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Chronic kidney disease affects an estimated 37 million people in the United States; of these,>800,000 have end-stage renal disease requiring chronic dialysis or a kidney transplant to survive. Despite efforts to increase the donor kidney supply, approximately 100,000 people are registered on the kidney transplant wait-list with no measurable decrease over the past 2 decades. The outcomes of kidney transplantation are significantly better than for chronic dialysis: kidney transplant recipients have lower rates of mortality and cardiovascular events and better quality of life, but wait-list time matters. Time on dialysis waiting for a deceased-donor kidney is a strong independent risk factor for outcomes after a kidney transplant. Deceased-donor recipients with wait-list times on dialysis of<6 months have graft survival rates equivalent to living-donor recipients with waitlist times on dialysis of>2 years. In 2021,>12,000 people had been on the kidney transplant waitlist for ≥5 years. As the gap between the demand for and availability of donor kidneys for allotransplantation continues to widen, alternative strategies are needed to provide a stable, sufficient, and timely supply. A strategy that is gaining momentum toward clinical application is pig-to-human kidney xenotransplantation. This report summarizes the proceedings of a meeting convened on April 11-12, 2022, by the National Kidney Foundation to review and assess the state of pig-to-human kidney xenotransplantation as a potential cure for end-stage renal disease., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Delayed graft function (DGF) is a common complication after kidney transplant. Despite extensive literature on the topic, the extant definition of DGF has not been conducive to advancing the scientific understanding of the influences and mechanisms contributing to its onset, duration, resolution, or long-term prognostic implications. In 2022, the National Kidney Foundation sponsored a multidisciplinary scientific workshop to comprehensively review the current state of knowledge about the diagnosis, therapy, and management of DGF and conducted a survey of relevant stakeholders on topics of clinical and regulatory interest. In this Special Report, we propose and defend a novel taxonomy for the clinical and research definitions of DGF, address key regulatory and clinical practice issues surrounding DGF, review the current state of therapies to reduce and/or attenuate DGF, offer considerations for clinical practice related to the outpatient management of DGF, and outline a prospective research and policy agenda., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Rationale & Objectives: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD., Study Design: Prospective cohort study., Setting & Participants: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419)., Predictors: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function)., Outcomes: Markers of inflammation (interleukin 1β [IL-1β], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin)., Analytical Approach: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates., Results: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2±14.6 (SD) mL/min/1.73m 2 . More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors., Limitations: Lack of longitudinal data and dietary details., Conclusions: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Quality metrics have a long history in the field of kidney transplantation. These metrics are highly visible, with significant ramifications to transplantation centers based on their use in regulatory review and other stakeholders. In this perspective, we review the history of quality metrics in this field, discuss the perceptions and empirical evidence evaluating the impact of metrics on care delivery, and summarize the current landscape of quality oversight. Based on the research findings and opinions of the transplantation community, we suggest that significant reforms are needed for the evaluation of quality in the field based on more appropriately aligning metrics with optimizing patient outcomes. Moreover, there are vast potential uses of the current data that should be emphasized in a learning environment rather than a highly punitive system. In our view, these reforms would enhance care delivery, improve patient care, and better align incentives for providers of care that treat transplantation patients., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: The effects of underlying noncodified risks are unclear on the prognosis of patients with end-stage renal disease (ESRD). We aimed to evaluate the association of residential area life expectancy with outcomes and processes of care for patients with ESRD in the United States., Study Design: Retrospective cohort study., Setting & Participants: Adult patients with incident ESRD between 2006 and 2013 recorded in the US Renal Data System (n=606,046)., Predictor: The primary exposure was life expectancy in the patient's residential county estimated by the Institute for Health Metrics and Evaluation., Outcomes: Death, placement on the kidney transplant wait list, living and deceased donor kidney transplantation, and posttransplantation graft loss., Results: Median life expectancies of patients' residences were 75.6 (males) and 80.4 years (females). Compared to the highest life expectancy quintile and adjusted for demographic factors, disease cause, and multiple comorbid conditions, the lowest quintile had adjusted HRs for mortality of 1.20 (95% CI, 1.18-1.22); placement onto the waiting list, 0.68 (95% CI, 0.67-0.70); living donor transplantation, 0.53 (95% CI, 0.51-0.56); posttransplantation graft loss, 1.35 (95% CI, 1.27-1.43); and posttransplantation mortality, 1.29 (95% CI, 1.19-1.39). Patients living in areas with lower life expectancy were less likely to be informed about transplantation, be under the care of a nephrologist, or receive an arteriovenous fistula as the initial dialysis access. Results remained consistent with additional adjustment for zip code-level median income, population size, and urban-rural locality., Limitations: Potential residual confounding and attribution of effects to individuals based on residential area-level data., Conclusions: Residential area life expectancy, a proxy for socioeconomic, environmental, genetic, and behavioral factors, was independently associated with mortality and process-of-care measures for patients with ESRD. These results emphasize the underlying effect on health outcomes of the environment in which patients live, independent of patient-level factors. These findings may have implications for provider assessments., (Copyright © 2018 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Diabetes is the leading cause of end-stage renal disease (ESRD) and a significant contributor to mortality in the general population. We examined the associations of hemoglobin A 1c (HbA 1c ) levels with ESRD and death in a population with diabetes and chronic kidney disease (CKD)., Study Design: Cohort study., Setting & Participants: 6,165 patients with diabetes (treated with oral hypoglycemic agents and/or insulin) and CKD stages 1 to 5 at a large health care system., Predictor: HbA 1c level (examined as a categorical and continuous measure)., Outcomes: All-cause and cause-specific mortality ascertained from the Ohio Department of Health mortality files and ESRD ascertained from the US Renal Data System., Results: During a median 2.3 years of follow-up, 957 patients died (887 pre-ESRD deaths) and 205 patients reached ESRD. In a Cox proportional hazards model, after multivariable adjustment including for kidney function, HbA 1c level < 6% was associated with higher risk for death when compared with HbA 1c levels of 6% to 6.9% (HR, 1.23; 95% CI, 1.01-1.50). Similarly, HbA 1c level ≥ 9% was associated with higher risk for all-cause death (HR, 1.34; 95% CI, 1.06-1.69). In competing-risk models, baseline HbA 1c level was not associated with ESRD. For cause-specific mortality, diabetes accounted for >12% of deaths overall and >19% of deaths among those with HbA 1c levels > 9%., Limitations: Small proportion of participants with advanced kidney disease; single-center population., Conclusions: In this cohort of patients with CKD with diabetes, HbA 1c levels < 6% and ≥9% were associated with higher risk for death. HbA 1c levels were not associated with ESRD in this specific CKD population. Diabetes-related deaths increased with higher HbA 1c levels., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Prevalence and factors associated with obstructive and restrictive lung function in people with chronic kidney disease (CKD) are unknown., Study Design: Cross-sectional and longitudinal analyses., Setting & Participants: Participants aged 40 to 79 years from NHANES (National Health and Nutrition Examination Survey) 2007 to 2012 who underwent spirometry testing., Predictor: CKD (estimated glomerular filtration rate [eGFR] >15-<60mL/min/1.73m(2) or urinary albumin-creatinine ratio ≥ 30mg/g)., Outcomes: Restrictive lung function (defined as FEV1/FVC≥0.70 and baseline FVC<80% predicted), obstructive lung function (defined as FEV1/FVC<0.70 based on postbronchodilator spirometric results), and mortality data (available for 2007-2008 and 2009-2010 survey periods)., Results: 7,610 participants (CKD=1,338; non-CKD=6,272) were included. Prevalences of obstructive lung function adjusted to the mean age of 55 years and 50% men in the CKD and non-CKD groups were 15.6% and 13.3%, respectively (P=0.2). Similarly, adjusted prevalences of restrictive lung function in the CKD and non-CKD groups were 9.8% and 6.7%, respectively (P=0.01). Presence of albumin-creatinine ratio ≥ 30mg/g was associated with obstructive (OR, 1.42; 95% CI, 1.07-1.88) and restrictive lung function (OR, 1.43; 95% CI, 1.01-2.03) in the entire study cohort. eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. In a multivariable Cox model, age (HR, 1.07; 95% CI, 1.04-1.11) and presence of obstructive lung function (HR, 2.68; 95% CI, 1.80-3.97), but not CKD measures, were associated with death., Limitations: Small proportion of participants with advanced kidney disease., Conclusions: In a representative sample of US adults, impaired lung function is common in those with and without CKD. Albuminuria was independently associated with both obstructive and restrictive lung function, and eGFR<60mL/min/1.73m(2) was associated with higher odds of obstructive lung function. Older age and obstructive lung function were associated with higher likelihood of death. Further studies examining the burden of lung disease in advanced CKD are needed., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hypogonadism in men (total testosterone <350 ng/dL) is associated with higher risk of cardiovascular disease and mortality in men on dialysis therapy. We evaluated the association of hypogonadism with all-cause mortality in men with non-dialysis-dependent chronic kidney disease (CKD)., Study Design: Retrospective, cohort study., Setting & Participants: 2,419 men with CKD stages 3-4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m2) who had total testosterone measured for cause between January 1, 2005, and October 31, 2011, at a tertiary-care center in Cleveland, OH., Predictors: Total testosterone measured using an immunoassay measurement in 3 forms: (1) categorized as low or testosterone replacement therapy versus normal, (2) continuous log testosterone, and (3) quintiles (100-226, 227-305, 306-392, 393-511, and 512-3,153 ng/dL)., Outcomes: Factors associated with low total testosterone level and the association between low total testosterone level and all-cause mortality were evaluated using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves., Results: Hypogonadism was found in 1,288 of 2,419 (53%) men. In a multivariable logistic regression analysis, African American ethnicity and higher estimated glomerular filtration rate were associated with lower odds of having hypogonadism. Diabetes and higher body mass index were associated with higher odds of having hypogonadism. 357 of 2,419 (15%) patients died during a median follow-up of 2.3 years. In the multivariate Cox model, testosterone level <350 ng/dL or testosterone replacement therapy was not associated with mortality. In a multivariable model also adjusted for testosterone supplementation, higher log testosterone was associated with significantly lower mortality (HR per 1 log unit, 0.70; 95% CI, 0.55-0.89). When compared to the highest quintile, the second lowest quintile of testosterone was associated with higher mortality (HR, 1.53; 95% CI, 1.09-2.16)., Limitations: Single-center study, timing of testosterone testing, lack of adjustment for proteinuria, and sampling bias., Conclusions: Low total testosterone level may be associated with higher mortality in men with CKD stages 3-4, but more studies are needed., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias., Study Design: Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2))., Setting & Participants: Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart., Predictors: Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation≥10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying., Outcomes: Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009., Results: The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11)., Limitations: Interpolated eGFR, moderate sample size, and likely unmeasured confounders., Conclusions: In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients., Study Design: Retrospective cohort study., Setting & Participants: 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation., Predictor: ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure., Outcomes & Measurements: All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System., Results: After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively., Limitations: Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias., Conclusions: Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hospital admissions over weekends have been associated with worse outcomes in different patient populations. The cause of this difference in outcomes remains unclear; however, different staffing patterns over weekends have been speculated to contribute. We evaluated outcomes in patients on maintenance dialysis therapy admitted over weekends using a national database., Study Design: Retrospective cohort study., Setting & Participants: We included nonelective admissions of adult patients (≥18 years) on maintenance dialysis therapy (n = 3,278,572) identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for 2005-2009 using the Nationwide Inpatient Sample database., Predictor: Weekend versus weekday admission., Outcomes: The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included mortality by day 3 of admission, length of hospital stay, time to death, and discharge disposition., Measurements: We adjusted for patient and hospital characteristics, payer, year, comorbid conditions, and primary discharge diagnosis common to maintenance dialysis patients., Results: There were an estimated 704,491 admissions over weekends versus 2,574,081 over weekdays. Unadjusted all-cause in-hospital mortality was 40,666 (5.8%) for weekend admissions in comparison to 138,517 (5.4%) for weekday admissions (P < 0.001). In a multivariable model, patients admitted over weekends had higher all-cause in-hospital mortality (OR, 1.06; 95% CI, 1.01-1.10) in comparison to those admitted over weekdays and higher mortality during the first 3 days of admission (OR, 1.18; 95% CI, 1.10-1.26). Patients admitted over weekends were less likely to be discharged to home, had longer hospital stays, and had shorter times to death compared with those admitted over weekdays on adjusted analysis., Limitations: Use of ICD-9-CM codes to identify patients, defining weekend as midnight Friday to midnight Sunday., Conclusions: Maintenance dialysis patients admitted over weekends have increased mortality rates and longer lengths of stay compared with those admitted over weekdays. Further studies are needed to identify the reasons for worse outcomes for weekend admissions in this patient population., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Accurate prediction of cardiac surgery-associated acute kidney injury (AKI) would improve clinical decision making and facilitate timely diagnosis and treatment. The aim of the study was to develop predictive models for cardiac surgery-associated AKI using presurgical and combined pre- and intrasurgical variables., Study Design: Prospective observational cohort., Settings & Participants: 25,898 patients who underwent cardiac surgery at Cleveland Clinic in 2000-2008., Predictor: Presurgical and combined pre- and intrasurgical variables were used to develop predictive models., Outcomes: Dialysis therapy and a composite of doubling of serum creatinine level or dialysis therapy within 2 weeks (or discharge if sooner) after cardiac surgery., Results: Incidences of dialysis therapy and the composite of doubling of serum creatinine level or dialysis therapy were 1.7% and 4.3%, respectively. Kidney function parameters were strong independent predictors in all 4 models. Surgical complexity reflected by type and history of previous cardiac surgery were robust predictors in models based on presurgical variables. However, the inclusion of intrasurgical variables accounted for all explained variance by procedure-related information. Models predictive of dialysis therapy showed good calibration and superb discrimination; a combined (pre- and intrasurgical) model performed better than the presurgical model alone (C statistics, 0.910 and 0.875, respectively). Models predictive of the composite end point also had excellent discrimination with both presurgical and combined (pre- and intrasurgical) variables (C statistics, 0.797 and 0.825, respectively). However, the presurgical model predictive of the composite end point showed suboptimal calibration (P < 0.001)., Limitations: External validation of these predictive models in other cohorts is required before wide-scale application., Conclusions: We developed and internally validated 4 new models that accurately predict cardiac surgery-associated AKI. These models are based on readily available clinical information and can be used for patient counseling, clinical management, risk adjustment, and enrichment of clinical trials with high-risk participants., (Copyright © 2012 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Low 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear., Study Design: Retrospective cohort study., Setting & Participants: Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System., Predictor: 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL., Outcomes: We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves., Measurements: 25(OH)D was measured using chemiluminescence immunoassay., Results: Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL., Limitations: Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias., Conclusions: 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD., (Copyright © 2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)