Faculty Bibliography

We examined integrated national transplant registry, pharmacy fill, and medical claims data for Medicare-insured kidney transplant recipients in 2000-2011 (n = 45 164) from the United States Renal Data System to assess the efficacy and safety endpoints associated with seven early (first 90 days) immunosuppression (ISx) regimens. Risks of clinical complications over 3 years according to IS regimens were assessed with multivariate regression analysis, including the adjustment for covariates and propensity for receipt of a nonreference ISx regimen. Compared with the reference ISx (thymoglobulin induction with tacrolimus, mycophenolate, and prednisone maintenance), sirolimus-based ISx was associated with significantly higher three-year risks of pneumonia (adjusted hazard ratio, aHR 1.45; P < 0.0001), sepsis (aHR 1.40; P < 0.0001), diabetes (aHR 1.21; P < 0.0001), acute rejection (AR; adjusted odds ratio, aOR 1.33; P < 0.0001), graft failure (aHR 1.78; P < 0.0001), and patient death (aHR 1.40; P < 0.0001), but reduced skin cancer risk (aHR 0.71; P < 0.001). Cyclosporine-based IS was associated with increased risks of pneumonia (aHR 1.17; P < 0.001), sepsis (aHR 1.16; P < 0.001), AR (aOR 1.43; P < 0.001), and graft failure (aHR 1.39; P < 0.001), but less diabetes (aHR 0.83; P < 0.001). Steroid-free ISx was associated with the reduced risk of pneumonia (aHR 0.89; P = 0.002), sepsis (aHR 0.80; P < 0.001), and diabetes (aHR 0.77; P < 0.001), but higher graft failure (aHR 1.35; P < 0.001). Impacts of ISx over time warrant further study to better guide ISx tailoring to balance the efficacy and morbidity.

Earlier studies reported inferior outcomes among black compared with white kidney transplant (KT) recipients. We examined whether this disparity improved in recent decades. Using the Scientific Registry of Transplant Recipients and Cox regression models, we compared all-cause graft loss among 63,910 black and 145,482 white adults who received a first-time live donor KT (LDKT) or deceased donor KT (DDKT) in 1990-2012. Over this period, 5-year graft loss after DDKT improved from 51.4% to 30.6% for blacks and from 37.3% to 25.0% for whites; 5-year graft loss after LDKT improved from 37.4% to 22.2% for blacks and from 20.8% to 13.9% for whites. Among DDKT recipients in the earliest cohort, blacks were 39% more likely than whites to experience 5-year graft loss (adjusted hazard ratio [aHR], 1.39; 95% confidence interval [95% CI], 1.32 to 1.47; P<0.001), but this disparity narrowed in the most recent cohort (aHR, 1.10; 95% CI, 1.03 to 1.18; P=0.01). Among LDKT recipients in the earliest cohort, blacks were 53% more likely than whites to experience 5-year graft loss (aHR, 1.53; 95% CI, 1.27 to 1.83; P<0.001), but this disparity also narrowed in the most recent cohort (aHR, 1.37; 95% CI, 1.17 to 1.61; P<0.001). Analyses revealed no statistically significant differences in 1-year or 3-year graft loss after LDKT or DDKT in the most recent cohorts. Our findings of reduced disparities over the last 22 years driven by more markedly improved outcomes for blacks may encourage nephrologists and patients to aggressively promote access to transplantation in the black community.

The Kidney Allocation System (KAS), a major change to deceased donor kidney allocation, was implemented in December 2014. Goals of KAS included directing the highest-quality organs to younger/healthier recipients and increasing access to deceased donor kidney transplantation (DDKT) for highly sensitized patients and racial/ethnic minorities. Using national registry data, we compared kidney distribution, DDKT rates for waitlist registrants, and recipient characteristics between January 1, 2013, and December 3, 2014 (pre-KAS) with those between December 4, 2014, and August 31, 2015 (post-KAS). Regional imports increased from 8.8% pre-KAS to 12.5% post-KAS; national imports increased from 12.7% pre-KAS to 19.1% post-KAS (P<0.001). The proportion of recipients >30 years older than their donor decreased from 19.4% to 15.0% (P<0.001). The proportion of recipients with calculated panel-reactive antibody =100 increased from 1.0% to 10.3% (P<0.001). Overall DDKT rate did not change as modeled using exponential regression adjusting for candidate characteristics (P=0.07). However, DDKT rate (incidence rate ratio, 95% confidence interval) increased for black (1.19; 1.13 to 1.25) and Hispanic (1.13; 1.05 to 1.20) candidates and for candidates aged 18-40 (1.47; 1.38 to 1.57), but declined for candidates aged >50 (0.93; 0.87 to 0.98 for aged 51-60 and 0.90; 0.85 to 0.96 for aged >70). Delayed graft function in transplant recipients increased from 24.8% pre-KAS to 29.9% post-KAS (P<0.001). Thus, in the first 9 months under KAS, access to DDKT improved for minorities, younger candidates, and highly sensitized patients, but declined for older candidates. Delayed graft function increased substantially, possibly suggesting poorer long-term outcomes.

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.

The HIV Organ Policy Equity (HOPE) Act now allows transplantation of organs from HIV-positive living and deceased donors to HIV-positive individuals with end-stage organ disease in the United States. Although clinical experience with such transplants is limited to a small number of deceased-donor kidney transplants from HIV-positive to HIV-positive persons in South Africa, unprecedented HIV-positive-to-HIV-positive liver transplantations and living-donor kidney transplantations are also now on the horizon. Initially, all HIV-positive-to-HIV-positive transplantations will occur under research protocols with safeguards and criteria mandated by the National Institutes of Health. Nevertheless, this historic change brings ethical opportunities and challenges. For HIV-positive individuals needing an organ transplant, issues of access, risk, and consent must be considered. For potential HIV-positive donors, there are additional ethical challenges of privacy, fairness, and the right to donate. Careful consideration of the ethical issues involved is critical to the safe and appropriate evaluation of this novel approach to transplantation.

Since March 26, 2012, the Kidney Donor Profile Index (KDPI) has been provided with all deceased-donor kidney offers, with the goal of improving the expanded criteria donor (ECD) indicator. Although an improved risk index may facilitate identification and transplantation of marginal yet viable kidneys, a granular percentile system may reduce provider-patient communication flexibility, paradoxically leading to more discards ("labeling effect"). We studied the discard rates of the kidneys recovered for transplantation between March 26, 2010 and March 25, 2012 ("ECD era," N = 28 636) and March 26, 2012 and March 25, 2014 ("KDPI era," N = 29 021) using Scientific Registry of Transplant Recipients (SRTR) data. There was no significant change in discard rate from ECD era (18.1%) to KDPI era (18.3%) among the entire population (adjusted odds ratio [aOR] = 0.97 1.041.10 , p = 0.3), or in any KDPI stratum. However, among kidneys in which ECD and KDPI indicators were discordant, "high risk" standard criteria donor (SCD) kidneys (with KDPI > 85) were at increased risk of discard in the KDPI era (aOR = 1.07 1.421.89 , p = 0.02). Yet, recipients of these kidneys were at much lower risk of death (adjusted Risk Ratio [aRR] = 0.56 0.770.94 at 2 years posttransplant) compared to those remaining on dialysis waiting for low-KDPI kidneys. Our findings suggest that there might be an unexpected, harmful labeling effect of reporting a high KDPI for SCD kidneys, without the expected advantage of providing a more granular risk index.

Choosing between multiple living kidney donors, or evaluating offers in kidney paired donation, can be challenging because no metric currently exists for living donor quality. Furthermore, some deceased donor (DD) kidneys can result in better outcomes than some living donor kidneys, yet there is no way to compare them on the same scale. To better inform clinical decision-making, we created a living kidney donor profile index (LKDPI) on the same scale as the DD KDPI, using Cox regression and adjusting for recipient characteristics. Donor age over 50 (hazard ratio [HR] per 10 years = 1.15 1.241.33 ), elevated BMI (HR per 10 units = 1.01 1.091.16 ), African-American race (HR = 1.15 1.251.37 ), cigarette use (HR = 1.09 1.161.23 ), as well as ABO incompatibility (HR = 1.03 1.271.58 ), HLA B (HR = 1.03 1.081.14 ) mismatches, and DR (HR = 1.04 1.091.15 ) mismatches were associated with greater risk of graft loss after living donor transplantation (all p < 0.05). Median (interquartile range) LKDPI score was 13 (1-27); 24.2% of donors had LKDPI < 0 (less risk than any DD kidney), and 4.4% of donors had LKDPI > 50 (more risk than the median DD kidney). The LKDPI is a useful tool for comparing living donor kidneys to each other and to deceased donor kidneys.

BACKGROUND: Kidney donors can develop end-stage renal disease (ESRD) after donation, but the outcomes of those who do remain poorly characterized. METHODS: Using United States Renal Data System and Scientific Registry for Transplant Research data, we compared access to kidney transplantation (KT), time from ESRD to listing, time from listing to KT, and post-KT graft failure and death between donors and matched nondonors with ESRD. RESULTS: Among 99 donors between April 1994 and November 2011 who developed ESRD, 78 initially received dialysis (of whom 37 listed for KT, 2 received live donor KT without listing, and 39 never listed for or received a KT), 20 listed preemptively (of whom 19 were subsequently transplanted), and 1 received a preemptive live donor KT without listing or ever receiving dialysis. Donors were listed earlier (median time to listing, 17 months vs 120 for nondonors; P < 0.001), received KT earlier (median waiting time, 2.8 months vs 21.5 for nondonors; P < 0.001), and received 13% live donor, 87% standard criteria, and 0% expanded criteria deceased donor KT (39%, 50%, and 11% in nondonors). Post-KT graft (adjusted hazard ratio, 1.9; 95% confidence interval, 0.9 to 4.1; P = 0.1) and patient (adjusted hazard ratio, 0.7; 95% confidence interval, 0.2 to 2.4; P = 0.5) survival were comparable in donors and nondonors. CONCLUSIONS: Our finding that 39 of 99 donors who developed ESRD never listed for a transplant warrants further study to ascertain why these donors with ESRD never gained access to the waiting list.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.

BACKGROUND: Recent evidence suggests that living kidney donors are at an increased risk of end-stage renal disease. However, predicting which donors will have renal dysfunction remains challenging, particularly among those with no clinical evidence of disease at the time of donation. Although renal biopsies are not routinely performed as part of the donor evaluation process, they may yield valuable information that improves the ability to predict renal function in donors. METHODS: We used implantation protocol biopsies to evaluate the association between histological abnormalities in the donated kidney and postdonation renal function (estimated glomerular filtration rate, eGFR) of the remaining kidney in living kidney donors. Longitudinal analysis using mixed-effects linear regression was used to account for multiple eGFR measures per donor. RESULTS: Among 310 donors between 1997 and 2012, median (IQR) follow-up was 6.2 (2.5-8.7; maximum 14.0) years. In this cohort, the overall prevalence of histological abnormalities was 65.8% (19.7% abnormal glomerulosclerosis, 23.9% abnormal interstitial fibrosis and tubular atrophy (IFTA), 4.8% abnormal mesangial matrix increase, 32.0% abnormal arteriolar hyalinosis, and 32.9% abnormal vascular intimal thickening). IFTA was associated with a 5-mL/min/1.73 m decrease of postdonation eGFR after adjusting for donor age at donation, sex, race, preoperative systolic blood pressure, preoperative eGFR, and time since donation (P < 0.01). CONCLUSIONS: In this single-center study, among healthy individuals cleared for living donation, IFTA was associated with decreased postdonation eGFR, whereas no other subclinical histological abnormalities provided additional information.