Faculty Bibliography

BACKGROUND:In response to recent studies, a better understanding of the risks of renal complications among African American and biologically related living kidney donors is needed. METHODS:We examined a database linking U.S. registry identifiers for living kidney donors (1987-2007) to billing claims from a private health insurer (2000-2007 claims) to identify renal condition diagnoses categorized by International Classification of Diseases 9th Revision coding. Cox regression with left and right censoring was used to estimate cumulative incidence of diagnoses after donation and associations (adjusted hazards ratios, aHR) with donor traits. RESULTS:Among 4650 living donors, 13.1% were African American and 76.3% were white; 76.1% were first-degree relatives of their recipient. By 7 years post-donation, after adjustment for age and sex, greater proportions of African American compared with white donors had renal condition diagnoses: chronic kidney disease (12.6% vs 5.6%; aHR, 2.32; 95% confidence interval [95% CI], 1.48-3.62), proteinuria (5.7% vs 2.6%; aHR, 2.27; 95% CI, 1.32-3.89), nephrotic syndrome (1.3% vs 0.1%; aHR, 15.7; 95% CI, 2.97-83.0), and any renal condition (14.9% vs 9.0%; aHR, 1.72; 95% CI, 1.23-2.41). Although first-degree biological relationship to the recipient was not associated with renal risk, associations of African American race persisted for these conditions and included unspecified renal failure and reported disorders of kidney dysfunction after adjustment for biological donor-recipient relationship. CONCLUSIONS:African Americans more commonly develop renal conditions after living kidney donation, independent of donor-recipient relationship. Continued research is needed to improve risk stratification for renal outcomes among African American living donors.

Concerns have been raised that optimized redistricting of liver allocation areas might have the unintended result of shifting livers from better-performing to poorer-performing organ procurement organizations (OPOs). We used liver simulated allocation modeling to simulate a 5-year period of liver sharing within either 4 or 8 optimized districts. We investigated whether each OPO's net liver import under redistricting would be correlated with 2 OPO performance metrics (observed to expected liver yield and liver donor conversion ratio), along with 2 other potential correlates (eligible deaths and incident listings above a Model for End-Stage Liver Disease score of 15). We found no evidence that livers would flow from better-performing OPOs to poorer-performing OPOs in either redistricting scenario. Instead, under these optimized redistricting plans, our simulations suggest that livers would flow from OPOs with more-than-expected eligible deaths toward those with fewer-than-expected eligible deaths and that livers would flow from OPOs with fewer-than-expected incident listings to those with more-than-expected incident listings; the latter is a pattern that is already established in the current allocation system. Redistricting liver distribution to reduce geographic inequity is expected to align liver allocation across the country with the distribution of supply and demand rather than transferring livers from better-performing OPOs to poorer-performing OPOs.

U.S. organ allocation policy sequesters livers from deceased donors within arbitrary geographic boundaries, frustrating the intent of those who wish to offer the livers to transplant candidates based on medical urgency. We used a zero-one integer program to partition 58 donor service areas into between four and eight sharing districts that minimize the disparity in liver availability among districts. Because the integer program necessarily suppressed clinically significant differences among patients and organs, we tested the optimized district maps with a discrete-event simulation tool that represents liver allocation at a per-person, per-organ level of detail. In April 2014, the liver committee of the Organ Procurement and Transplantation Network (OPTN) decided in a unanimous vote of 22-0-0 to write a policy proposal based on our eight-district and four-district maps. The OPTN board of directors could implement the policy after the proposal and public-comment period.Redistricting liver allocation would save hundreds of lives over the next five years and would attenuate the serious geographic inequity in liver transplant offers.

Life expectancy among HIV-infected (HIV+) individuals has improved dramatically with effective antiretroviral therapy. Consequently, chronic diseases such as end-stage liver and kidney disease are growing causes of morbidity and mortality. HIV+ individuals can have excellent outcomes after solid organ transplantation, and the need for transplantation in this population is increasing. However, there is a significant organ shortage, and HIV+ individuals experience higher mortality rates on transplant waitlists. In South Africa, the use of organs from HIV+ deceased donors (HIVDD) has been successful, but until recently federal law prohibited this practice in the United States. With the recognition that organs from HIVDD could fill a critical need, the HIV Organ Policy Equity (HOPE) Act was passed in November 2013, reversing the federal ban on the use of HIV+ donors for HIV+ recipients. In translating this policy into practice, the biologic risks of using HIV+ donors need to be carefully considered. In this mini-review, we explore relevant aspects of HIV virology, antiretroviral treatment, drug resistance, opportunistic infections and HIV-related organ dysfunction that are critical to a transplant team considering HIV-to-HIV transplantation.

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.

BACKGROUND: Patient-level risk factors for delayed graft function (DGF) have been well described. However, the Organ Procurement and Transplantation Network definition of DGF is based on dialysis in the first week, which is subject to center-level practice patterns. It remains unclear if there are center-level differences in DGF and if measurable center characteristics can explain these differences. METHODS: Using the 2003 to 2012 Scientific Registry of Transplant Recipients data, we developed a hierarchical (multilevel) model to determine the association between center characteristics and DGF incidence after adjusting for known patient risk factors and to quantify residual variability across centers after adjustment for these factors. RESULTS: Of 82,143 deceased donor kidney transplant recipients, 27.0% developed DGF, with a range across centers of 3.2% to 63.3%. A center's proportion of preemptive transplants (odds ratio [OR], 0.83; per 5% increment; 95% confidence interval [95% CI], 0.74-;0.93; P = 0.001) and kidneys with longer than 30 hr of cold ischemia time (CIT) (OR, 0.95; per 5% increment; 95% CI, 0.92-;0.98; P = 0.001) were associated with less DGF. A center's proportion of donation after cardiac death donors (OR, 1.12; per 5% increment; 95% CI, 1.03-;1.17; P < 0.001) and imported kidneys (OR, 1.06; per 5% increment; 95% CI, 1.03-;1.10; P < 0.001) were associated with more DGF. After patient-level and center-level adjustments, only 41.8% of centers had DGF incidences consistent with the national median and 28.2% had incidences above the national median. CONCLUSION: Significant heterogeneity in DGF incidences across centers, even after adjusting for patient-level and center-level characteristics, calls into question the generalizability and validity of the current DGF definition. Enhanced understanding of center-level variability and improving the definition of DGF accordingly may improve DGF's utility in clinical care and as a surrogate endpoint in clinical trials.

BACKGROUND:Induction immunosuppression is a mainstay of rejection prevention after transplantation. Studies have suggested a connection between antibody induction agents and cancer development, potentially limiting important immunosuppression protocols. METHODS:We used a linkage of U.S. transplantation data and cancer registries to explore the relationship between induction and cancer after transplantation. A total of 111,857 kidney recipients (1987-2009) in the Transplant Cancer Match Study, which links the Scientific Registry for Transplant Recipients and U.S. Cancer Registries, were included. Poisson regression models were used to estimate adjusted incidence rate ratios (aIRR) of non-Hodgkin lymphoma (NHL) and other cancers with increased incidence after transplantation (lung, colorectal, kidney, and thyroid cancers, plus melanoma). RESULTS:Two thousand seven hundred sixty-three cancers of interest were identified. Muromonab-CD3 was associated with increased NHL (aIRR, 1.37; 95% CI, 1.06-1.76). Alemtuzumab was associated with increased NHL (aIRR, 1.79; 95% CI, 1.02-3.14), colorectal cancer (aIRR, 2.46; 95% CI, 1.03-5.91), and thyroid cancer (aIRR, 3.37; 95% CI, 1.55-7.33). Polyclonal induction was associated with increased melanoma (aIRR, 1.50; 95% CI, 1.06-2.14). CONCLUSION/CONCLUSIONS:Our findings highlight the relative safety with regard to cancer risk of the most common induction therapies, the need for surveillance of patients treated with alemtuzumab, and the possible role for increased melanoma screening for those patients treated with polyclonal anti-T-cell induction.

IMPORTANCE/OBJECTIVE:Based on evidence of survival benefit when initiating hemodialysis (HD) via arteriovenous fistula (AVF) or arteriovenous graft (AVG) vs hemodialysis catheter (HC), the National Kidney Foundation-Kidney Disease Outcomes Quality Initiative published practice guidelines in 1997 recommending 50% or greater AVF rates in incident HD patients. A decade after, lapses exist and the impact on HD outcomes is uncertain. OBJECTIVE:To assess the achievement of the practice goals for incident vascular access and the effects on HD outcomes. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This retrospective cohort study was conducted using the US Renal Data System. All patients with end-stage renal disease in the United States without prior renal replacement therapy who had incident vascular access for HD created between January 1, 2006, and December 31, 2010 (N = 510 000) were included. MAIN OUTCOMES AND MEASURES/METHODS:Incident vascular access use rates and mortality. Relative mortality was quantified using multivariable Cox proportional hazard models. Coarsened exact matching and propensity score-matching techniques were used to better account for confounding by indication. RESULTS:Of 510 000 patients included in this study, 82.6% initiated HD via HC, 14.0% via AVF, and 3.4% via AVG. Arteriovenous fistula use increased only minimally, from 12.2% in 2006 to 15.0% in 2010. Patients initiating HD with AVF had 35% lower mortality than those with HC (adjusted hazard ratio, 0.65; 95% CI, 0.64-0.66; P < .001). Those initiating HD with AVF had 23% lower mortality than those initiating with an HC while awaiting maturation of an AVF (adjusted hazard ratio, 0.77; 95% CI, 0.76-0.79; P < .001). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Current incident AVF practice falls exceedingly short years after recommendations were made in 1997. The impact of this shortcoming on mortality for patients with end-stage renal disease is enormous. Functioning permanent access at initiation of HD confers lower mortality even compared with patients temporized with an HC while awaiting maturation of permanent access. A change of current policies and structured multidisciplinary efforts are required to establish matured fistulae prior to HD to ameliorate this deficit in delivering care.