Acute Kidney Injury in Deceased Organ Donors and Kidney Transplant Outcomes: A National Cohort Study Using a Novel Data Source.

OBJECTIVE: The aim of this study was to determine graft function and survival for kidney transplants from deceased donors with acute kidney injury (AKI) that persists at the time of organ procurement. BACKGROUND: Kidneys from donors with AKI are often discarded and may provide an opportunity to selectively expand the donor pool. METHODS: Using Organ Procurement and Transplantation Network and DonorNet data, we studied adult kidney-only recipients between May 1, 2007 and December 31, 2016. DonorNet was used to characterize longitudinal creatinine trends and urine output. Donor AKI was defined using KDIGO guidelines and terminal creatinine ≥1.5 mg/dL. We compared outcomes between AKI kidneys versus "ideal comparator" kidneys from donors with no or resolved AKI stage 1 plus terminal creatinine <1.5mg/dL. We fit proportional hazards models and hierarchical linear regression models for the primary outcomes of all-cause graft failure (ACGF) and 12-month estimated glomerular filtration rate (eGFR), respectively. RESULTS: We identified 7660 donors with persistent AKI (33.2% with AKI stage 3) from whom ≥1 kidney was transplanted. Observed rates of ACGF within 3 years were similar between recipient groups (15.5% in AKI vs 15.1% ideal comparator allografts, P = 0.2). After risk adjustment, ACGF was slightly higher among recipients of AKI kidneys (adjusted hazard ratio 1.05, 95% confidence interval: 1.01-1.09). The mean 12-month eGFR for AKI kidney recipients was lower, but differences were not clinically important (56.6 vs 57.5 mL/min/1.73m 2 for ideal comparator kidneys; P < 0.001). There were 2888 kidneys discarded from donors with AKI, age ≤65 years, without hypertension or diabetes, and terminal creatinine ≤4 mg/dL. CONCLUSION: Kidney allografts from donors with persistent AKI are often discarded, yet those that were transplanted did not have clinically meaningful differences in graft survival and function.

Mortality and Hepatic Decompensation in Patients With Cirrhosis and Atrial Fibrillation Treated With Anticoagulation.

BACKGROUND AND AIMS: Outcomes with anticoagulation (AC) are understudied in advanced liver disease. We investigated effects of AC with warfarin and direct oral anticoagulants (DOACs) on all-cause mortality and hepatic decompensation as well as ischemic stroke, major adverse cardiovascular events, splanchnic vein thrombosis, and bleeding in a cohort with cirrhosis and atrial fibrillation (AF). APPROACH AND RESULTS: This was a retrospective, longitudinal study using national data of U.S. veterans with cirrhosis at 128 medical centers, including patients with cirrhosis with incident AF, from January 1, 2012 to December 31, 2017 followed through December 31, 2018. To assess the effects of AC on outcomes, we applied propensity score (PS) matching and marginal structural models (MSMs) to account for confounding by indication and time-dependent confounding. The final cohort included 2,694 veterans with cirrhosis with AF (n = 1,694 and n = 704 in the warfarin and DOAC cohorts after PS matching, respectively) with a median of 4.6 years of follow-up. All-cause mortality was lower with warfarin versus no AC (PS matched: hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.55-0.76; MSM models: HR, 0.54; 95% CI, 0.40-0.73) and DOACs versus no AC (PS matched: HR, 0.68; 95% CI, 0.50-0.93; MSM models: HR, 0.50; 95% CI, 0.31-0.81). In MSM models, warfarin (HR, 0.29; 95% CI, 0.09-0.90) and DOACs (HR, 0.23; 95% CI, 0.07-0.79) were associated with reduced ischemic stroke. In secondary analyses, bleeding was lower with DOACs compared to warfarin (HR, 0.49; 95% CI, 0.26-0.94). CONCLUSIONS: Warfarin and DOACs were associated with reduced all-cause mortality. Warfarin was associated with more bleeding compared to no AC. DOACs had a lower incidence of bleeding compared to warfarin in exploratory analyses. Future studies should prospectively investigate these observed associations.

Association of Kidney Transplant Center Volume With 3-Year Clinical Outcomes.

RATIONALE & OBJECTIVE: A robust relationship between procedure volume and clinical outcomes has been demonstrated across many surgical fields. This study assessed whether a center volume-outcome relationship exists for contemporary kidney transplantation, specifically for diabetic recipients, older recipients (aged ≥65 years), and recipients of high kidney donor profile index (KDPI ≥ 85) kidneys. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult kidney-only transplant recipients who underwent transplantation between 2009 and 2013 (N = 79,581). EXPOSURES: The primary exposure variable was center volume, categorized into quartiles based on the total kidney transplantation volume. Quartile 1 (Q1) centers performed a mean of fewer than 66 kidney transplantations per year, whereas Q4 centers performed a mean of more than 196 kidney transplantations per year. OUTCOMES: All-cause graft failure and mortality within 3 years of transplantation. ANALYTICAL APPROACH: Multivariable Cox frailty models were used to adjust for donor characteristics, recipient characteristics, and cold ischemia time. RESULTS: Minor differences in rates of 3-year deceased donor all-cause graft failure across quartiles of center volume were observed (14.9% for Q1 vs 16.7% for Q4), including in subgroups (diabetic recipients, 18.4% for Q1 vs 19.7% for Q4; older recipients, 19.4% for Q1 vs 22.5% for Q4; recipients of high KDPI kidneys, 26.5% for Q1 vs 26.5% for Q4). Results were similar for 3-year mortality. After adjustment for donor, recipient, and graft characteristics using Cox regression, center volume was not significantly associated with all-cause graft failure or mortality within 3 years, except that diabetic recipients at Q3 centers had slightly lower mortality (compared with Q1 centers, adjusted HR of 0.85 [95% CI, 0.73-0.99]). LIMITATIONS: Potential unmeasured confounding from patient comorbid conditions and organ selection. CONCLUSIONS: These findings provide little evidence that care in higher volume centers is associated with better adjusted outcomes for kidney transplant recipients, even in populations anticipated to be at increased risk for graft failure or death.

Mortality and Kidney Transplantation Outcomes Among Hepatitis C Virus-Seropositive Maintenance Dialysis Patients: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Hepatitis C virus (HCV) infection is common among maintenance dialysis patients. Few studies have examined both dialysis survival and transplantation outcomes for HCV-seropositive patients because registry data sets lack information for HCV serostatus. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adult long-term dialysis patients treated by a US national dialysis provider between January 1, 2004, and December 31, 2014. EXPOSURE: HCV antibody serostatus obtained as part of clinical data from a national dialysis provider. OUTCOMES: Mortality on dialysis therapy, entry onto the kidney transplant waiting list, kidney transplantation, and estimated survival benefit from kidney transplantation versus remaining on the waitlist. ANALYTICAL APPROACH: After linking clinical data with data from the Organ Procurement and Transplantation Network, Cox and cause-specific hazards regression were implemented to estimate the associations between HCV seropositivity and mortality, as well as entry onto the kidney transplant waitlist. Cox regression was also used to estimate the survival benefit from transplantation versus dialysis among HCV-seropositive individuals. RESULTS: Among 442,171 dialysis patients, 31,624 (7.2%) were HCV seropositive. HCV seropositivity was associated with a small elevation in the rate of death (adjusted HR [aHR], 1.09; 95% CI, 1.07-1.11) and a substantially lower rate of entry onto the kidney transplant waitlist (subdistribution HR [sHR], 0.67; 95% CI, 0.61-0.74). Once wait-listed, the kidney transplantation rate was not different for HCV-seropositive (sHR 1.10; 95% CI, 0.96-1.27) versus HCV-seronegative patients. HCV-seropositive patients lived longer with transplantation (aHR at 3 years, 0.42; 95% CI, 0.27-0.63). Receiving an HCV-seropositive donor kidney provided a survival advantage at the 2-year posttransplantation time point compared to remaining on dialysis therapy waiting for an HCV-negative kidney. LIMITATIONS: No data for HCV viral load or liver biopsy. CONCLUSIONS: HCV-seropositive patients experience reduced access to the kidney transplantation waitlist despite deriving a substantial survival benefit from transplantation. HCV-seropositive patients should consider foregoing HCV treatment while accepting kidneys from HCV-infected donors to facilitate transplantation and prolong survival.

Patient and Kidney Allograft Survival in Recipients With End-Stage Renal Disease From Amyloidosis.

BACKGROUND: Outcomes after kidney transplantation for patients with amyloidosis-associated end-stage renal disease (ESRD) have not been well characterized. METHODS: We performed a retrospective propensity score matched cohort study with Cox proportional hazards modeling using data from the United Network of Organ Sharing including patients transplanted from 1987 to 2015 (N = 310 629). RESULTS: Amyloidosis patients (N = 576) had higher rates of death (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.28-1.95) and graft loss (HR, 1.49; 95% CI, 1.19-1.87) compared with nonamyloidosis patients. The results were similar when the cohort was restricted to patients transplanted on or after 2001 (HR, 1.72; 95% CI, 1.31-2.26 for death; HR, 1.77; 95% CI, 1.35-2.33 for graft loss). However, there was no significant difference in risk of death or graft loss when amyloidosis patients were compared with those with diabetes-associated ESRD (mortality: HR, 0.99; 95% CI, 0.84-1.17; allograft loss: HR, 1.00; 95% CI, 0.84-1.20), or when compared with elderly patients (age, >65 years at the time of transplant) (mortality: HR, 0.99; 95% CI, 0.81-1.21; graft loss: HR, 1.02; 95% CI, 0.82-1.26). CONCLUSIONS: For patients with amyloidosis-associated ESRD deemed suitable for transplantation, patient and graft survivals are diminished compared to kidney transplant recipients overall, but are comparable to other high-risk subgroups.

An Interactive Ambulatory Nephrology Curriculum for Internal Medicine Interns: Design, Implementation, and Participant Feedback.

While diminishing nephrology fellow recruitment is a known issue, more work is needed to evaluate possible interventions to reverse this trend. We designed and implemented a curriculum to increase exposure to ambulatory nephrology among internal medicine interns. The curriculum focused on key aspects of outpatient nephrology practice, including supervised clinic visits, formal themed didactic content, and an online interactive forum with assigned evidence-based readings and small-group responses to relevant cases. We obtained postcourse surveys from all participating interns. Of the 43 interns who took part in the first year of the ambulatory nephrology curriculum, 100% reported a positive didactic experience and 91% reported a positive interactive online experience. 77% reported an improvement in their familiarity with clinical nephrology practice (median 2-point increase in familiarity score on a 7-point scale, P<0.001 by signed rank testing). Qualitative feedback included praise for the high-yield topics covered by the lectures and energizing teachers. In conclusion, we successfully implemented an ambulatory nephrology curriculum using a framework that integrated formal didactics, interactive online learning, and key clinical components of outpatient nephrology care. Future investigation will evaluate whether early implementation of this curriculum is associated with increased pursuit of nephrology as a career.

Belatacept Compared With Tacrolimus for Kidney Transplantation: A Propensity Score Matched Cohort Study.

BACKGROUND: Although tacrolimus is the basis of most maintenance immunosuppression regimens for kidney transplantation, concerns about toxicity have made alternative agents, such as belatacept, attractive to clinicians. However, limited data exist to directly compare outcomes with belatacept-based regimens to tacrolimus. METHODS: We performed a propensity score matched cohort study of adult kidney transplant recipients transplanted between May 1, 2001, and December 31, 2015, using national transplant registry data to compare patient and allograft survival in patients discharged from their index hospitalization on belatacept-based versus tacrolimus-based regimens. RESULTS: In the primary analysis, we found that belatacept was not associated with a statistically significant difference in risk of patient death (hazard ratio, 0.84; 95% confidence interval [CI], 0.61-1.15, P = 0.28) or allograft loss (hazard ratio, 0.83; 95% CI, 0.62-1.11; P = 0.20) despite an increased risk of acute rejection in the first year posttransplant (odds ratio, 3.12; 95% CI, 2.13-4.57; P < 0.001). These findings were confirmed in additional sensitivity analyses that accounted for use of belatacept in combination with tacrolimus, transplant center effects, and differing approaches to matching. CONCLUSIONS: Belatacept appears to have similar longitudinal risk of mortality and allograft failure compared with tacrolimus-based regimens. These data are encouraging but require confirmation in prospective randomized controlled trials.