American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis, which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

Kidney and cardiovascular-protective benefits of combination drug therapies in chronic kidney disease associated with type 2 diabetes.

Given the substantial burden of chronic kidney disease associated with type 2 diabetes, an aggressive approach to treatment is required. Despite the benefits of guideline-directed therapy, there remains a high residual risk of continuing progression of chronic kidney disease and of cardiovascular events. Historically, a linear approach to pharmacologic management of chronic kidney disease has been used, in which drugs are added, then adjusted, optimized, or stopped in a stepwise manner based on their efficacy, toxicity, effects on a patient's quality of life, and cost. However, there are disadvantages to this approach, which may result in missing a window of opportunity to slow chronic kidney disease progression. Instead, a pillar approach has been proposed to enable earlier treatment that simultaneously targets multiple pathways involved in disease progression. Combination therapy in patients with chronic kidney disease associated with type 2 diabetes is being investigated in several clinical trials. In this article, we discuss current treatment options for patients with chronic kidney disease associated with type 2 diabetes and provide a rationale for tailored combinations of therapies with complementary mechanisms of action to optimize therapy using a pillar-based treatment strategy. [This article includes a plain language summary as an additional file].

Racial and Ethnic Disparities in Kidney Replacement Therapies Among Adults With Kidney Failure: An Observational Study of Variation by Patient Age.

RATIONALE & OBJECTIVE: Non-Hispanic Black and Hispanic patients present with kidney failure at younger ages than White patients. Younger patients are also more likely to receive transplants and home dialysis than in-center hemodialysis (ICHD), but it is unknown whether racial and ethnic disparities in treatment differ by age. We compared use of kidney replacement therapies between racial and ethnic groups among patients with incident kidney failure overall and by age. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 830,402 US adult (age >21 years) patients initiating kidney failure treatment during the period of 2011-2018. EXPOSURES: Patient race and ethnicity (non-Hispanic Black, non-Hispanic White, Hispanic, or other) and age group (22-44, 45-64, 65-74, or 75-99 years). OUTCOME: Treatment modality (transplant, peritoneal dialysis [PD], home hemodialysis [HHD], or ICHD) as of day 90 of treatment. ANALYTICAL APPROACH: Differences in treatment modalities were quantified for patient subgroups defined by race and ethnicity and by age. Log-binomial regression models were fit to estimate adjusted risk ratios. RESULTS: 81% of patients were treated with ICHD, 3.0% underwent transplants (85% preemptive, 57% living-donor), 10.5% were treated with PD, and 0.7% were treated with HHD. Absolute disparities in treatment were most pronounced among patients aged 22-44 years. Compared with non-Hispanic White patients, whose percentages of treatment with transplant, PD, and HHD were 10.9%, 19.0%, and 1.2%, respectively, non-Hispanic Black patients were less commonly treated with each modality (unadjusted percentages, 1.8%, 13.8%, and 0.6%, respectively), as were Hispanic patients (4.4%, 16.9%, and 0.5%, respectively; all differences P < 0.001). After adjustment, the largest relative disparities were observed for transplant among the 22-44-year age group; compared with non-Hispanic White patients, the adjusted risk ratios for non-Hispanic Black and Hispanic patients were 0.21 (95% CI, 0.19-0.23) and 0.47 (95% CI, 0.43, 0.51), respectively. LIMITATIONS: Race and ethnicity data not self-reported. CONCLUSIONS: Among adults with incident kidney failure, racial and ethnic disparities in transplant and home dialysis use are most pronounced among the youngest adult patient age group.

Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial.

BACKGROUND: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications. METHODS: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the UK, and the USA, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline-adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749. FINDINGS: From June 25, 2015, to Oct 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months. INTERPRETATION: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications. FUNDING: Medtronic.

Epidemiology of COVID-19 Infection in Hospitalized End-Stage Kidney Disease Patients in a Predominantly African-American Population.

BACKGROUND: End-stage kidney disease patients on dialysis are particularly susceptible to COVID-19 infection due to comorbidities, age, and logistic constraints of dialysis making social distancing difficult. We describe our experience with hospitalized dialysis patients with COVID-19 and factors associated with mortality. METHODS: From March 1, 2020, to May 31, 2020, all dialysis patients admitted to 4 Emory Hospitals and tested for COVID-19 were identified. Sociodemographic information and clinical and laboratory data were obtained from the medical record. Death was defined as an in-hospital death or transfer to hospice for end-of-life care. Patients were followed until discharge or death. RESULTS: Sixty-four dialysis patients with COVID-19 were identified. Eighty-four percent were African-American. The median age was 64 years, and 59% were males. Four patients were on peritoneal dialysis, and 60 were on hemodialysis for a median time of 3.8 years, while 31% were obese. Fever (72%), cough (61%), and diarrhea (22%) were the most common symptoms at presentation. Thirty-three percent required admission to intensive care unit, and 23% required mechanical ventilation. The median length of stay was 10 days, while 11 patients (17%) died during hospitalization and 17% were discharged to a temporary rehabilitation facility. Age >65 years (RR 13.7, CI: 1.9-100.7), C-reactive protein >100 mg/dL (RR 8.3, CI: 1.1-60.4), peak D-dimer >3,000 ng/mL (RR 4.3, CI: 1.03-18.2), bilirubin >1 mg/dL (RR 3.9, CI: 1.5-10.4), and history of peripheral vascular disease (RR 3.2, CI: 1.2-9.1) were associated with mortality. Dialysis COVID-19-infected patients were more likely to develop thromboembolic complications than those without COVID-19 (RR 3.7, CI: 1.3-10.1). CONCLUSION: In a predominantly African-American population, the mortality of end-stage kidney disease patients admitted with COVID-19 infection was 17%. Age, C-reactive protein, D-dimer, bilirubin, and history of peripheral vascular disease were associated with worse survival.

COVID-19 infection control measures and outcomes in urban dialysis centers in predominantly African American communities.

BACKGROUND: Emory Dialysis serves an urban and predominantly African American population at its four outpatient dialysis facilities. We describe COVID-19 infection control measures implemented and clinical characteristics of patients with COVID-19 in the Emory Dialysis facilities. METHODS: Implementation of COVID-19 infection procedures commenced in February 2020. Subsequently, COVID-19 preparedness assessments were conducted at each facility. Patients with COVID-19 from March 1-May 31, 2020 were included; with a follow-up period spanning March-June 30, 2020. Percentages of patients diagnosed with COVID-19 were calculated, and characteristics of COVID-19 patients were summarized as medians or percentage. Baseline characteristics of all patients receiving care at Emory Dialysis (i.e. Emory general dialysis population) were presented as medians and percentages. RESULTS: Of 751 dialysis patients, 23 (3.1%) were diagnosed with COVID-19. The median age was 67.0 years and 13 patients (56.6%) were female. Eleven patients (47.8%) were residents of nursing homes. Nineteen patients (82.6%) required hospitalization and 6 patients (26.1%) died; the average number of days from a positive SARS-CoV-2 (COVID) test to death was 16.8 days (range 1-34). Two patients dialyzing at adjacent dialysis stations and a dialysis staff who cared for them, were diagnosed with COVID-19 in a time frame that may suggest transmission in the dialysis facility. In response, universal masking in the facility was implemented (prior to national guidelines recommending universal masking), infection control audits and re-trainings of PPE were also done to bolster infection control practices. CONCLUSION: We successfully implemented recommended COVID-19 infection control measures aimed at mitigating the spread of SARS-CoV-2. Most of the patients with COVID-19 required hospitalizations. Dialysis facilities should remain vigilant and monitor for possible transmission of COVID-19 in the facility.

Making sense of DialysisConnect: a qualitative analysis of stakeholder viewpoints on a web-based information exchange platform to improve care transitions between dialysis clinics and hospitals.

BACKGROUND: U.S. hospitals and dialysis centers are penalized for 30-day hospital readmissions of dialysis patients, despite little infrastructure to facilitate care transitions between these settings. We are developing a third-party web-based information exchange platform, DialysisConnect, to enable clinicians to view and exchange information about dialysis patients during admission, hospitalization, and discharge. This health information technology solution could serve as a flexible and relatively affordable solution for dialysis facilities and hospitals across the nation who are seeking to serve as true partners in the improved care of dialysis patients. The purpose of this study was to evaluate the perceived coherence of DialysisConnect to key clinical stakeholders, to prepare messaging for implementation. METHODS: As part of a hybrid effectiveness-implementation study guided by Normalization Process Theory, we collected data on stakeholder perceptions of continuity of care for patients receiving maintenance dialysis and a DialysisConnect prototype before completing development and piloting the system. We conducted four focus groups with stakeholders from one academic hospital and associated dialysis centers [hospitalists (n = 5), hospital staff (social workers, nurses, pharmacists; n = 9), nephrologists (n = 7), and dialysis clinic staff (social workers, nurses; n = 10)]. Transcriptions were analyzed thematically within each component of the construct of coherence (differentiation, communal specification, individual specification, and internalization). RESULTS: Participants differentiated DialysisConnect from usual care variously as an information dashboard, a quick-exchange communication channel, and improved discharge information delivery; some could not differentiate it in terms of workflow. The purpose of DialysisConnect (communal specification) was viewed as fully coherent only for communicating outside of the same healthcare system. Current system workarounds were acknowledged as deterrents for practice change. All groups delegated DialysisConnect tasks (individual specification) to personnel besides themselves. Partial internalization of DialysisConnect was achieved only by dialysis clinic staff, based on experience with similar technology. CONCLUSIONS: Implementing DialysisConnect for clinical users in both settings will require presenting a composite picture of current communication processes from all stakeholder groups to correct single-group misunderstandings, as well as providing data about care transitions communication beyond the local context to ease resistance to practice change.

Long-term outcomes among Medicare patients readmitted in the first year of hemodialysis: a retrospective cohort study.

BACKGROUND: Readmission within 30 days of hospital discharge is common and costly among end-stage renal disease (ESRD) patients. Little is known about long-term outcomes after readmission. We estimated the association between hospital admissions and readmissions in the first year of dialysis and outcomes in the second year. METHODS: Data on incident dialysis patients with Medicare coverage were obtained from the United States Renal Data System (USRDS). Readmission patterns were summarized as no admissions in the first year of dialysis (Admit-), at least one admission but no readmissions within 30 days (Admit+/Readmit-), and admissions with at least one readmission within 30 days (Admit+/Readmit+).We used Cox proportional hazards models to estimate the association between readmission pattern and mortality, hospitalization, and kidney transplantation, accounting for demographic and clinical covariates. RESULTS: Among the 128,593 Medicare ESRD patients included in the study, 18.5% were Admit+/Readmit+, 30.5% were Admit+/Readmit-, and 51.0% were Admit-. Readmit+/Admit+ patients had substantially higher long-term risk of mortality (HR = 3.32 (95% CI, 3.21-3.44)), hospitalization (HR = 4.46 (95% CI, 4.36-4.56)), and lower likelihood of kidney transplantation (HR = 0.52 (95% CI, 0.44-0.62)) compared to Admit- patients; these associations were stronger than those among Admit+/Readmit- patients. CONCLUSIONS: Patients with readmissions in the first year of dialysis were at substantially higher risk of poor outcomes than either patients who had no admissions or patients who had hospital admissions but no readmissions. Identifying strategies to both prevent readmission and mitigate risk among patients who had a readmission may improve outcomes among this substantial, high-risk group of ESRD patients.

Delivery of a patient-friendly functioning report to improve patient-centeredness of dialysis care: a pilot study.

BACKGROUND: Provider recognition of level of functioning may be suboptimal in the dialysis setting, and this lack of recognition may lead to less patient-centered care. We aimed to assess whether delivery of an app-based, individualized functioning report would improve patients' perceptions of patient-centeredness of care. METHODS: In this pre-post pilot study at three outpatient dialysis facilities in metropolitan Atlanta, an individualized functioning report-including information on physical performance, perceived physical functioning, and community mobility-was delivered to patients receiving hemodialysis (n = 43) and their providers. Qualitative and quantitative approaches were used to gather patient and provider feedback to develop and assess the report and app. Paired t test was used to test for differences in patient perception of patient-centeredness of care (PPPC) scores (range, 1 = most patient-centered to 4 = least patient-centered) 1 month after report delivery. RESULTS: Delivery of the reports to both patients and providers was not associated with a subsequent change in patients' perceptions of patient-centeredness of their care (follow-up vs. baseline PPPC scores of 2.35 vs. 2.36; P > 0.9). However, patients and providers generally saw the potential of the report to improve the patient-centeredness of care and reacted positively to the individualized reports delivered in the pilot. Patients also reported willingness to undergo future assessments. However, while two-thirds of surveyed providers reported always or sometimes discussing the reports they received, most (98%) participating patients reported that no one on the dialysis care team had discussed the report with them within 1 month. CONCLUSIONS: Potential lack of fidelity to the intervention precludes definitive conclusions about effects of the report on patient-centeredness of care. The disconnect between patients' and providers' perceptions of discussions of the report warrants future study. However, this study introduces a novel, individualized, multi-domain functional report that is easily implemented in the setting of hemodialysis. Our pilot study provides guidance for improving its use both clinically and in future pragmatic research studies, both within and beyond the dialysis population.

Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial.

BACKGROUND: Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. METHODS: SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. FINDINGS: Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP -5·5 mm Hg (95% CI -9·1 to -2·0; p=0·0031), 24-h DBP -4·8 mm Hg (-7·0 to -2·6; p<0·0001), office SBP -10·0 mm Hg (-15·1 to -4·9; p=0·0004), and office DBP -5·3 mm Hg (-7·8 to -2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP -0·5 mm Hg (95% CI -3·9 to 2·9; p=0·7644), 24-h DBP -0·4 mm Hg (-2·2 to 1·4; p=0·6448), office SBP -2·3 mm Hg (-6·1 to 1·6; p=0·2381), and office DBP -0·3 mm Hg (-2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP -5·0 mm Hg (95% CI -9·9 to -0·2; p=0·0414), 24-h DBP -4·4 mm Hg (-7·2 to -1·6; p=0·0024), office SBP -7·7 mm Hg (-14·0 to -1·5; p=0·0155), and office DBP -4·9 mm Hg (-8·5 to -1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. INTERPRETATION: Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. FUNDING: Medtronic.

Burden and correlates of readmissions related to pulmonary edema in US hemodialysis patients: a cohort study.

Background: Pulmonary edema is prevalent and may be a common cause of hospital readmissions in hemodialysis patients. We aimed to estimate the national burden of, and identify correlates of, readmissions related to pulmonary edema among hemodialysis patients. Methods: In this retrospective cohort study using national registry data, we identified prevalent US hemodialysis patients (n = 215 251) with index admissions while under Medicare primary coverage in 2011-13. We defined readmissions as admissions occurring within 30 days of the index discharge and pulmonary edema-related readmissions as readmissions with discharge diagnoses of fluid overload, heart failure or pulmonary edema. Multivariable logistic regression models were used to determine odds ratios (ORs) for pulmonary edema-related readmissions by patient and index admission characteristics. Results: About one-quarter (23%) of index hospital admissions were followed by a readmission, with nearly half (44%) of the readmissions being associated with pulmonary edema. The strongest independent correlate of pulmonary edema-related readmission was a pulmonary edema-related index admission [OR = 2.32; 95% confidence interval (CI) 2.22-2.41]. With the exception of dialysis vintage <1 year (OR = 1.18; 95% CI 1.14-1.22), chronic obstructive pulmonary disease (OR = 1.34; 95% CI 1.29-1.38), dialysis non-compliance (OR = 1.53; 95% CI 1.41-1.64) and congestive heart failure (OR = 1.85; 95% CI 1.77-1.93), patient characteristics were not generally associated with higher risk of pulmonary edema-related readmission. Conclusions: Readmissions related to pulmonary edema are common in hemodialysis patients. Interventions aimed at preventing such readmissions could have a substantial impact on readmissions overall, particularly targeted at incident hemodialysis patients with a prior history of heart failure and patients initially admitted for pulmonary edema.

Post-hospitalization dialysis facility processes of care and hospital readmissions among hemodialysis patients: a retrospective cohort study.

BACKGROUND: Both dialysis facilities and hospitals are accountable for 30-day hospital readmissions among U.S. hemodialysis patients. We examined the association of post-hospitalization processes of care at hemodialysis facilities with pulmonary edema-related and other readmissions. METHODS: In a retrospective cohort comprised of electronic medical record (EMR) data linked with national registry data, we identified unique patient index admissions (n = 1056; 2/1/10-7/31/15) that were followed by ≥3 in-center hemodialysis sessions within 10 days, among patients treated at 19 Southeastern dialysis facilities. Indicators of processes of care were defined as present vs. absent in the dialysis facility EMR. Readmissions were defined as admissions within 30 days of the index discharge; pulmonary edema-related vs. other readmissions defined by discharge codes for pulmonary edema, fluid overload, and/or congestive heart failure. Multinomial logistic regression to estimate odds ratios (ORs) for pulmonary edema-related and other vs. no readmissions. RESULTS: Overall, 17.7% of patients were readmitted, and 8.0% had pulmonary edema-related readmissions (44.9% of all readmissions). Documentation of the index admission (OR = 2.03, 95% CI 1.07-3.85), congestive heart failure (OR = 1.87, 95% CI 1.07-3.27), and home medications stopped (OR = 1.81, 95% CI 1.08-3.05) or changed (OR = 1.69, 95% CI 1.06-2.70) in the EMR post-hospitalization were all associated with higher risk of pulmonary edema-related vs. no readmission; lower post-dialysis weight (by ≥0.5 kg) after vs. before hospitalization was associated with 40% lower risk (OR = 0.60, 95% CI 0.37-0.96). CONCLUSIONS: Our results suggest that some interventions performed at the dialysis facility in the post-hospitalization period may be associated with reduced readmission risk, while others may provide a potential existing means of identifying patients at higher risk for readmissions, to whom such interventions could be efficiently targeted.

Association of social worker-assessed psychosocial factors with 30-day hospital readmissions among hemodialysis patients.

BACKGROUND: Evidence regarding the effect of psychosocial factors on hospital readmission in the setting of hemodialysis is limited. We examined whether social worker-assessed factors were associated with 30-day readmission among prevalent hemodialysis patients. METHODS: Data on 14 factors were extracted from the first available psychosocial assessment performed by social workers at three metropolitan Atlanta dialysis centers. Index admissions (first admission preceded by ≥30 days without a previous hospital discharge) were identified in the period 2/1/10-12/31/14, using linked national administrative hospitalization data. Readmission was defined as any admission within 30 days after index discharge. Associations of each of the psychosocial factors with readmission were assessed using multivariable logistic regression with adjustment for patient and index admission characteristics. RESULTS: Among 719 patients with index admissions, 22.1% were readmitted within 30 days. No psychosocial factors were statistically significantly associated with readmission risk. However, history of substance abuse vs. none was associated with a 29% higher risk of 30-day readmission [OR: 1.29, 95% CI: 0.75-2.23], whereas depression/anxiety was associated with 20% lower risk [OR: 0.80, 95% CI: 0.47-1.36]. Patients who were never married and those who were divorced, or widowed had 38 and 17% higher risk of 30-day readmission, respectively, than those who were married [OR: 1.38, 95% CI: 0.84-2.72; OR: 1.17, 95% CI: 0.73-1.90]. CONCLUSIONS: Results suggest that psychosocial issues may be associated with risk of 30-day readmission among dialysis patients. Despite the limitations of lack of generalizability and potential misclassification due to patient self-report of psychosocial factors to social workers, further study is warranted to determine whether addressing these factors through targeted interventions could potentially reduce readmissions among hemodialysis patients.

BP Control and Long-Term Risk of ESRD and Mortality.

We recently showed an association between strict BP control and lower mortality risk during two decades of follow-up of prior participants in the Modification of Diet in Renal Disease (MDRD) trial. Here, we determined the risk of ESRD and mortality during extended follow-up of the African American Study of Kidney Disease and Hypertension (AASK) trial. We linked 1067 former AASK participants with CKD previously randomized to strict or usual BP control (mean arterial pressure ≤92 mmHg or 102-107 mmHg, respectively) to the US Renal Data System and Social Security Death Index; 397 patients had ESRD and 475 deaths occurred during a median follow-up of 14.4 years from 1995 to 2012. Compared with the usual BP arm, the strict BP arm had unadjusted and adjusted relative risks of ESRD of 0.92 (95% confidence interval [95% CI], 0.75 to 1.12) and 0.95 (95% CI, 0.78 to 1.16; P=0.64), respectively, and unadjusted and adjusted relative risks of death of 0.92 (95% CI, 0.77 to 1.10) and 0.81 (95% CI, 0.68 to 0.98; P=0.03), respectively. In meta-analyses of individual-level data from the MDRD and the AASK trials, unadjusted relative risk of ESRD was 0.88 (95% CI, 0.78 to 1.00) and unadjusted relative risk of death was 0.87 (95% CI, 0.76 to 0.99) for strict versus usual BP arms. Our findings suggest that, during long-term follow-up, strict BP control does not delay the onset of ESRD but may reduce the relative risk of death in CKD.

Early hospital readmission among hemodialysis patients in the United States is associated with subsequent mortality.

Dialysis providers in the United States may soon be held accountable for their patients' 30-day hospital readmissions. However, few studies have evaluated the timing of readmissions, which determines the window in which dialysis providers could act to prevent readmission. We therefore examined the timing of readmissions of hemodialysis patients in the United States and its association with mortality among 285,795 prevalent adult Medicare-primary hemodialysis patients from a national registry. Patients had at least one hospitalization in 2010-2013 (first index) and survived for 30 days or more. Readmission timing was defined as 0-7, 8-14, or 15-30 days after the index discharge. Multivariable Cox proportional hazards models were used to estimate the association between readmission timing (referent no readmission) and mortality, censored at one year. Overall, 23.1% of patients had readmissions within 30 days of the index discharge, of which over one-third (35.9%) were within the first week. Regardless of timing, patients with readmissions had a higher risk of death within one year, compared to those with no readmissions, with hazard ratios of 2.04 (95% confidence interval 2.00-2.09) for being readmitted within 15-30 days; 1.98 (1.93-2.04) for being readmitted within 8-14 days; and 1.76 (1.71-1.80) for being readmitted within 0-7 days. Thus, opportunities for dialysis providers to intervene and prevent early readmission may be limited. Regardless of the timing, readmission appears independently associated with a substantially increased risk of mortality in this population.

Past Decline Versus Current eGFR and Subsequent Mortality Risk.

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

APOL1 renal-risk genotypes associate with longer hemodialysis survival in prevalent nondiabetic African American patients with end-stage renal disease.

Relative to European Americans, evidence supports that African Americans with end-stage renal disease (ESRD) survive longer on dialysis. Renal-risk variants in the apolipoprotein L1 gene (APOL1), associated with nondiabetic nephropathy and less subclinical atherosclerosis, may contribute to dialysis outcomes. Here, APOL1 renal-risk variants were assessed for association with dialytic survival in 450 diabetic and 275 nondiabetic African American hemodialysis patients from Wake Forest and Emory School of Medicine outpatient facilities. Outcomes were provided by the ESRD Network 6-Southeastern Kidney Council Standardized Information Management System. Dates of death, receipt of a kidney transplant, and loss to follow-up were recorded. Outcomes were censored at the date of transplantation or through 1 July 2015. Multivariable Cox proportional hazards models were computed separately in patients with nondiabetic and diabetic ESRD, adjusting for the covariates age, gender, comorbidities, ancestry, and presence of an arteriovenous fistula or graft at dialysis initiation. In nondiabetic ESRD, patients with 2 (vs. 0/1) APOL1 renal-risk variants had significantly longer dialysis survival (hazard ratio 0.57), a pattern not observed in patients with diabetes-associated ESRD (hazard ratio 1.29). Thus, 2 APOL1 renal-risk variants are associated with longer dialysis survival in African Americans without diabetes, potentially relating to presence of renal-limited disease or less atherosclerosis.

The ras responsive transcription factor RREB1 is a novel candidate gene for type 2 diabetes associated end-stage kidney disease.

Familial clustering and presumed genetic risk for type 2 diabetic (T2D) and non-diabetic end-stage kidney disease (ESKD) appear strong in African Americans. Examination of exome sequencing data in African American T2D-ESKD cases and non-diabetic non-nephropathy controls identified two low-frequency variants in the RREB1 gene, a repressor of the angiotensinogen (AGT) gene previously associated with kidney function, as being associated with T2D-ESKD: rs9379084 (P = 0.00087, OR = 0.26; D1171N) and rs41302867 (P = 0.00078, OR = 0.21; splice site variant). Rs41302867 replicated association in an independent sample of African Americans with T2D-ESKD [rs41302867 P = 0.033 (OR = 0.50)], and a trend towards rs9379084 association was observed (P = 0.070). In European Americans with T2D-ESKD compared with European American population based controls, both RREB1 variants replicated association [rs9379084 P = 1.67 × 10(-4) (OR = 0.54) and rs41302867 P = 0.013 (OR = 0.69)]. Rs9379084 was not associated with non-T2D-ESKD or T2D in African Americans (P = 0.55 and P = 0.37, respectively), but was associated with T2D in European Americans (P = 0.014, OR = 0.65). In African Americans, rs41302867 was associated with non-T2D-ESKD [P = 0.036 (OR = 0.54)] and hypertension attributed ESKD [H-ESKD, P = 0.029 (OR = 0.50)]. A meta-analysis combining African American and European American T2D-ESKD data revealed P = 3.52 × 10(-7) and 3.70 × 10(-5) for rs9379084 and rs41302867 association, respectfully. A locus-wide analysis evaluating putatively functional SNPs revealed several nominal associations with T2D-ESKD, non-T2D-ESKD and T2D in African and European Americans. RREB1 is a large, complex gene which codes a multidomain zinc finger binding protein and transcription factor. We posit that variants in RREB1 modulate seemingly disparate phenotypes (i.e. T2D, T2D-ESKD and non-T2D-ESKD) through altered activity resulting from splice site and missense variants.

Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD.

Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes-associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility.