Faculty Bibliography

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 m) 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.

The Kidney Allocation System fundamentally altered kidney allocation, causing a substantial increase in regional and national sharing that we hypothesized might impact geographic disparities. We measured geographic disparity in deceased donor kidney transplant (DDKT) rate under KAS (6/1/2015-12/1/2016), and compared that with pre-KAS (6/1/2013-12/3/2014). We modeled DSA-level DDKT rates with multilevel Poisson regression, adjusting for allocation factors under KAS. Using the model we calculated a novel, improved metric of geographic disparity: the median incidence rate ratio (MIRR) of transplant rate, a measure of DSA-level variation that accounts for patient casemix and is robust to outlier values. Under KAS, MIRR was _1.75 1.81_1.86 for adults, meaning that similar candidates across different DSAs have a median 1.81-fold difference in DDKT rate. The impact of geography was greater than the impact of factors emphasized by KAS: having an EPTS score ≤20% was associated with a 1.40-fold increase (IRR = _1.35 1.40_1.45 , P < .01) and a three-year dialysis vintage was associated with a 1.57-fold increase (IRR = _1.56 1.57_1.59 , P < .001) in transplant rate. For pediatric candidates, MIRR was even more pronounced, at _1.66 1.92_2.27 . There was no change in geographic disparities with KAS (P = .3). Despite extensive changes to kidney allocation under KAS, geography remains a primary determinant of access to DDKT.

Kidney paired donation (KPD) can facilitate living donor transplantation for candidates with an incompatible donor, but requires waiting for a match while experiencing the morbidity of dialysis. The balance between waiting for KPD vs desensitization or deceased donor transplantation relies on the ability to estimate KPD wait times. We studied donor/candidate pairs in the National Kidney Registry (NKR), a large multicenter KPD clearinghouse, between October 2011 and September 2015 using a competing-risk framework. Among 1894 candidates, 52% were male, median age was 50 years, 66% were white, 59% had blood type O, 42% had panel reactive antibody (PRA)>80, and 50% obtained KPD through NKR. Median times to KPD ranged from 2 months for candidates with ABO-A and PRA 0, to over a year for candidates with ABO-O or PRA 98+. Candidates with PRA 80-97 and 98+ were 23% (95% confidence interval , 6%-37%) and 83% (78%-87%) less likely to be matched than PRA 0 candidates. ABO-O candidates were 67% (61%-73%) less likely to be matched than ABO-A candidates. Candidates with ABO-B or ABO-O donors were 31% (10%-56%) and 118% (82%-162%) more likely to match than those with ABO-A donors. Providers should counsel candidates about realistic, individualized expectations for KPD, especially in the context of their alternative treatment options.

Background:The epidemic of drug overdose deaths in the United States has led to an increase in organ donors. Objective:To characterize donors who died of overdose and to analyze outcomes among transplant recipients. Design:Prospective observational cohort study. Setting:Scientific Registry of Transplant Recipients, 1 January 2000 to 1 September 2017. Participants:138 565 deceased donors; 337 934 transplant recipients at 297 transplant centers. Measurements:The primary exposure was donor mechanism of death (overdose-death donor [ODD], trauma-death donor [TDD], or medical-death donor [MDD]). Patient and graft survival and organ discard (organ recovered but not transplanted) were compared using propensity score-weighted standardized risk differences (sRDs). Results:A total of 7313 ODDs and 19 897 ODD transplants (10 347 kidneys, 5707 livers, 2471 hearts, and 1372 lungs) were identified. Overdose-death donors accounted for 1.1% of donors in 2000 and 13.4% in 2017. They were more likely to be white (85.1%), aged 21 to 40 years (66.3%), infected with hepatitis C virus (HCV) (18.3%), and increased-infectious risk donors (IRDs) (56.4%). Standardized 5-year patient survival was similar for ODD organ recipients compared with TDD organ recipients (sRDs ranged from 3.1% lower to 3.9% higher survival) and MDD organ recipients (sRDs ranged from 2.1% to 5.2% higher survival). Standardized 5-year graft survival was similar between ODD and TDD grafts (minimal difference for kidneys and lungs, marginally lower [sRD, -3.2%] for livers, and marginally higher [sRD, 1.9%] for hearts). Kidney discard was higher for ODDs than TDDs (sRD, 5.2%) or MDDs (sRD, 1.5%); standardization for HCV and IRD status attenuated this difference. Limitation:Inability to distinguish between opioid and nonopioid overdoses. Conclusion:In the United States, transplantation with ODD organs has increased dramatically, with noninferior outcomes in transplant recipients. Concerns about IRD behaviors and hepatitis C among donors lead to excess discard that should be minimized given the current organ shortage. Primary Funding Source:National Institutes of Health.

OBJECTIVE:To evaluate changes in patient and graft survival for pediatric liver transplant recipients since 2002, and to determine if these outcomes vary by graft type (whole liver transplant, split liver transplant [SLT], and living donor liver transplant [LDLT]). STUDY DESIGN:We evaluated patient and graft survival among pediatric liver-only transplant recipients the PELD/MELD system was implemented using the Scientific Registry of Transplant Recipients. RESULTS:). CONCLUSIONS:In recent years, outcomes after the use of technical variant grafts are comparable with whole grafts, and may be superior for LDLT. Greater use of technical variant grafts might provide an opportunity to increase organ supply without compromising post-transplant outcomes.

Currently, there is debate among the liver transplant community regarding the most appropriate mechanism for organ allocation: urgency-based (MELD) versus utility-based (survival benefit). We hypothesize that MELD and survival benefit are closely associated, and therefore, our current MELD-based allocation already reflects utility-based allocation. We used generalized gamma parametric models to quantify survival benefit of LT across MELD categories among 74 196 adult liver-only active candidates between 2006 and 2016 in the United States. We calculated time ratios (TR) of relative life expectancy with transplantation versus without and calculated expected life years gained after LT. LT extended life expectancy (TR > 1) for patients with MELD > 10. The highest MELD was associated with the longest relative life expectancy (TR = _1.05 1.20_1.37 for MELD 11-15, _2.29 2.49_2.70 for MELD 16-20, _5.30 5.72_6.16 for MELD 21-25, _15.12 16.35_17.67 for MELD 26-30; _39.26 43.21_47.55 for MELD 31-34; _120.04 128.25_137.02 for MELD 35-40). As a result, candidates with the highest MELD gained the most life years after LT: 0.2, 1.5, 3.5, 5.8, 6.9, 7.2 years for MELD 11-15, 16-20, 21-25, 26-30, 31-34, 35-40, respectively. Therefore, prioritizing candidates by MELD remains a simple, effective strategy for prioritizing candidates with a higher transplant survival benefit over those with lower survival benefit.

BACKGROUND:The Organ Procurement and Transplantation Network has implemented medical criteria to determine which candidates are most appropriate for simultaneous liver-kidney (SLK) transplantation in comparison to liver-alone transplantation. We investigated prepolicy center-level variation among SLK listing practice, in light of such criteria. METHODS:We identified 4736 SLK-eligible candidates after Share-35 in the United States. We calculated the proportion of candidates at each center who were listed for SLK transplantation within 6 months of eligibility. Multilevel logistic regression and parametric survival model was used to estimate the center-specific probability of SLK listing, adjusting for patient and center-level characteristics. RESULTS:Among 4736 SLK-eligible candidates, 64.8% were listed for SLK within 6 months of eligibility. However, the percentage of SLK listing ranged from 0% to 100% across centers. African American race, male sex, transplant history, diabetes, and hypertension were associated with a higher likelihood of SLK listing. Conversely, older age was associated with a lower likelihood of SLK listing. After adjusting for candidate characteristics, the percentage of SLK listing still ranged from 3.8% to 80.2% across centers; this wide variation persisted even after further adjusting for center-level characteristics. CONCLUSIONS:There was significant prepolicy center-level variation in SLK listing for SLK-eligible candidates. Implementation of standardized SLK listing practices may reduce center-level variation and equalize access for SLK candidates across the United States.

BACKGROUND:Recent changes in deceased donor organ allocation for livers (Share-35) and kidneys (kidney allocation system) have resulted in broader sharing of organs and increased cold ischemia time (CIT). Broader organ sharing however is not the only cause of increased CIT. METHODS:This was a retrospective registry study of CIT in same-hospital liver transplants (SHLT, n = 4347) and same-hospital kidney transplants (SHKT, n = 9707) between 2004 and 2014. RESULTS:In SHLT, median (interquartile range) CIT was 5.0 (3.5-6.5) hours versus 6.6 (5.1-8.4) hours in other-hospital LT. donation after circulatory death donors, donor biopsy, male recipient, recipient obesity, and previous transplant were associated with increased CIT. Model for End-Stage Liver Disease at transplant of 29+ or status 1a was associated with decreased CIT. SHLT CIT varied by Organ Procurement Organization and transplant-center (P < 0.01), with center median CIT ranging from 2.0 to 7.8 hours across 118 centers. In SHKT, CIT was 13.0 (8.5-19.0) hours versus 16.5 (11.3-22.6) hours in other-hospital KT. Overweight donors, donation after cardiac death donors, right-kidney, donor biopsy, recipient obesity, use of mechanical perfusion, additional KT procedures on the same day, and transplant center annual volume were associated with increased CIT. Older donor age, extended criteria donors, and underweight recipients were associated with decreased CIT. SHKT CIT varied by Organ Procurement Organization and transplant-center (P < 0.001), with center median CIT ranging from 3.3 to 29 hours across 206 centers. Transplant centers with longer SHKT also had longer SHLT (P = 0.01). CONCLUSIONS:Same-hospital transplants already have a significant amount of CIT, even without transporting the organ to another hospital.

OBJECTIVE:African Americans and other minorities are known to face barriers to health care influencing their access to organ transplantation but it is not known whether these barriers exist among pediatric liver transplant waitlist candidates. We sought to determine whether outcomes on the waitlist (ie, mortality, deceased donor liver transplantation [DDLT], and living-donor liver transplantation [LDLT]) varied by race/ethnicity. METHODS:National registry data were studied to estimate the race/ethnicity-specific risk of waitlist mortality, DDLT and LDLT in children (<18 years) waitlisted between March 2002 and March 2015. RESULTS:There was no evidence of racial/ethnic disparities in waitlist mortality. Compared to Caucasians, LDLT varied by race/ethnicity, with only 6.7% African Americans and 10.3% Hispanic children receiving LDLT compared with 12.4% Caucasian, 13.3% Asian, and 9.4% mix/other children. In an adjusted Cox proportional hazards model, African Americans were half as likely as Caucasians to use LDLT (hazard ratio [HR]: 0.410.550.73) but had similar use of DDLT (HR: 0.981.061.16). In a model that considered mortality, DDLT, and LDLT as competing risks, African Americans had significantly reduced incidence of LDLT (subhazard ratio [sHR]: 0.410.560.75) compared to Caucasians, but increased use of DDLT (sHR: 1.061.161.26). CONCLUSIONS:Compared to Caucasian children, African-American children are less likely to use LDLT but have higher rates of DDLT and similar survival on the waitlist. Additional research is necessary to understand the clinical and socioeconomic factors contributing to lower utilization of LDLT among African-American children awaiting transplantation.