Faculty Bibliography

BACKGROUND:Kidneys from infectious risk donors (IRD) confer substantial survival benefit in adults, yet the benefit of IRD kidneys to pediatric candidates remains unclear in the context of high waitlist prioritization. METHODS:Using 2010-2016 Scientific Registry of Transplant Recipients data, we studied 2417 pediatric candidates (age <18 y) who were offered an IRD kidney that was eventually used for transplantation. We followed candidates from the date of first IRD kidney offer until the date of death or censorship and used Cox regression to estimate mortality risk associated with IRD kidney acceptance versus decline, adjusting for age, sex, race, diagnosis, and dialysis time. RESULTS:Over the study period, 2250 (93.1%) pediatric candidates declined and 286 (11.8%) accepted an IRD kidney offer; 119 (41.6%) of the 286 had previously declined a different IRD kidney. Cumulative survival among those who accepted versus declined the IRD kidney was 99.6% versus 99.4% and 96.3% versus 97.8% 1 and 6 years post decision, respectively (P = 0.1). Unlike the substantial survival benefit seen in adults (hazard ratio = 0.52), among pediatric candidates, we did not detect a survival benefit associated with accepting an IRD kidney (adjusted hazard ratio: 0.791.723.73, P = 0.2). However, those who declined IRD kidneys waited a median 9.6 months for a non-IRD kidney transplant (11.2 mo among those <6 y, 8.8 mo among those on dialysis). Kidney donor profile index (KDPI) of the eventually accepted non-IRD kidneys (median = 13, interquartile range = 6-23) was similar to KDPI of the declined IRD kidneys (median = 16, interquartile range = 9-28). CONCLUSIONS:Unlike in adults, IRD kidneys conferred no survival benefit to pediatric candidates, although they did reduce waiting times. The decision to accept IRD kidneys should balance the advantage of faster transplantation against the risk of infectious transmission.

The Kidney Allocation System (KAS) has resulted in fewer pediatric kidneys being allocated to pediatric deceased donor kidney transplant (pDDKT) recipients. This had prompted concerns that post-pDDKT outcomes may worsen. To study this, we used SRTR data to compare the outcomes of 953 pre-KAS pDDKT (age <18 years) recipients (December 4, 2012-December 3, 2014) with the outcomes of 934 post-KAS pDDKT recipients (December 4, 2014-December 3, 2016). We analyzed mortality and graft loss by using Cox regression, delayed graft function (DGF) by using logistic regression, and length of stay (LOS) by using negative binomial regression. Post-KAS recipients had longer pretransplant dialysis times (median 1.26 vs 1.07 years, P = .02) and were more often cPRA 100% (2.0% vs 0.1%, P = .001). Post-KAS recipients had less graft loss than pre-KAS recipients (hazard ratio [HR]: _0.35 0.54_0.83 , P = .005) but no statistically significant differences in mortality (HR: _0.29 0.72_1.83 , P = .5), DGF (odds ratio: _0.93 1.32_1.93 , P = .2), and LOS (LOS ratio: _0.96 1.06_1.19 , P = .4). After adjusting for donor-recipient characteristics, there were no statistically significant post-KAS differences in mortality (adjusted HR: _0.37 1.04_2.92 , P = .9), DGF (adjusted odds ratio: _0.94 1.41_2.13 , P = .1), or LOS (adjusted LOS ratio: _0.93 1.04_1.16 , P = .5). However, post-KAS pDDKT recipients still had less graft loss (adjusted HR: _0.38 0.59_0.91 , P = .02). KAS has had a mixed effect on short-term posttransplant outcomes for pDDKT recipients, although our results are limited by only 2 years of posttransplant follow-up.

Information about wait-list time has been reported as one of the single most frequently asked questions by individuals awaiting a transplant but data regarding wait-list time have not been processed in a useful way for pediatric candidates. To predict chance of receiving a DDLT, we identified 6471 pediatric (<18 years), non status-1A, liver-only transplant candidates between 2006 and 2017 from the SRTR. Cox regression with shared frailty for DSA level effect was used to model the association of blood type, weight, allocation PELD and MELD, and DSA with chance of DDLT. Jackknife technique was used for validation. Median (interquartile range) wait-list time was 100 (34-309) days. Non-O Blood type, higher PELD/MELD score at listing, and DSA were associated with increased chance of DDLT, while age 1-5 years and 10-18 years was associated with lower chance of DDLT (P < 0.001 for all variables). Our model accurately predicted chance of transplant (C-statistic = 0.68) and was able to predict DDLT at specific follow-up times (eg, 3 months). This model can serve as the basis for an online tool that would provide useful information for pediatric wait-list candidates.

BACKGROUND AND OBJECTIVES:The risk of hypertension attributable to living kidney donation remains unknown as does the effect of developing postdonation hypertension on subsequent eGFR. We sought to understand the association between living kidney donation, hypertension, and long-term eGFR by comparing donors with a cohort of healthy nondonors. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We compared 1295 living kidney donors with median 6 years of follow-up with a weighted cohort of 8233 healthy nondonors. We quantified the risk of self-reported hypertension using a parametric survival model. We examined the association of hypertension with yearly change in eGFR using multilevel linear regression and clustering by participant, with an interaction term for race. RESULTS:=0.01, respectively, after hypertension). CONCLUSIONS:Kidney donors are at higher risk of hypertension than similar healthy nondonors, regardless of race. Donors who developed hypertension had a plateau in the usual postdonation increase of eGFR.

BACKGROUND:The Organ Procurement and Transplantation Network implemented Share 35 on June 18, 2013, to broaden deceased donor liver sharing within regional boundaries. We investigated whether increased sharing under Share 35 impacted geographic disparity in deceased donor liver transplantation (DDLT) across donation service areas (DSAs). METHODS:Using Scientific Registry of Transplant Recipients June 2009 to June 2017, we identified 86 083 adult liver transplant candidates and retrospectively estimated Model for End-Stage Liver Disease (MELD)-adjusted DDLT rates using nested multilevel Poisson regression with random intercepts for DSA and transplant program. From the variance in DDLT rates across 49 DSAs and 102 programs, we derived the DSA-level median incidence rate ratio (MIRR) of DDLT rates. MIRR is a robust metric of heterogeneity across each hierarchical level; larger MIRR indicates greater disparity. RESULTS:MIRR was 2.18 pre-Share 35 and 2.16 post-Share 35. Thus, 2 candidates with the same MELD in 2 different DSAs were expected to have a 2.2-fold difference in DDLT rate driven by geography alone. After accounting for program-level heterogeneity, MIRR was attenuated to 2.10 pre-Share 35 and 1.96 post-Share 35. For candidates with MELD 15-34, MIRR decreased from 2.51 pre- to 2.27 post-Share 35, and for candidates with MELD 35-40, MIRR increased from 1.46 pre- to 1.51 post-Share 35, independent of program-level heterogeneity in DDLT. DSA-level heterogeneity in DDLT rates was greater than program-level heterogeneity pre- and post-Share 35. CONCLUSIONS:Geographic disparity substantially impacted DDLT rates before and after Share 35, independent of program-level heterogeneity and particularly for candidates with MELD 35-40. Despite broader sharing, geography remains a major determinant of access to DDLT.

Pediatric kidney transplant candidates often have multiple potential living donors (LDs); no evidence-based tool exists to compare potential LDs, or to decide between marginal LDs and deceased donor (DD) kidney transplantation (KT). We developed a pediatric living kidney donor profile index (P-LKDPI) on the same scale as the DD KDPI by using Cox regression to model the risk of all-cause graft loss as a function of living donor characteristics and DD KDPI. HLA-B mismatch (adjusted hazard ratio [aHR] per mismatch = _1.04 1.27_1.55 ), HLA-DR mismatch (aHR per mismatch = _1.02 1.23_1.49 ), ABO incompatibility (aHR = _1.20 3.26_8.81 ), donor systolic blood pressure (aHR per 10 mm Hg = _1.01 1.07_1.18 ), and donor estimated GFR (eGFR; aHR per 10 mL/min/1.73 m² = _0.88 0.94_0.99 ) were associated with graft loss after LDKT. Median (interquartile range [IQR]) P-LKDPI was -25 (-56 to 12). 68% of donors had P-LKDPI <0 (less risk than any DD kidney) and 25% of donors had P-LKDPI >14 (more risk than median DD kidney among pediatric KT recipients during the study period). Strata of LDKT recipients of kidneys with higher P-LKDPI had a higher cumulative incidence of graft loss (39% at 10 years for P-LDKPI ≥20, 28% for 20> P-LKDPI ≥-20, 23% for -20 > P-LKDPI ≥-60, 19% for P-LKDPI <-60 [log rank P < .001]). The P-LKDPI can aid in organ selection for pediatric KT recipients by allowing comparison of potential LD and DD kidneys.

BACKGROUND:Despite providing survival benefit, increased risk for infectious disease (IRD) kidney offers are declined at 1.5 times the rate of non-IRD kidneys. Elucidating sources of variation in IRD kidney offer acceptance may highlight opportunities to expand use of these life-saving organs. METHODS:To explore center-level variation in offer acceptance, we studied 6765 transplanted IRD kidneys offered to 187 transplant centers between 2009 and 2017 using Scientific Registry of Transplant Recipients data. We used multilevel logistic regression to determine characteristics associated with offer acceptance and to calculate the median odds ratio (MOR) of acceptance (higher MOR indicates greater heterogeneity). RESULTS:Higher quality kidneys (per 10 units kidney donor profile index; adjusted odds ratio [aOR], 0.94; 95% confidence interval [CI], 0.92-0.95), higher yearly volume (per 10 deceased donor kidney transplants; aOR, 1.08, 95% CI, 1.06-1.10), smaller waitlist size (per 100 candidates; aOR, 0.97; 95% CI, 0.95-0.98), and fewer transplant centers in the donor service area (per center; aOR, 0.88; 95% CI, 0.85-0.91) were associated with greater odds of IRD acceptance. Adjusting for donor and center characteristics, we found wide heterogeneity in IRD offer acceptance (MOR, 1.96). In other words, if listed at a center with more aggressive acceptance practices, a candidate could be 2 times more likely to have an IRD kidney offer accepted. CONCLUSIONS:Wide national variation in IRD kidney offer acceptance limits access to life-saving kidneys for many transplant candidates.

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007-2016) to examine associations (adjusted hazard ratio, _LCL aHR_UCL ) of post-donation fills of antidiabetic medications (ADM, insulin or non-insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, _3.36 4.59_6.27 ). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9-year incidence, 6.87% vs 1.85%, aHR, _3.55 5.00_7.04 ). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1-year post-donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m² by year 1 was associated with increased risk of subsequent ADM use (aHR, _1.03 1.48_2.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.

The number of live kidney donors has declined since 2005. This decline parallels the evolving knowledge of risk for biologically related, black, and younger donors. To responsibly promote donation, we sought to identify declining low-risk donor subgroups that might serve as targets for future interventions. We analyzed a national registry of 77 427 donors and quantified the change in number of donors per 5-year increment from 2005 to 2017 using Poisson regression stratified by donor-recipient relationship and race/ethnicity. Among related donors aged <35, 35 to 49, and ≥50 years, white donors declined by 21%, 29%, and 3%; black donors declined by 30%, 31%, and 12%; Hispanic donors aged <35 and 35 to 49 years declined by 18% and 15%, and those aged ≥50 increased by 10%. Conversely, among unrelated donors aged <35, 35 to 49, and ≥50 years, white donors increased by 12%, 4%, and 24%; black donors aged <35 and 35 to 49 years did not change but those aged ≥50 years increased by 34%; Hispanic donors increased by 16%, 21%, and 46%. Unlike unrelated donors, related donors were less likely to donate in recent years across race/ethnicity. Although this decline might be understandable for related younger donors, it is less understandable for lower-risk related older donors (≥50 years). Biologically related older individuals are potential targets for interventions to promote donation.

Children receiving a LDLT have superior post-transplant outcomes, but this procedure is only used for 10% of transplant recipients. Better understanding about barriers toward LDLT and the sociodemographic characteristics that influence these underlying mechanisms would help to inform strategies to increase its use. We conducted an online, anonymous survey of parents/caregivers for children awaiting, or have received, a liver transplant regarding their knowledge and attitudes about LDLT. The survey was completed by 217 respondents. While 97% of respondents understood an individual could donate a portion of their liver, only 72% knew the steps in evaluation, and 69% understood the donor surgery was covered by the recipient's insurance. Individuals with public insurance were less likely than those with private insurance to know the steps for LDLT evaluation (44% vs 82%; P < 0.001). Respondents with public insurance were less likely to know someone that had been a living donor (44% vs 56%; P = 0.005) as were individuals without a college degree (64% vs 85%; P = 0.007). Nearly all respondents generally trusted their healthcare team. Among respondents, 82% believed they were well-informed about LDLT but individuals with public insurance were significantly less likely to feel well-informed (67% vs 87%; P = 0.03) and to understand how donor surgery might impact donor work/time off (44% vs 81%; P = 0.001). Substantial gaps exist in parental understanding about LDLT, including its evaluation, potential benefits, and complications. Greater emphasis on addressing these barriers, especially to individuals with fewer resources, will be helpful to expand the use of LDLT.