Brittany A. Shelton

Center-Level Experience and Kidney Transplant Outcomes in HIV-Infected Recipients

Excellent outcomes among HIV+ kidney transplant (KT) recipients have been reported by the NIH consortium, but it is unclear if experience with HIV+ KT is required to achieve these outcomes. We studied associations between experience measures and outcomes in 499 HIV+ recipients (SRTR data 2004–2011). Experience measures examined included: (1) center‐level participation in the NIH consortium; (2) KT experiential learning curve; and (3) transplant era (2004–2007 vs. 2008–2011). There was no difference in outcomes among centers early in their experience (first 5 HIV+ KT) compared to centers having performed >6 HIV+ KT (GS adjusted hazard ratio [aHR]: 1.05, 95% CI: 0.68–1.61, p = 0.82; PS aHR: 0.93; 95% CI: 0.56–1.53, p = 0.76), and participation in the NIH‐study was not associated with any better outcomes (GS aHR: 1.08, 95% CI: 0.71–1.65, p = 0.71; PS aHR: 1.13; 95% CI: 0.68–1.89, p = 0.63). Transplant era was strongly associated with outcomes; HIV+ KTs performed in 2008–2011 had 38% lower risk of graft loss (aHR: 0.62; 95% CI: 0.42–0.92, p = 0.02) and 41% lower risk of death (aHR: 0.59; 95% CI: 0.39–0.90, p = 0.01) than that in 2004–2007. Outcomes after HIV+ KT have improved over time, but center‐level experience or consortium participation is not necessary to achieve excellent outcomes, supporting continued expansion of HIV+ KT in the US.

Access to Kidney Transplantation among HIV-Infected Waitlist Candidates

BACKGROUND AND OBJECTIVES Kidney transplantation among HIV-infected patients with ESRD confers a significant survival benefit over remaining on dialysis. Given the high mortality burden associated with dialysis, understanding access to kidney transplantation after waitlisting among HIV+ candidates is warranted. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data from the Scientific Registry of Transplant Recipients were linked to Intercontinental Marketing Statistics pharmacy fills (January 1, 2001 to October 1, 2012) so that we could identify and study 1636 HIV+ (defined as having filled one or more antiretroviral medications unique to HIV treatment) and 72,297 HIV- kidney transplantation candidates. RESULTS HIV+ waiting list candidates were more often young (<50 years old: 62.7% versus 37.6%; P<0.001), were more often men (75.2% versus 59.3%; P<0.001), were more often black (73.6% versus 27.9%; P<0.001), had longer time on dialysis (years: 2.5 versus 0.8; P<0.001), were more often coinfected with hepatitis C virus (9.0% versus 3.9%; P<0.001), and were less likely to remain active on the waiting list (37.7% versus 49.4%; P<0.001). Waitlist mortality among HIV+ candidates was similar compared with HIV- candidates (adjusted hazard ratio, 1.03; 95% confidence interval, 0.89 to 1.20; P=0.67). In contrast, likelihood of living donor kidney transplantation was 47% lower (adjusted hazard ratio, 0.53; 95% confidence interval, 0.44 to 0.64; P<0.001), and there was a trend toward lower likelihood of deceased donor kidney transplantation (adjusted hazard ratio, 0.87; 95% confidence interval, 0.74 to 1.01; P=0.07) compared with in HIV- candidates. CONCLUSIONS Our findings highlight the need for additional study to better understand disparities in access to kidney transplantation, particularly living donor kidney transplantation, among HIV+ kidney waitlist candidates.

Impact of Protease Inhibitor–Based Anti‐Retroviral Therapy on Outcomes for HIV+ Kidney Transplant Recipients

Excellent outcomes have been demonstrated among select HIV‐positive kidney transplant (KT) recipients with well‐controlled infection, but to date, no national study has explored outcomes among HIV+ KT recipients by antiretroviral therapy (ART) regimen. Intercontinental Marketing Services (IMS) pharmacy fills (1/1/01–10/1/12) were linked with Scientific Registry of Transplant Recipients (SRTR) data. A total of 332 recipients with pre‐ and posttransplantation fills were characterized by ART at the time of transplantation as protease inhibitor (PI) or non–PI‐based ART (88 PI vs. 244 non‐PI). Cox proportional hazards models were adjusted for recipient and donor characteristics. Comparing recipients by ART regimen, there were no significant differences in age, race, or HCV status. Recipients on PI‐based regimens were significantly more likely to have an Estimated Post Transplant Survival (EPTS) score of >20% (70.9% vs. 56.3%, p = 0.02) than those on non‐PI regimens. On adjusted analyses, PI‐based regimens were associated with a 1.8‐fold increased risk of allograft loss (adjusted hazard ratio [aHR] 1.84, 95% confidence interval [CI] 1.22–2.77, p = 0.003), with the greatest risk observed in the first posttransplantation year (aHR 4.48, 95% CI 1.75–11.48, p = 0.002), and a 1.9‐fold increased risk of death as compared to non‐PI regimens (aHR 1.91, 95% CI 1.02–3.59, p = 0.05). These results suggest that whenever possible, recipients should be converted to a non‐PI regimen prior to kidney transplantation.

Effect of kidney donor hepatitis C virus serostatus on renal transplant recipient and allograft outcomes

Abstract Background Hepatitis C virus (HCV) infection is common in dialysis patients and renal transplant recipients and has been associated with diminished patient and allograft survival. HCV-positive (HCV+) kidneys have been used in HCV-positive (HCV+) recipients as a means of facilitating transplantation and expanding the organ donor pool; however, the effect of donor HCV serostatus in the modern era is unknown. Methods Using national transplant registry data, we created a propensity score–matched cohort of HCV+ recipients who received HCV-positive donor kidneys compared to those transplanted with HCV-negative kidneys. Results Transplantation with an HCV+ kidney was associated with an increased risk of death {hazard ratio [HR] 1.43 [95% confidence interval (CI) 1.18–1.76]; P < 0.001} and allograft loss [HR 1.39 (95% CI 1.16–1.67); P < 0.001] compared with their propensity score–matched counterparts. However, HCV+ kidneys were not associated with an increased risk of acute rejection [odds ratio 1.16 (95% CI 0.84–1.61); P = 0.35]. Conclusions While use of HCV+ donor kidneys can shorten the wait for renal transplantation and maximize organ utility for all candidates on the waiting list, potential recipients should be counseled about the increased risks associated with HCV+ kidney.

Survival Benefit of Kidney Transplantation in Hiv-infected Patients

Objective: To determine the survival benefit of kidney transplantation in human immunodeficiency virus (HIV)-infected patients with end-stage renal disease (ESRD). Summary Background Data: Although kidney transplantation (KT) has emerged as a viable option for select HIV-infected patients, concerns have been raised that risks of KT in HIV-infected patients are higher than those in their HIV-negative counterparts. Despite these increased risks, KT may provide survival benefit for the HIV-infected patient with ESRD, yet this important clinical question remains unanswered. Methods: Data from the Scientific Registry of Transplant Recipients were linked to IMS pharmacy fills (January 1, 2001 to October 1, 2012) to identify and study 1431 HIV-infected KT candidates from the first point of active status on the waiting list. Time-dependent Cox regression was used to establish a counterfactual framework for estimating survival benefit of KT. Results: Adjusted relative risk (aRR) of mortality at 5 years was 79% lower after KT compared with dialysis (aRR 0.21; 95% CI 0.10–0.42; P <0.001), and statistically significant survival benefit was achieved by 194 days of KT. Among patients coinfected with hepatitis C, aRR of mortality at 5 years was 91% lower after KT compared with dialysis (aRR 0.09; 95% CI 0.02–0.46; P < 0.004); however, statistically significant survival benefit was not achieved until 392 days after KT. Conclusions: Evidence suggests that for HIV-infected ESRD patients, KT is associated with a significant survival benefit compared with remaining on dialysis.

Kidney transplantation and waitlist mortality rates among candidates registered as willing to accept a hepatitis C infected kidney

HCV‐infected (HCV+) ESRD patients derive significant survival benefit from kidney transplantation (KT) over remaining on dialysis. Given high mortality rates on dialysis and the unique ability to accept HCV+ and HCV‐ donor kidneys, understanding their access to KT is essential.

Lymphocyte-depleting induction therapy lowers the risk of acute rejection in African American pediatric kidney transplant recipients.

The use of lymphocyte‐depleting induction immunosuppression has been associated with a reduction in risk of AR after KT among adult recipients, particularly among high‐risk subgroups such as AAs. However, data on induction regimen and AR risk are lacking among pediatric KT recipients. We examined outcomes among 7884 first‐time pediatric KT recipients using SRTR data (2000‐2014). Characteristics were compared across race using Wilcoxon rank‐sum tests for continuous and chi‐square tests for categorical variables. Risk of AR was estimated using modified Poisson regression, stratified by recipient race, adjusting for recipient age, gender, BMI, primary diagnosis, number of HLA mismatches, maintenance immunosuppression, and donor type. Risk of AR within 1 year was lower in AA recipients receiving lymphocyte‐depleting induction (ATG or alemtuzumab; RR, 0.66; 95% CI, 0.52‐0.83 P < .001) compared to AA recipients receiving anti‐IL‐2 receptor antibody induction. This difference was not seen in non‐AA recipients receiving lymphocyte‐depleting induction (RR, 0.93; 95% CI, 0.81‐1.06, P = .26) compared to IL‐2 induction. These findings support a role for lymphocyte‐depleting induction agents in AA pediatric patients undergoing KT and continued use of IL‐2 inhibitor induction in non‐AA pediatric KT recipients.

Apolipoprotein L1 and Chronic Kidney Disease Risk in Young Potential Living Kidney Donors

Objective:The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. Summary of Background Data:Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs). Methods:We identified a cohort of young adults (18–30 years) with no absolute contraindication to kidney donation from the longitudinal cohort study Coronary Artery Risk Development in Young Adults. Risk associations for CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) were identified and assigned weighted points to calculate risk scores. Results:A total of 3438 healthy adults were identified [mean age 24.8 years; 48.3% AA; median follow-up 24.9 years (interquartile range: 24.5–25.2)]. For 18-year olds, 25-year projected CKD risk varied by ethnicity and sex even without baseline clinical and genetic abnormalities; risk was 0.30% for European American (EA) women, 0.52% for EA men, 0.52% for AA women, 0.90% for AA men. Among 18-year-old AAs with apolipoprotein L1 gene (APOL1) renal-risk variants without baseline abnormalities, 25-year risk significantly increased: 1.46% for women and 2.53% for men; among those with 2 APOL1 renal-risk variants and baseline abnormalities, 25-year risk was higher: 2.53% to 6.23% for women and 4.35% to 10.58% for men. Conclusions:Young AAs were at highest risk for CKD, and APOL1 renal-risk variants drove some of this risk. Understanding the genetic profile of young AA potential living kidney donors in the context of baseline health characteristics may help to inform candidate selection and counseling.

Decreasing deceased donor transplant rates among children (≤6 years) under the new kidney allocation system

The Kidney Allocation System (KAS) was implemented in December 2014 with unknown impact on the pediatric waitlist. To understand the effect of KAS on pediatric registrants, deceased donor kidney transplant (DDKT) rate was assessed using interrupted time series analysis and time‐to‐event analysis. Two allocation eras were defined with an intermediary washout period: Era 1 (01/01/2013‐09/01/2014), Era 2 (09/01/2014‐03/01/2015), and Era 3(03/01/2015‐03/01/2017). When using Cox proportional hazards, there was no significant association between allocation era and DDKT likelihood as compared to Era 1 (Era 3: aHR: 1.07, 95% CI: 0.97‐1.18, P = .17). However, this was not consistent across all subgroups. Specifically, while highly sensitized pediatric registrants were consistently less likely to be transplanted than their less sensitized counterparts, this disparity was attenuated in Era 3 (Era 1 aHR: 0.04, 95%CI: 0.01‐0.14, P < .001; Era 3 aHR: 0.33, 95% CI: 0.21‐0.53, P < .001) whereas the youngest registrants aged 0‐6 experienced a 21% decrease in DDKT likelihood in Era 3 as compared to Era 1 (aHR: 0.79, 95% CI: 0.64‐0.98, P = .03). Thus, while overall DDKT likelihood remained stable with the introduction of KAS, registrants ≤ 6 years of age were disadvantaged, warranting further study to ensure equitable access to transplantation.

Identification of Optimal Donor-Recipient Combinations Among Human Immunodeficiency Virus (HIV)-Positive Kidney Transplant Recipients.

For some patient subgroups, human immunodeficiency virus (HIV) infection has been associated with worse outcomes after kidney transplantation (KT); potentially modifiable factors may be responsible. The study goal was to identify factors that predict a higher risk of graft loss among HIV‐positive KT recipients compared with a similar transplant among HIV‐negative recipients. In this study, 82 762 deceased donor KT recipients (HIV positive: 526; HIV negative: 82 236) reported to the Scientific Registry of Transplant Recipients (SRTR) (2001–2013) were studied by interaction term analysis. Compared to HIV‐negative recipients, the hepatitis C virus (HCV) amplified risk 2.72‐fold among HIV‐positive KT recipients (adjusted hazard ratio [aHR]: 2.72, 95% confidence interval [CI]: 1.75–4.22, p < 0.001). Forty‐three percent of the excess risk was attributable to the interaction between HIV and HCV (attributable proportion of risk due to the interaction [AP]: 0.43, 95% CI: 0.23–0.63, p = 0.02). Among HIV‐positive recipients with more than three HLA mismatches (MMs), risk was amplified 1.80‐fold compared to HIV‐negative (aHR: 1.80, 95% CI: 1.31–2.47, p < 0.001); 42% of the excess risk was attributable to the interaction between HIV and more than three HLA MMs (AP: 0.42, 95% CI: 0.24–0.60, p = 0.01). High‐HIV‐risk (HIV‐positive/HCV‐positive HLAwith more than three MMs) recipients had a 3.86‐fold increased risk compared to low‐HIV‐risk (HIV‐positive/HCV‐negative HLA with three or fewer MMs)) recipients (aHR: 3.86, 95% CI: 2.37–6.30, p < 0.001). Avoidance of more than three HLA MMs in HIV‐positive KT recipients, particularly among coinfected patients, may mitigate the increased risk of graft loss associated with HIV infection.