the Hoorn Diabetes Care System (DCS) cohort (n=11 450) for the same outcomes for which they were developed. Risks of nephropathy were calculated and compared with observed risk over 2, 5, and 10 years of follow-up. Model performance was assessed based on intercept adjusted calibration and discrimination (Harrell’s C statistic). Results 41 studies included in the systematic review reported 64 models, 46 of which were developed in a population with diabetes and 18 in the general population including diabetes as a predictor. The predicted outcomes included albuminuria, diabetic kidney disease, chronic kidney disease (general population), and end stage renal disease. The reported apparent discrimination of the 46 models varied considerably across the different predicted outcomes, from 0.60 (95% confidence interval 0.56 to 0.64) to 0.99 (not available) for the models developed in a diabetes population and from 0.59 (not available) to 0.96 (0.95 to 0.97) for the models developed in the general population. Calibration was reported in 31 of the 41 studies, and the models were generally well calibrated. 21 of the 64 retrieved models were externally validated in the Hoorn DCS cohort for predicting risk of albuminuria, diabetic kidney disease, and chronic kidney disease, with considerable variation in performance across prediction horizons and models. For all three outcomes, however, at least two models had C statistics >0.8, indicating excellent discrimination. In a secondary external validation in GoDARTS (Genetics of Diabetes Audit and Research in Tayside Scotland), models developed for diabetic kidney disease outperformed those for chronic kidney disease. Models were generally well calibrated across all three prediction horizons. Conclusions This study identified multiple prediction models to predict albuminuria, diabetic kidney disease, chronic kidney disease, and end stage renal disease. In the external validation, discrimination and calibration for albuminuria, diabetic kidney disease, and chronic kidney disease varied considerably across prediction horizons and models. For each outcome, however, specific models showed good discrimination and calibration across the three prediction horizons, with clinically accessible predictors, making them applicable in a clinical setting. Systematic review registration PROSPERO CRD42020192831.

Background Benefits of patients with end‐stage renal disease and atrial fibrillation undergoing peritoneal dialysis (PD) or hemodialysis are unknown. Methods and Results Patients undergoing dialysis were retrieved from Taiwan National Health Insurance Research Database during 2001 to 2013 and separated into PD or hemodialysis. Primary outcomes were ischemic stroke/systemic embolism, major bleeding, and intracranial hemorrhage (ICH). An inverse probability of treatment weighting based on propensity score was used to reduce the confounding. The risk of outcomes between PD and hemodialysis was compared using Cox proportional hazard model for fatal outcomes or Fine and Gray subdistribution hazard model which considered death a competing risk, respectively. A total of 7916 patients with end‐stage renal disease with atrial fibrillation undergoing PD or hemodialysis during 2001 to 2013 were identified. After exclusion criteria, 363 patients receiving PD and 5302 patients receiving hemodialysis were analyzed. At 1‐year follow‐up, the risk of ICH was significantly lower in the PD group compared with the hemodialysis group (0.2% versus 0.9%; subdistribution hazard ratio [SHR], 0.31; 95% CI, 0.17–0.57). At 3‐year follow‐up, the risks of major bleeding and ICH were significantly lower in the PD group compared with the hemodialysis group (major bleeding: 1.8% versus 3.2%; SHR, 0.68; 95% CI, 0.53–0.87; ICH: 0.5% versus 2%; SHR, 0.32; 95% CI, 0.21–0.48). At 5‐year follow‐up, ischemic stroke/systemic embolism, major bleeding, and ICH were significantly lower in the PD group compared with the hemodialysis group (ischemic stroke/systemic embolism: 12.4% versus 17.7%, SHR, 0.87; 95% CI, 0.79–0.96; major bleeding: 2.6% versus 4.1%; SHR, 0.79; 95% CI, 0.64–0.97; ICH: 0.5% versus 2.6%; SHR, 0.25; 95% CI, 0.17–0.37). Conclusions In patients with end‐stage renal disease and atrial fibrillation, dialytic modalities by PD or hemodialysis impacted these patients differently. There were overall reduced ischemic stroke/systemic embolism, major bleeding, and ICH at 5‐year follow‐up in patients undergoing PD compared with hemodialysis.

Introduction Proteomic profiling of end-stage renal disease (ESRD) patients could lead to improved risk prediction and novel insights into cardiovascular disease mechanisms. Plasma levels of 92 cardiovascular disease-associated proteins were assessed by proximity extension assay (Proseek Multiplex CVD-1, Olink Bioscience, Uppsala, Sweden) in a discovery cohort of dialysis patients, the Mapping of Inflammatory Markers in Chronic Kidney disease cohort [MIMICK; n = 183, 55% women, mean age 63 years, 46 cardiovascular deaths during follow-up (mean 43 months)]. Significant results were replicated in the incident and prevalent hemodialysis arm of the Salford Kidney Study [SKS dialysis study, n = 186, 73% women, mean age 62 years, 45 cardiovascular deaths during follow-up (mean 12 months)], and in the CKD5-LD-RTxcohort with assessments of coronary artery calcium (CAC)-score by cardiac computed tomography (n = 89, 37% women, mean age 46 years). Results In age and sex-adjusted Cox regression in MIMICK, 11 plasma proteins were nominally associated with cardiovascular mortality (in order of significance: Kidney injury molecule-1 (KIM-1), Matrix metalloproteinase-7, Tumour necrosis factor receptor 2, Interleukin-6, Matrix metalloproteinase-1, Brain-natriuretic peptide, ST2 protein, Hepatocyte growth factor, TNF-related apoptosis inducing ligand receptor-2, Spondin-1, and Fibroblast growth factor 25). Only plasma KIM-1 was associated with cardiovascular mortality after correction for multiple testing, but also after adjustment for dialysis vintage, cardiovascular risk factors and inflammation (hazard ratio) per standard deviation (SD) increase 1.84, 95% CI 1.26–2.69, p = 0.002. Addition of KIM-1, or nine of the most informative proteins to an established risk-score (modified AROii CVM-score) improved discrimination of cardiovascular mortality risk from C = 0.777 to C = 0.799 and C = 0.823, respectively. In the SKS dialysis study, KIM-1 predicted cardiovascular mortality in age and sex adjusted models (hazard ratio per SD increase 1.45, 95% CI 1.03–2.05, p = 0.034) and higher KIM-1 was associated with higher CACscores in the CKD5-LD-RTx-cohort. Conclusions Our proteomics approach identified plasma KIM-1 as a risk marker for cardiovascular mortality and coronary artery calcification in three independent ESRD-cohorts. The improved risk prediction for cardiovascular mortality by plasma proteomics merit further studies. Electronic supplementary material The online version of this article (10.1007/s40620-018-0556-5) contains supplementary material, which is available to authorized users.

Comorbidity scores to predict mortality are very useful to facilitate decision-making for personalized patient management. This study aim was to assess the contribution of medico-administrative data in addition to French Renal Epidemiology and Information Network (REIN) data to the development of a risk score to predict the 1-year all-cause mortality in patients with End Stage Renal Disease (ESRD), and to compare it with previous scores. Data from a derivation sample (n = 6336 patients who started dialysis in 2015 in France) obtained by linking the REIN and the French National Health Insurance Information System databases were analyzed with multivariate Cox models to select risk factors to establish the score. A randomly chosen validation sample (n = 2716 patients who started dialysis in 2015) was used to validate the score and to compare it with the comorbidity indexes developed by Wright and Charlson. The ability to predict one-year mortality of the score constructed using REIN data linked to the medico-administrative database was not higher than that of the score constructed using only REIN data (i.e., Rennes score). The Rennes score included five comorbidities, albumin, and age. This score (AUC = 0.794, 95%CI: 0.768–0.821) outperformed both the Wright (AUC = 0.631, 95%CI: 0.621–0.639; p

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427–2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862–0.896), AUROC2 = 0.845 (95% CI 0.813–0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients.

Validated tools to improve cardiovascular disease (CVD) risk assessment and mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. Noninvasive measures of arteriosclerosis and subclinical atherosclerosis such as pulse wave velocity (PWV) and carotid intima-media thickness (cIMT), respectively, have emerged as promising risk stratification tools and potential modifiable biomarkers. Their wide use as surrogate markers in clinical research studies is based on the strong pathophysiological links with CVD. However, whether their effect as risk stratification or intervention targets is superior to established clinical approaches is uncertain. In this review, we examine the evidence on the utility of PWV, cIMT, and plaque assessment in routine practice and highlight unanswered questions from the clinician's perspective.Electronic databases PubMed and Google Scholar were searched until February 2020.This narrative review is based on peer-reviewed meta-analyses, national and international societies' guidelines, and on focused critical review of recent original studies and landmark studies in the field.Although patients with CKD are considered in the high-risk CVD groups, there is still need for tools to improve risk stratification and individualized management strategies within this group of patients. Carotid intima-media thickness is associated with all-cause mortality, CVD mortality, and events in CKD and hemodialysis cohorts. However, the evidence that measurement of cIMT has a clinically meaningful role over and above existing risk scores and management strategies is limited. Plaque assessment is a better predictor than cIMT in non-CKD populations and it has been incorporated in recent nonrenal-specific guidelines. In the CKD population, one large observational study provided evidence for a potential role of plaque assessment in CKD similar to the non-CKD studies; however, whether it improves prediction and outcomes in CKD is largely understudied. Pulse wave velocity as a marker of arterial stiffness has a strong pathophysiological link with CVD in CKD and numerous observational studies demonstrated associations with increased cardiovascular risk. However, PWV did not improve CVD reclassification of dialysis patients when added to common risk factors in a reanalysis of ESRD cohorts with available PWV data. Therapeutic strategies to regress PWV, independently from blood pressure reduction, have not been studied in well-conducted randomized trials.This study provides a comprehensive review based on extensive literature search and critical appraisal of included studies. Nevertheless, formal systematic literature review and quality assessment were not performed and the possibility of selection bias cannot be excluded.Larger, prospective, randomized studies with homogeneous approach, designed to answer specific clinical questions and taking into consideration special characteristics of CKD and dialysis, are needed to study the potentially beneficial role of cIMT/plaque assessment and PWV in routine practice.Les outils validés pour faciliter l’évaluation des risques de maladies cardiovasculaires (MCV) et de mortalité chez les patients atteints d’insuffisance rénale terminale (IRT) sont insuffisants. Les mesures non invasives de l’artériosclérose et de l’artériosclérose infraclinique, respectivement la vitesse de l’onde de pouls (VOP) et la mesure de l’épaisseur intima-média de la carotide (EIMc), sont apparues comme des outils prometteurs de stratification des risques et des biomarqueurs potentiellement modifiables. L’usage répandu de la VOP et de l’EIMc comme marqueurs de substitution dans les études cliniques est fondé sur leurs liens physiopathologiques étroits avec les MCV. On ignore toutefois si leur effet pour la stratification des risques ou comme cibles d’intervention est supérieur aux approches cliniques établies. Cette revue examine les données probantes sur la pertinence des mesures de VOP et d’EIMc et de l’analyse plaquettaire dans les pratiques courantes et met en lumière les questions sans réponses du point de vue du clinicien.Les bases de données PubMed et Google Scholar ont été consultées jusqu’en février 2020.Cette revue narrative est fondée sur des méta-analyses révisées par les pairs, sur les lignes directrices de sociétés nationales et internationales et sur un examen critique et ciblé des études originales récentes et d’études phares dans le domaine.Bien que les patients atteints d’IRT fassent déjà partie des groupes présentant un risque élevé de MCV, l’ajout d’outils pour améliorer la stratification des risques et de stratégies de gestion individualisées est toujours nécessaire pour ce groupe de patients. L’EIMc est associée à la mortalité toutes causes, ainsi qu’aux risques d’événements cardiovasculaires et de mortalité liée aux MCV dans les cohortes de patients atteints d’IRT et hémodialysés. Les preuves soutenant un rôle cliniquement significatif de la mesure de l’EMIc au-delà des scores de risque et des stratégies de gestion existantes sont toutefois limitées. L’analyse plaquettaire s’avère un meilleur prédicteur que l’EIMc dans les populations non atteintes d’IRT et a récemment été intégrée aux lignes directrices non liées aux maladies rénales. Dans les populations atteintes d’IRT, une vaste étude observationnelle a fourni des preuves quant à un possible rôle de l’analyse plaquettaire similaire à celui rapporté dans les études ne portant pas sur des patients atteints d’IRT. Cependant, la question de savoir si cette mesure améliore la prédiction et les résultats des patients atteints d’IRT demeure largement sous-étudiée. La VOP, à titre de marqueur de la rigidité artérielle, a un lien physiopathologique fort avec les MCV en contexte d’IRT, plusieurs études observationnelles ayant démontré des associations avec un risque accru d’événements cardiovasculaires. Par contre, la VOP n’a pas amélioré le reclassement cardiovasculaire des patients dialysés lorsqu’on l’a ajoutée aux facteurs de risques communs dans une nouvelle analyse des cohortes de patients atteints d’IRT disposant de données de VOP. Les stratégies thérapeutiques pour réduire la VOP, indépendamment de la pression artérielle, n’ont pas été étudiées dans le cadre d’essais à répartition aléatoire bien menés.Cette étude fournit une revue complète fondée sur une recherche documentaire approfondie et une évaluation critique des études incluses. Cependant, aucune analyse documentaire systématique formelle ou d’évaluation de la qualité n’ont été effectuées et un biais de sélection ne peut être exclu.L’étude d’un rôle potentiellement bénéfique des mesures de VOP et d’EIMc et de l’analyse plaquettaire dans la pratique courante en contexte d’IRT requiert des essais prospectifs de grande envergure avec répartition aléatoire. Ces essais devraient s’articuler autour d’une approche homogène, être conçus pour répondre à des questions cliniques spécifiques et tenir compte des caractéristiques propres aux patients atteints d’IRT et dialysés.

Background The Kidney Failure Risk Equation (KFRE) uses the 4 variables of age, sex, urine albumin-to-creatinine ratio (ACR), and estimated glomerular filtration rate (eGFR) in individuals with chronic kidney disease (CKD) to predict the risk of end stage renal disease (ESRD), i.e., the need for dialysis or a kidney transplant, within 2 and 5 years. Currently, national guideline writers in the UK and other countries are evaluating the role of the KFRE in renal referrals from primary care to secondary care, but the KFRE has had limited external validation in primary care. The study’s objectives were therefore to externally validate the KFRE’s prediction of ESRD events in primary care, perform model recalibration if necessary, and assess its projected impact on referral rates to secondary care renal services. Methods and findings Individuals with 2 or more Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFR values < 60 ml/min/1.73 m2 more than 90 days apart and a urine ACR or protein-to-creatinine ratio measurement between 1 December 2004 and 1 November 2016 were included in the cohort. The cohort included 35,539 (5.6%) individuals (57.5% female, mean age 75.9 years, median CKD-EPI eGFR 51 ml/min/1.73 m2, median ACR 3.2 mg/mmol) from a total adult practice population of 630,504. Overall, 176 (0.50%) and 429 (1.21%) ESRD events occurred within 2 and 5 years, respectively. Median length of follow-up was 4.7 years (IQR 2.8 to 6.6). Model discrimination was excellent for both 2-year (C-statistic 0.932, 95% CI 0.909 to 0.954) and 5-year (C-statistic 0.924, 95% 0.909 to 0.938) ESRD prediction. The KFRE overpredicted risk in lower (, In this cohort study, Rupert Major and colleagues evaluate the performance of the Kidney Failure Risk Equation in chronic kidney disease patients in primary care settings and project impact of a recalibrated equation on referral practices and patient outcomes., Author summary Why was this study done? The Kidney Failure Risk Equation (KFRE) has been developed in multinational chronic kidney disease (CKD) cohorts to predict end stage renal disease (ESRD) events (the need for dialysis or a kidney transplant) over 2- and 5-year time periods. The performance of the KFRE has not been extensively tested in UK and European primary care CKD populations. The projected impact of the KFRE on referrals from primary to secondary care has not been studied, and it is unclear what criteria for referrals should be used. What did the researchers do and find? Our study suggests that the KFRE has largely accurate performance (discrimination) for predicting ESRD, but requires adjustment (recalibration) for a primary care setting. Compared to current referral criteria, using hybrid criteria of a ≥5% risk of ESRD over 5 years from the recalibrated KFRE and/or a urine albumin-to-creatinine ratio (ACR) of ≥70 mg/mmol would reduce the number of individuals eligible for referral without increasing the number who later develop ESRD and are not initially eligible for referral. What do these findings mean? The recalibrated KFRE can be used to predict the risk of ESRD over 2 and 5 years in primary care CKD. The KFRE, in conjunction with the ACR criterion, can be used to triage CKD referrals from primary to secondary care.

In patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) and renal involvement, the development of end-stage renal disease (ESRD) remains an undesired issue. To date, reported predictors of renal outcome are mainly patients’ age, severe renal dysfunction and histopathological findings at presentation.1 2 Histopathological classification as defined by Berden et al was proposed to be helpful with the highest renal survival rates in the focal group and the poorest in the sclerotic group.3 4 Recently, Brix et al suggested the antineutrophil cytoplasmic antibody renal risk score (ARRS) to predict ESRD in patients with AAV.5 Unlike Berden's classification, ARRS combines histopathological findings (the percentage of normal glomeruli, tubular atrophy and interstitial fibrosis) with baseline glomerular filtration rate (GFR). Here, we aimed to assess the prognostic factors for renal survival and to evaluate the performances of Berden’s histopathological classification and ARRS for predicting ESRD. We reviewed the medical records of all patients diagnosed …

BACKGROUND AND OBJECTIVES: Uromodulin is exclusively produced by tubular epithelial cells and released into urine and serum. Higher serum uromodulin has been associated with lower risk for kidney failure in Chinese patients with CKD and with lower risk for mortality in the elderly and in patients undergoing coronary angiography. We hypothesized that lower serum uromodulin is associated with mortality, cardiovascular events, and kidney failure in white patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We measured serum uromodulin in 5143 participants enrolled in the German CKD (GCKD) study. The associations of baseline serum uromodulin with all-cause mortality, major adverse cardiovascular events (MACE; a composite of cardiovascular mortality, nonfatal myocardial infarction or stroke, or incident peripheral vascular disease), and kidney failure (dialysis or transplantation) were evaluated using multivariable Cox proportional hazard regression analyses in a cohort study design, adjusting for demographics, eGFR, albuminuria, cardiovascular risk factors, and medication. RESULTS: The mean age of participants was 60±12 years, 60% were male. Mean serum uromodulin concentration was 98±60 ng/ml, eGFR was 49±18 ml/min per 1.73 m(2), and 78% had eGFR

Background and objectives Elevated BP load is part of the criteria for ambulatory hypertension in pediatric but not adult guidelines. Our objectives were to determine the prevalence of isolated BP load elevation and associated risk with adverse outcomes in children with CKD, and to ascertain whether BP load offers risk discrimination independently or in conjunction with mean ambulatory BPs. Design, setting, participants, & measurements We studied 533 children in the CKD in Children (CKiD) Study to determine the prevalence of normotension, isolated BP load elevation (≥25% of all readings elevated but mean BP normal), and ambulatory hypertension. We examined the association between these categories of BP control and adverse outcomes (left ventricular hypertrophy [LVH] or ESKD). We used c-statistics to determine risk discrimination for outcomes by BP load used either independently or in conjunction with other BP parameters. Results Overall, 23% of the cohort had isolated BP load elevation, but isolated BP load elevation was not statistically significantly associated with LVH in cross-section (odds ratio, 1.8; 95% CI, 0.8 to 4.2) or time to ESKD (hazard ratio, 1.2; 95% CI, 0.7 to 2.0). In unadjusted cross-sectional analysis, every 10% higher systolic BP load was associated with 1.1-times higher odds of LVH (95% CI, 1.0 to 1.3), but discrimination for LVH was poor (c=0.61). In unadjusted longitudinal analysis, every 10% higher systolic BP load was associated with a 1.2-times higher risk of ESKD (95% CI, 1.1 to 1.2), but discrimination for ESKD was also poor (c=0.60). After accounting for mean systolic BP, systolic BP load was not statistically significantly associated with either LVH or ESKD. Findings were similar with diastolic BP load. Conclusions BP load does not provide additive value in discriminating outcomes when used independently or in conjunction with mean systolic BP in children with CKD. Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_03_11_CPOD10130819.mp3

Background and aims IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide and a leading cause of end stage renal disease (ESRD). In addition to classical progression factors, other atherosclerosis-related factors, including hyperuricemia (HU), have been associated to the renal progression of IgAN. Increased serum uric acid (SUA) levels are well known to be concomitant of cardiovascular and kidney diseases, and have been proposed to be implicated in the development of arteriolar damage (AD). The aim of the present study was to explore the correlation between SUA levels, renal damage and its implication for outcome in IgAN patients. Methods and results Clinical, laboratory and histologic data of 145 patients with biopsy proven IgAN were collected and retrospectively analyzed to determine the correlation between SUA levels, renal damage and the primary outcome (death or ESRD). Biopsy-proven AD was defined by the presence of arteriolar hyalinosis and/or intimal thickening. HU, defined as the highest SUA gender-specific tertile, was >7.7 mg/dl for males and >6.2 mg/dl for females. The prevalence of AD increased with the increase in the SUA level tertiles (p = 0.02). At logistic regression analysis SUA was independently related to the presence of AD (OR 1.75 [95%CI 1.10–2.93], p = 0.03). HU and AD had a synergic impact on progression of IgAN. Patients having both AD and HU, showed a reduced survival free from the primary outcome as compared to those having only one risk factor or neither (p = 0.01). Conclusions SUA levels are independently associated with AD and poor prognosis in patients with IgAN.

ObjectiveTo examine the relative risk of end-stage renal disease (ESRD) requiring dialysis among treated ankylosing spondylitis (AS) patients compared with non-AS individuals.MethodsWe used claims data from Taiwan's National Health Insurance Research Database obtained between 2003 and 2012, and enrolled 37,070 newly treated AS patients and randomly selected 370,700 non-AS individuals matched (1:10) for age, sex and year of index date. Those with a history of chronic renal failure or dialysis were excluded. After adjusting for age, sex, diabetes mellitus, hypertension, IgA nephropathy, frequency of serum creatinine examinations, use of methotrexate, sulfasalazine, ciclosporis, corticosteroid, aminoglycoside, amphotericin B, cisplatin, contrast agents and annual cumulative defined daily dose (cDDD) of traditional NSAIDs, selective cyclooxygenase-2 inhibitors (COX-2i) and preferential COX-2i, we calculated the adjusted hazard ratios (aHRs) with 95% confidence intervals using the Cox proportional hazard model to quantify the risk of ESRD in AS patients. We re-selected 6621 AS patients and 6621 non-AS subjects by further matching (1:1) for cDDDs of three groups of NSAIDs to re-estimate the aHRs for ESRD.ResultsFifty-one (0.14%) of the 37,070 AS patients and 1417 (0.38%) of the non-AS individuals developed ESRD after a follow-up of 158,846 and 1,707,757 person-years, respectively. The aHR for ESRD was 0.59 (0.42-0.81) in AS patients compared with non-AS individuals. However, after further matching for cDDD of NSAIDs, the aHR of ESRD was 1.02 (0.41-2.53). Significant risk factors included hypertension, IgA nephropathy and use of COX-2i.ConclusionsThe risk of ESRD was not significantly different between treated AS patients and non-AS individuals matched for age, sex, year of index date and dose of NSAID.

Background Chronic kidney disease (CKD) is an independent risk factor for stroke in the general population. The impact of prior stroke on major clinical outcomes in CKD populations is poorly characterised. Methods The Salford Kidney Study is a UK prospective cohort of more than 3000 patients recruited since 2002 and followed until March 2018. Multivariable Cox regression examined associations of stroke at two time points; cohort inception, and at dialysis initiation, with risks of death, non-fatal cardiovascular events (NFCVE) and end stage renal disease (ESRD). Results 277 (9.1%) of 3060 patients suffered a prior stroke and this was associated with mortality, ESRD and future NFCVE after cardiovascular risk factor adjustments. Median survival for prior stroke patients was 40 months vs 77 months in patients without a stroke. Prior stroke was independently associated with mortality (HR 1.20 95%CI 1.0–1.43, p = 0.05). Of 579 patients who reached ESRD and commenced dialysis, a prior stroke (N = 48) was independently associated with mortality. Median survival for the prior stroke group was 29 months compared with 50 months for the non-stroke group. Only 70 and 75% of patients who had suffered an ischaemic stroke were prescribed antiplatelets or statins respectively. Conclusions A diagnosis of stroke is strongly and independently associated with several adverse clinical outcomes for patients with CKD. Prior stroke profoundly alters cardiovascular risk in CKD patients. Greater attention to primary and secondary preventive strategies is warranted which may improve these outcomes.

Cancer is a global issue in recent decade. Despite this alarming increase in the incidence of cancer, to date, whether the risk of developing cancer differs among peritoneal dialysis (PD) and hemodialysis (HD) patients is still uncertain. In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan, which provides coverage to almost 99% of the nation's population. After matching, a total of 4491 (or 3369) incident PD patients and 8982 (or 6738) incident HD patients between 2000 and 2009 were enrolled from the database. In addition, 22,455 (or 16,845) nondialysis patients were selected as a control group. The patients were monitored for the occurrence of cancer until 2010, and their data were analyzed using several different models. In general, the results showed that the risks of hepatocellular, kidney, bladder, extra kidney/bladder urinary tract, and thyroid cancers were higher in dialysis patients. We also compared the risk of cancer between two dialysis groups by using the HD patients as the reference group. The result showed that there is no significant different for each cancer risk between two dialysis groups. In conclusion, dialysis patients had a higher risk of certain types of cancer than those in the nonuremia group. However, there was no significant difference in the cancer risk between the two dialysis groups when compared directly.

Background Mortality in end stage renal disease (ESRD) is higher than many malignancies. There is no data about the optimal way to present information about projected survival to patients with ESRD. In other areas, graphs have been shown to be more easily understood than narrative. We examined patient comprehension and perspectives on graphs in communicating projected survival in chronic kidney disease (CKD). Methods One hundred seventy-seven patients with CKD were shown 4 different graphs presenting post transplantation survival data. Patients were asked to interpret a Kaplan Meier curve, pie chart, histogram and pictograph and answer a multi-choice question to determine understanding. Results We measured interpretation, usefulness and preference for the graphs. Most patients correctly interpreted the graphs. There was asignificant difference in the percentage of correct answers when comparing different graph types (p = 0.0439). The pictograph was correctly interpreted by 81% of participants, the histogram by 79%, pie chart by 77% and Kaplan Meier by 69%. Correct interpretation of the histogram was associated with educational level (p = 0.008) and inversely associated with age > 65 (p = 0.008). Of those who interpreted all four graphs correctly, there was an association with employment (p = 0.001) and New Zealand European ethnicity (p = 0.002). 87% of patients found the graphs useful. The pie chart was the most preferred graph (p 0.002). The readability of the graphs may have been improved with an alternative colour choice, especially in the setting of visual impairment. Conclusion Visual aids, can be beneficial adjuncts to discussing survival in CKD.

Background Patient engagement in end-stage renal disease (ESRD) is expected to result in a more patient-centered approach to care that aligns with patients’ values, preferences, and goals for treatment. Nevertheless, no previous studies of which we are aware have evaluated patients’ benefit-risk preferences for the management of anemia associated with ESRD. The primary objective of this study was to quantify the tradeoffs patients are willing to make between cardiovascular risks associated with some anemia medicines and red blood cell (RBC) transfusions. A secondary objective was to quantify the importance of avoiding transfusion-related risks. Methods A survey instrument was developed from the clinical literature, clinician input, patient-education resources, and a patient focus group. The survey instrument was qualitatively pretested before its administration to a broader sample of patients. The National Kidney Foundation invited individuals in the United States to participate in the survey. In a discrete-choice experiment (DCE), respondents chose between two hypothetical anemia medications in a series of questions. Each medication was defined by symptom relief, frequency of transfusions, cardiovascular risk, mode of administration, and out-of-pocket cost. The survey also included a best-worst scaling (BWS) exercise to quantify the importance of avoiding attributes of blood transfusions. Results from the DCE were used to estimate relative importance and marginal willingness to pay. Results from the BWS were converted to relative importance weights. Results A total of 200 individuals completed the survey. Patients were willing to accept a 6% medication-related risk of heart attack to avoid having two RBC transfusions per month. Symptom relief and mode of administration were of moderate importance. The most important transfusion-related risk to avoid was transfusion-related lung injury. Conclusions Patients with ESRD and anemia have measurable treatment preferences and are willing to accept risks associated with anemia medications to avoid transfusions. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0664-9) contains supplementary material, which is available to authorized users.

Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease (ESRD). The development and progression of nephropathy is strongly determined by genetic factors, and few genes have been shown to contribute to DN. An insertion/deletion (I/D) polymorphism of the gene encoding angiotensin-converting enzyme (ACE) was reported as a candidate gene predisposing to DN and ESRD. Accordingly, we investigated the frequency of ACE I/D polymorphism in 50 patients with DN, of whom 33 had ESRD and compared them with 64 patients with type 2 diabetes mellitus (T2DM) but with normal renal function. Polymerase chain reaction amplification, using specific primers, was performed to genotype ACE I/D. Chi-square test was used to assess the differences between the groups. The frequencies of the ACE genotypes were as follows: 48% D/D, 40% I/D, and 12% I/I in patients with DN in contrast to 32.8% D/D, 45.3% I/D, and 21.9% I/I in T2DM. The distribution of the D/D, D/I, and I/I genotypes did not significantly differ between T2DM and DN. However, having the D allele carried a risk for the development of DN [odds ratio (OD), 1.71, P = 0.054]. On the other hand, the distribution of the D/D, D/I, and I/I genotypes was significantly different between T2DM and ESRD patients, χ2 = 7.23, P = 0.027. This was reflected by the D allele which carried a risk for the development of ESRD (OR, 2.51, P = 0.0057). These findings suggest that the D allele may be considered as a risk factor for both the development of DN and the progression of DN to ESRD in Lebanese population with T2DM.

Aims Despite several studies reporting similar outcomes for peritoneal dialysis (PD) and hemodialysis (HD), the former is underused worldwide, with a PD prevalence of 15% in Italy. In 2008, the Unit of Nephrology and Dialysis of the Healthcare Trust of the Autonomous Province of Trento implemented a successful PD program which has increased the proportion of PD incident patients from 7 to 47%. We aimed to assess the effect of this extensive use of PD by comparing HD and PD in terms of survival and time-to-transplantation. Methods A total of 334 HD and 153 PD incident patients were enrolled between January 2008 and December 2014. After screening for exclusion criteria and propensity score matching, 279 HD and 132 PD patients were analyzed. Survival and time-to-transplantation were assessed by competing-risks regression models, using death and transplantation as primary and competing events. Results Crude and adjusted regression models for survival revealed the absence of significant differences between HD and PD cumulative incidence functions (subhazard ratio: 1.09, p = 0.62 and 1.34, p = 0.10, respectively). Differently, crude and adjusted regression models for transplantation revealed a lower time-to-transplantation for PD versus HD patients (subhazard ratio: 2.34, p

STUDY OBJECTIVES: Peritoneal dialysis (PD) is a renal replacement therapy. One concern is whether patients on PD have a higher risk of sleep apnea (SA) due to intra-abdominal pressure increase and worsened ultrafiltration capacity. Despite this concern, to date, whether the risk of SA differs between PD, hemodialysis (HD), and groups without uremia is still uncertain. METHODS: In this retrospective cohort study, data were obtained from the National Health Insurance Research Database of Taiwan. This database enrolled almost all patients on dialysis in the country. A total of 7,645 incident patients on PD and 38,225 incident patients on HD were enrolled. In addition, 38,225 patients without uremia were selected as the comparison cohort. Individuals were monitored for the occurrence of SA until 2013. RESULTS: The results showed that patients on PD, regardless of sex, all had a higher risk of SA than non-dialysis groups. In contrast, the risk of SA in patients on HD was not significantly different from that of patients without uremia. We also compared the risk of SA between patients on PD and HD directly. The results showed that male patients on PD had a significantly higher risk of SA risk than male patients on HD. However, the risk of SA did not differ between female patients on PD and HD. CONCLUSIONS: Patients on PD should receive regular SA assessments and that an increased awareness and a higher index of suspicion for SA should be maintained in these patients, especially male patients. CITATION: Lee YC, Hung SY, Wang HK, Lin CW, Wang HH, Chang MY, Wu CF, Sung JM, Chiou YY, Lin SH. Male patients on peritoneal dialysis have a higher risk of sleep apnea. J Clin Sleep Med. 2019;15(7):937–945.

A valid diet quality assessment scale has not been investigated in hemodialysis patients. We aimed to adapt and validate the alternative healthy eating index in hemodialysis patients (AHEI-HD), and investigate its associations with all-cause mortality. A prospective study was conducted on 370 hemodialysis patients from seven hospital-based dialysis centers. Dietary data (using three independent 24-hour dietary records), clinical and laboratory parameters were collected. The construct and criterion validity of original AHEI-2010 with 11 items and the AHEI-HD with 16 items were examined. Both scales showed reasonable item-scale correlations and satisfactory discriminant validity. The AHEI-HD demonstrated a weaker correlation with energy intake compared with AHEI-2010. Principle component analysis yielded the plateau scree plot line in AHEI-HD but not in AHEI-2010. In comparison with patients in lowest diet quality (tertile 1), those in highest diet quality (tertile 3) had significantly lower risk for death, with a hazard ratio (HR) and 95% confidence intervals (95%CI) of HR: 0.40, 95%CI: 0.18 &ndash, 0.90, p = 0.028, as measured by AHEI-2010, and HR: 0.37, 95%CI: 0.17&ndash, 0.82, p = 0.014 as measured by AHEI-HD, respectively. In conclusion, AHEI-HD was shown to have greater advantages than AHEI-2010. AHEI-HD was suggested for assessments of diet quality in hemodialysis patients.

Background Whole-exome sequencing (WES) finds a CKD-related mutation in approximately 20% of patients presenting with CKD before 25 years of age. Although provision of a molecular diagnosis could have important implications for clinical management, evidence is lacking on the diagnostic yield and clinical utility of WES for pediatric renal transplant recipients. Methods To determine the diagnostic yield of WES in pediatric kidney transplant recipients, we recruited 104 patients who had received a transplant at Boston Children’s Hospital from 2007 through 2017, performed WES, and analyzed results for likely deleterious variants in approximately 400 genes known to cause CKD. Results By WES, we identified a genetic cause of CKD in 34 out of 104 (32.7%) transplant recipients. The likelihood of detecting a molecular genetic diagnosis was highest for patients with urinary stone disease (three out of three individuals), followed by renal cystic ciliopathies (seven out of nine individuals), steroid-resistant nephrotic syndrome (nine out of 21 individuals), congenital anomalies of the kidney and urinary tract (ten out of 55 individuals), and chronic glomerulonephritis (one out of seven individuals). WES also yielded a molecular diagnosis for four out of nine individuals with ESRD of unknown etiology. The WES-related molecular genetic diagnosis had implications for clinical care for five patients. Conclusions Nearly one third of pediatric renal transplant recipients had a genetic cause of their kidney disease identified by WES. Knowledge of this genetic information can help guide management of both transplant patients and potential living related donors.

Aims To systematically review literature comparing bare metal stent (BMS) to drug-eluting stent (DES) in end-stage renal disease (ESRD) patients on dialysis. ESRD patients on dialysis often suffer from accelerated atherosclerosis and higher rate of stent-related complications including major adverse cardiovascular events. Because dialysis usually qualifies ineligibility for randomized clinical trials, an evidenced-based stent choice for these patients is scarce. Methods PUBMED, CINHAL, COCHRANE, EMBASE and WEB OF SCIENCE were searched for studies comparing BMS vs. DES outcome in ESRD patients on dialysis. Results Twenty studies including 64 232 patients were considered. The use of DES was significantly associated with a reduction in all-cause mortality [odds ratio (OR) 0.83, 95% confidence interval (CI) 0.76-0.89], death from a cardiovascular cause (OR 0.80, 95% CI 0.76-0.84) and target lesion revascularization/target vessel revascularization (OR 0.73, 95% CI 0.53-1.00). No significant difference was found in stent thrombosis (OR 1.08, 95% CI 0.50-2.33) and myocardial infarction incidence (OR 0.91, 95% CI 0.69-1.20). Conclusions Our meta-analysis shows a significant reduction in all-cause and cardiovascular mortality with the use of DES over BMS in dialyzed patients. Despite the lack of randomized studies, systematic use of DES in these high-risk patients should thus reasonably be considered as a first option in percutaneous coronary intervention candidates.

Background End-stage renal disease frequently leads to increased cardiovascular mortality. Cardiovascular autonomic neuropathy (CAN) may be predictive of cardiac arrhythmias and sudden cardiac death in patients with end-stage renal disease. Methods A total of 70 patients with end-stage renal disease were included in the study. The assessment of cardiac dysautonomia was based on the four standardized tests performed at the baseline and, again, at the end of the study. The criteria for CAN included at least two abnormal test results. Results Fifty of 70 patients completed the study and were followed-up after one year. Out of the 50 patients, 44 (88%) had CAN at baseline. Twelve (24%) patients died at the one-year follow-up. Sudden cardiac death was reported in seven out of 12 (58%) patients. All seven patients who died had high dysautonomia scores (three abnormal tests) at the baseline. There was a significantly higher percentage of patients with all four abnormal tests amongst patients who died of any cause (56% vs. 17%; RR 6.07, 95% CI 1.29-28.49; p-value 0.02) or due to sudden cardiac death (43% vs. 10.5%; RR 6.37, 95% CI 1.03-39.36; p-value 0.04). All five patients who did not have CAN at the baseline developed this abnormality on repeat testing after one year. Conclusion The prevalence of CAN in patients with end-stage renal disease on maintenance hemodialysis was significantly higher. CAN was an independent predictor of all-cause and cardiovascular mortality, which highlights it as a risk stratification tool in patients with end-stage renal disease.

Women with hypertensive pregnancy complications are at greater risk of developing cardiovascular disease (CVD), metabolic diseases, stroke, and end-stage renal disease (ESRD) later in life. Pregnancy complications affect not only the mother’s long-term health but also the health of the fetus immediately after delivery and into adulthood. The health of the fetus until adulthood can be influenced by developmental programming, in which the fetus is exposed to insults that will ultimately affect the growth of the offspring and increase the offspring’s risk of developing hypertension, coronary heart disease, metabolic disease, and chronic kidney disease in adulthood. Preeclampsia, the onset of hypertension during pregnancy, is one of the major risk factors for the development of renal disease, cerebral disease, and CVD in the mother. Women with preeclampsia are at a 5–12-fold increased risk of developing ESRD, 2-fold increased risk of stroke, and 2-fold increased risk of developing CVD later in life. In this review article, we discuss 1) preeclampsia, 2) the risk of developing CVD, renal disease, or stroke later in life for women with hypertensive pregnancies, and 3) the effects of a hypertensive pregnancy on the offspring.

BACKGROUND Patients with chronic kidney disease (CKD) are at an increased risk of developing end-stage renal disease (ESRD). We assessed for the first time whether urinary free light chains (FLC) are independently associated with risk of ESRD in patients with CKD, and whether they offer incremental value in risk stratification. MATERIALS AND METHODS We measured urinary FLCs in 556 patients with CKD from a prospective cohort study. The association between urinary kappa/creatinine (KCR) and lambda/creatinine (LCR) ratios and development of ESRD was assessed by competing-risks regression (to account for the competing risk of death). The change in C-statistic and integrated discrimination improvement were used to assess the incremental value of adding KCR or LCR to the Kidney Failure Risk Equation (KFRE). RESULTS 136 participants developed ESRD during a median follow-up time of 51 months. Significant associations between KCR and LCR and risk of ESRD became non-significant after adjustment for estimated glomerular filtration rate (eGFR) and albumin/creatinine ratio (ACR), although having a KCR or LCR >75th centile remained independently associated with risk of ESRD. Neither KCR nor LCR as continuous or categorical variables provided incremental value when added to the KFRE for estimating risk of ESRD at two years. CONCLUSIONS Urinary FLCs have an association with progression to ESRD in patients with CKD which appears to be explained to a degree by their correlation with eGFR and ACR. Levels above the 75th centile do have an independent association with ESRD, but do not improve upon a current model for risk stratification.

Survival in the pediatric end-stage renal disease (ESRD) population has improved substantially over recent decades. Nonetheless, mortality remains at least 30 times higher than that of healthy peers. Patient survival is multifactorial and dependent on various patient and treatment characteristics and degree of economic welfare of the country in which a patient is treated. In this educational review, we aim to delineate current evidence regarding mortality risk in the pediatric ESRD population and provide pediatric nephrologists with up-to-date information required to counsel affected families.

Background: The risk of cardiovascular mortality is high among adults with end-stage renal disease (ESRD) undergoing hemodialysis. Waist-to-hip ratio (WHR), a metric of abdominal adiposity, is a predictor of cardiovascular disease (CVD) and mortality in the general population; however, no studies have examined the association with CVD mortality, particularly sudden cardiac death (SCD), in incident hemodialysis. Methods: Among 379 participants incident (< 6 months) to hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD study, we evaluated associations between WHR and risk of CVD mortality, SCD, and non-CVD mortality in Cox proportional hazards regression models. Results: At study enrollment, mean age was 55 years with 41% females, 73% African Americans, and 57% diabetics. Mean body mass index was 29.3 kg/m2, and mean WHR was 0.95. During a median follow-up time of 2.5 years, there were 35 CVD deaths, 15 SCDs, and 48 non-CVD deaths. Every 0.1 increase in WHR was associated with higher risk (hazard ratio [95% CI]) of CVD mortality (1.75 [1.06–2.86]) and SCD (2.45 [1.20–5.02]), but not non-CVD mortality (0.93 [0.59–1.45]), independently of demographics, body mass index, comorbidities, inflammation, and traditional CVD risk factors. Conclusions: WHR is significantly associated with CVD mortality including SCD, independently of other CVD risk factors in incident hemodialysis. This simple, easily obtained bedside metric may be useful in dialysis patients for CVD risk stratification.

Obesity is on the rise and the number of end stage renal disease patients who are obese parallel this trend. There is no universally accepted guideline for wait-listing end stage renal disease obese patients in order to reduce short-term complications and improve long-term survival of the kidney graft. Criteria for acceptance are variable among transplant centres, as do post-transplant policies. Careful risk assessment to maximise the benefits of the limited organ donor resource must be undertaken prior to wait-list an obese kidney transplant candidate. Likewise, close post transplantation follow-up for this higher risk group should be implemented as per the general population, but the body mass index per se should not be a barrier to get access to transplantation.

Importance The kidney failure risk equation (KFRE) has been shown to accurately estimate progression to kidney failure in adults with chronic kidney disease (CKD). Use of the KFRE in children with CKD, if accurate, would help to optimize planning for end-stage renal disease (ESRD) care. Objective To determine whether the KFRE adequately discriminates the risk of ESRD in children with CKD. Design, Setting, and Participants This retrospective cohort study included 603 children with an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2in the Chronic Kidney Disease in Children study, a national multicenter observational study. Data were collected from January 1, 2005, through July 31, 2013, and analyzed from September 30, 2016, through September 8, 2017. Exposures The primary predictive factors were the 4-variable (age, sex, bedside Schwartz estimated glomerular filtration rate, and ratio of albumin to creatinine levels) and 8-variable (4 variables plus serum calcium, phosphate, bicarbonate, and albumin levels) KFREs, which provide 1-, 2-, and 5-year estimates of the risk of progression to ESRD. Main Outcomes and Measures Time to ESRD. The Cox proportional hazards model was used to examine the association between the KFRE score and time to ESRD. C statistics were used to discriminate ESRD risk by the KFRE, with a value of greater than 0.80 indicating strong discrimination. Results Of the 603 children included in the study, 378 were boys (62.7%) and 225 were girls (37.3%); median age at study entry was 12 years (interquartile range, 8-15 years). Median estimated glomerular filtration rate was 44 mL/min/1.73 m2. Four hundred fifty-seven participants (75.8%) had a nonglomerular cause of CKD. Median observation time was 3.8 years (interquartile range, 1.7-6.2 years); 144 (23.9%) developed ESRD within 5 years of enrollment. The 4-variable KFRE scores discriminated risk of ESRD, with C statistics of 0.90, 0.86, and 0.81 for the 1-, 2-, and 5-year risk scores, respectively. Results were similar using the 8-variable equation. Conclusions and Relevance The KFRE is a simple tool that provides excellent discrimination of the risk of ESRD. Results suggest that the KFRE could be incorporated into the clinical care of children with CKD to aid in anticipatory guidance, timing of referral for transplant evaluation, and planning for dialysis access.

PURPOSE OF REVIEW Living kidney donation improves the lives of those with kidney failure, but there are potential risks to the donor. We review two recent publications that describe the long-term risk of end-stage renal disease (ESRD) in living kidney donors. RECENT FINDINGS One study reported that the long-term risk (median follow-up 15.1 years) of ESRD was, in relative terms, 11-fold higher in living kidney donors compared to healthy nondonors, and suggested a hereditary association since all affected donors were biologically related to their recipients and the causes were predominantly immunological diseases. In a second study, we estimated that the long-term risk (median follow-up 7.6 years) of ESRD was, in relative terms, eight-fold higher in living kidney donors compared to healthy matched nondonors. In both studies, the absolute increase in the 15-year incidence of ESRD from donation was below 0.5%. There are limitations in these studies, which have raised questions about the accuracy of the estimates of risk. SUMMARY The results of these studies should be discussed with potential living kidney donors with an emphasis on the low 15-year incidence of ESRD following donation. The lifetime incidence of ESRD for donors of different age, race, and other characteristics requires further study.

BACKGROUND AND OBJECTIVES: Kidney length is often measured during routine abdominal ultrasonography and may be of use to identify patients at high vascular and renal risk. We aimed to explore patient characteristics related to kidney length, from which reference values were derived, and evaluate the relationship between kidney length and the risk of cardiovascular events and ESRD in high-risk patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study population consisted of 10,251 patients with clinical manifest arterial disease or vascular risk factors included in the Second Manifestations of ARTerial disease (SMART) Study cohort between 1996 and 2014. Linear regression was used to explore patient characteristics of kidney length. The relationship between kidney length and cardiovascular events (myocardial infarction, stroke, and cardiovascular mortality), all-cause mortality, and ESRD was analyzed using Cox regression. Kidney length was analyzed in tertiles, using the second tertile as the reference category. RESULTS: Kidney length was strongly correlated with body surface area (2.04 mm; 95% confidence interval [95% CI], 1.95 to 2.13 per 0.1 m(2) increase) and eGFR (1.62 mm; 95% CI, 1.52 to 1.73 per 10 ml/min per 1.73 m(2) increase). During the median follow-up of 6.3 years, 1317 patients experienced a cardiovascular event, including 711 myocardial infarctions, 369 strokes, and 735 vascular cause deaths. A total of 1462 patients died of any cause and 52 patients developed ESRD. Irrespective of eGFR, patients in the third tertile of kidney length (11.7-16.1 cm) were at higher risk of cardiovascular mortality (hazard ratio, 1.33; 95% CI, 1.05 to 1.67) and cardiovascular events (hazard ratio, 1.28; 95% CI, 1.09 to 1.50). Patients in the first tertile of kidney length (7.8-10.8 cm) were not at higher risk of cardiovascular adverse events. CONCLUSIONS: Large kidney length is related to higher risk of cardiovascular events and mortality in high-risk patients, irrespective of eGFR. Kidney length may serve as a clinical marker to further identify patients at high cardiovascular risk.

Patients with end-stage renal disease (ESRD) have an increased risk of cardiovascular morbidity and mortality. Cardiac risk assessment, though challenging, is critical in these high-risk patients, particularly in the pre-transplant population. In this review, we discuss the burden of coronary artery disease in the ESRD population and review the literature on the diagnostic and prognostic performance, clinical value, and future directions of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in ESRD patients. Stress myocardial perfusion imaging provides incremental prognostic value to clinical data. The American Heart Association/American College of Cardiology Foundation consensus statement on the cardiac assessment of kidney transplant candidates provides some guidance on the selection of asymptomatic patients for further non-invasive risk stratification. Additionally, the novel selective A2A receptor-agonist vasodilator stress agent, regadenoson, is safe and effective in ESRD and has recently been approved by the Food and Drug Administration for use in this population. Ancillary stress MPI findings, namely heart rate response to vasodilator stress, can provide incremental risk stratification. While myocardial perfusion imaging is widely used as a risk assessment tool, its utilization and clinical implications in the ESRD population are controversial. Though stress SPECT-MPI has imperfect diagnostic accuracy in this specific patient population, it is still a valuable non-invasive modality in cardiovascular risk assessment.