Faculty Bibliography

BACKGROUND:Living kidney donors have an increased risk of end-stage renal disease, with hypertension and diabetes as the predominant causes. In this study, we sought to better understand the timeline when these diseases occur, focusing on the early postdonation period. METHODS:We studied 41 260 living kidney donors in the United States between 2008 and 2014 from the Scientific Registry of Transplant Recipients and modeled incidence rates and risk factors for hypertension and diabetes. RESULTS:At 6 months, 1 year, and 2 years postdonation, there were 74, 162, and 310 cases, respectively, of hypertension per 10 000 donors. Donors who were older (per 10 y, adjusted incidence rate ratio [aIRR], 1.40; 95% confidence interval [CI], 1.29-1.51), male (aIRR, 1.31; 95% CI, 1.14-1.50), had higher body mass index (per 5 units, aIRR, 1.29; 95% CI, 1.17-1.43), and were related to their recipient (first-degree relative: aIRR, 1.28; 95% CI, 1.08-1.52; spouse: aIRR, 1.34; 95% CI, 1.08-1.66) were more likely to develop hypertension, whereas donors who were Hispanic/Latino were less likely (aIRR, 0.71; 95% CI, 0.55-0.93). At 6 months, 1 year, and 2 years, there were 2, 6, and 15 cases of diabetes per 10 000 donors. Donors who were older (per 10 y: aIRR, 1.42; 95% CI, 1.11-1.82), had higher body mass index (per 5 units: aIRR, 1.52; 95% CI, 1.04-2.21), and were Hispanic/Latino (aIRR, 2.45; 95% CI, 1.14-5.26) were more likely to develop diabetes. CONCLUSIONS:In this national study, new-onset diabetes was rare, but 3% of donors developed hypertension within 2 years of nephrectomy. These findings reaffirm that disease pathways for kidney failure differ by donor phenotype and estimate the population most at-risk for later kidney failure.

Prior studies have shown that beginning hemodialysis (HD) with a hemodialysis catheter (HC) is associated with worse mortality than with an arteriovenous fistula (AVF) or arteriovenous graft (AVG). We hypothesized that transplant waitlisting would modify the effect of HD access on mortality, given waitlist candidates' more robust health status. Using the US Renal Data System, we studied patients with incident ESRD who initiated HD between 2010 and 2015 with an AVF, AVG, or HC. We used Cox regression including an interaction term for HD access and waitlist status. There were 587,607 patients that initiated HD, of whom 82,379 (14.0%) were waitlisted for transplantation. Only 26,264 (4.5%) were transplanted. Among patients not listed, those with an AVF had a 34% lower mortality compared to HC [adjusted hazard ratio (aHR) 0.66, 95% confidence interval (CI) 0.65-0.67] while those with an AVG had a 21% lower mortality compared to HC (aHR 0.79, 95% CI 0.77-0.81). Transplant waitlisting attenuated the association between hemodialysis access type and mortality (interaction p < 0.001 for both AVF and AVG vs. HC). Among patients on the waitlist, those with an AVF had a 12% lower mortality compared to HC (aHR 0.88, 95% CI 0.84-0.93), while those with an AVG had no difference in mortality (aHR 0.95, 95% CI 0.84-1.08). While all patients benefit from AVF or AVG over HC, the benefit was attenuated in waitlisted patients. Efforts to improve health status and access to healthcare for non-waitlisted ESRD patients might decrease HD-associated mortality and improve rates of AVF and AVG placement.

Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell-depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all-cause mortality, CVE-related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL-2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92-1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89-1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00-1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all-cause or CVE-related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.

The impact of donor quality on post-kidney transplant (KT) survival may vary by candidate condition. Characterizing this variation would increase access to KT without sacrificing outcomes. We developed a tool to estimate post-KT survival for combinations of donor quality and candidate condition. We studied deceased donor KT recipients (n = 120 818) and waitlisted candidates (n = 376 272) between 2005 and 2016 by using the Scientific Registry of Transplant Recipients. Donor quality and candidate condition were measured by using the Kidney Donor Profile Index (KDPI) and the Estimated Post Transplant Survival (EPTS) score. We estimated 5-year post-KT survival based on combinations of KDPI and EPTS score using random forest algorithms and waitlist survival by EPTS score using Weibull regressions. Survival benefit was defined as absolute reduction in mortality risk with KT. For candidates with an EPTS score of 80, 5-year waitlist survival was 47.6%, and 5-year post-KT survival was 78.9% after receiving kidneys with a KDPI of 20 and was 70.7% after receiving kidneys with a KDPI of 80. The impact of KDPI on survival benefit varied greatly by EPTS score. For candidates with low EPTS scores (eg, <40), the KDPI had limited impact on survival benefit. For candidates with middle or high EPTS scores (eg, >40), survival benefit decreased with higher KDPI but was still substantial even with a KDPI of 100 (>16 percentage points). Our prediction tool (www.transplantmodels.com/kdpi-epts) can support individualized decision-making on kidney offers in clinical practice.

AIM/OBJECTIVE:There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear. METHODS:Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight. RESULTS:Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03). CONCLUSION/CONCLUSIONS:Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.

A recent study reported that kidney transplant recipients of offspring living donors had higher graft loss and mortality. This seemed counterintuitive, given the excellent HLA matching and younger age of offspring donors; we were concerned about residual confounding and other study design issues. We used Scientific Registry of Transplant Recipients data 2001-2016 to evaluate death-censored graft failure (DCGF) and mortality for recipients of offspring versus nonoffspring living donor kidneys, using Cox regression models with interaction terms. Recipients of offspring kidneys had lower DCGF than recipients of nonoffspring kidneys (15-year cumulative incidence 21.2% vs 26.1%, P < .001). This association remained after adjustment for recipient and transplant factors (adjusted hazard ratio [aHR] = _0.73 0.77_0.82 , P < .001), and was attenuated among African American donors (aHR _0.77 0.85_0.95 ; interaction: P = .01) and female recipients (aHR _0.77 0.84_0.91 , P < .001). Although offspring kidney recipients had higher mortality (15-year mortality 56.4% vs 37.2%, P < .001), this largely disappeared with adjustment for recipient age alone (aHR = _1.02 1.06_1.10 , P = .002) and was nonsignificant after further adjustment for other recipient characteristics (aHR = _0.93 0.97_1.01 , P = .1). Kidneys from offspring donors provided lower graft failure and comparable mortality. An otherwise eligible donor should not be dismissed because they are the offspring of the recipient, and we encourage continued individualized counseling for potential donors.

BACKGROUND:The availability of direct-acting antiviral (DAA) therapy might have impacted use of hepatitis C virus (HCV)-infected (HCV+) deceased donor kidneys for transplantation. METHODS:We used 2005 to 2018 Scientific Registry of Transplant Recipients data to identify 18 936 candidates willing to accept HCV+ kidneys and 3348 HCV+ recipients of HCV+ kidneys. We compared willingness to accept, utilization, discard, and posttransplant outcomes associated with HCV+ kidneys between 2 treatment eras (interferon [IFN] era, January 1, 2005 to December 5, 2013 vs DAA era, December 6, 2013 to August 2, 2018). Models were adjusted for candidate, recipient, and donor factors where appropriate. RESULTS:In the DAA era, candidates were 2.2 times more likely to list as willing to accept HCV+ kidneys (adjusted odds ratio, 2.072.232.41; P < 0.001), and HCV+ recipients were 1.95 times more likely to have received an HCV+ kidney (adjusted odds ratio, 1.761.952.16; P < 0.001). Median Kidney Donor Profile Index of HCV+ kidneys decreased from 77 (interquartile range [IQR], 59-90) in 2005 to 53 (IQR, 40-67) in 2017. Kidney Donor Profile Index of HCV- kidneys remained unchanged from 45 (IQR, 21-74) to 47 (IQR, 24-73). After adjustment, HCV+ kidneys were 3.7 times more likely to be discarded than HCV- kidneys in the DAA era (adjusted relative rate, 3.363.674.02; P < 0.001); an increase from the IFN era (adjusted relative rate, 2.783.023.27; P < 0.001). HCV+ kidney use was concentrated within a subset of centers; 22.5% of centers performed 75% of all HCV+ kidney transplants in the DAA era. Mortality risk associated with HCV+ kidneys remained unchanged (aHR, 1.071.191.32 in both eras). CONCLUSIONS:Given the elevated risk of death on dialysis facing HCV+ candidates, improving quality of HCV+ kidneys, and DAA availability, broader utilization of HCV+ kidneys is warranted to improve access in this era of organ shortage.