Faculty Bibliography

BACKGROUND:Observed long-term outcomes no longer reflect the survival trajectory facing pediatric liver transplant (LT) recipients today. We aimed to use national registry data and parametric models to project 20- and 30-year post-transplant outcomes for recently transplanted pediatric LT recipients. METHODS:We conducted a retrospective cohort study of 13,442 first-time pediatric (age <18) LT recipients using 1987 to 2018 Scientific Registry of Transplant Recipients data. We validated the proposed method (ie, to project long-term patient and graft survival using parametric survival models and short-term data) in 2 historic cohorts (1987-1996 and 1997-2006) and estimated long-term projections among patients transplanted between 2007 and 2018. Projections were stratified by raft type, recipient age, and indication for transplant. RESULTS:Parsimonious parametric models with Weibull distribution can be applied to post-transplant data and used to project long-term outcomes for pediatric LT recipients beyond observed data. Projected 20-year patient survival for pediatric LT recipients transplanted in 2007 to 2018 was 84.0% (95% confidence interval 81.5-85.8), compared to observed 20-year survival of 72.8% and 63.6% among those transplanted in 1997 to 2006 and 1987 to 1996, respectively. Projected 30-year survival for pediatric LT recipients in 2007 to 2018 was 80.1% (75.2-82.7), compared to projected 30-year survival of 68.6% (66.1-70.9) in the 1997 to 2006 cohort and observed 30-year survival of 57.5% in the 1987 to 1996 cohort. Twenty- and 30-year patient and graft survival varied slightly by recipient age, graft type, and indication for transplant. CONCLUSIONS:Projected long-term outcomes for recently transplanted pediatric LT recipients are excellent, reflective of substantial improvements in medical care, and informative for physician-patient education and decision making in the current era.

BACKGROUND:Delayed graft function (DGF) is associated with inferior posttransplant outcomes in kidney transplantation. Given these adverse outcomes, we sought to determine the incidence, unique risk factors, and posttransplant outcomes for simultaneous liver kidney (SLK) transplant recipients developing DGF. METHODS:We studied 6214 adult SLK recipients from March 2002 to February 2017 using the Scientific Registry of Transplant Recipients. We determined associations between risk factors and DGF using Poisson multivariate regression and between DGF and graft failure and mortality using Cox proportional hazard analysis. RESULTS:The overall rate of DGF was 21.8%. Risk factors for DGF in the hepatitis C virus (HCV)-negative recipient population included pretransplant dialysis (adjusted incident rate ratio [aIRR] 3.26, P = 0.004), donor body mass index (aIRR 1.25 per 5 kg/m, P = 0.01), and transplantation with a donation after circulatory death (aIRR 5.38, P = 0.001) or imported donor organ (regional share aIRR 1.69, P = 0.03; national share aIRR 4.82, P < 0.001). DGF was associated with a 2.6-fold increase in kidney graft failure (adjusted hazard ratio [aHR] 2.63, P < 0.001), 1.6-fold increase in liver graft failure (aHR 1.62, P < 0.001), and 1.6-fold increase in mortality (aHR 1.62, P < 0.001). CONCLUSIONS:In HCV-negative SLK recipients, recipient pretransplant dialysis and components of kidney graft quality comprise significant risk factors for DGF. Regardless of HCV status, DGF is associated with inferior posttransplant outcomes. Understanding these risk factors during clinical decision-making may improve prevention of DGF and may represent an opportunity to improve posttransplant outcomes.

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first-line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007-2016) to describe use and correlates of AHM use during months 7-12 post-transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta-blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non-DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC-8) guidelines (2014-2016), compared with an earlier period (2007-2013). The median odds ratios generated from case-factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.

BACKGROUND AND OBJECTIVES:In the United States, kidney paired donation networks have facilitated an increasing proportion of kidney transplants annually, but transplant outcome differences beyond 5 years between paired donation and other living donor kidney transplant recipients have not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:), and transplant factors (zero HLA mismatch). RESULTS:=0.2) between National Kidney Registry and control recipients. CONCLUSIONS:Even after transplanting patients with greater risk factors for worse post-transplant outcomes, nationalized paired donation results in equivalent outcomes when compared with control living donor kidney transplant recipients.

BACKGROUND:Given the potential utility of frailty, a clinical phenotype of decreased physiologic reserve and resistance to stressors, to predict postkidney transplant (KT) outcomes, we sought to understand the perceptions and practices regarding frailty measurement in US KT programs. METHODS:Surveys were emailed to American Society of Transplantation Kidney/Pancreas Community of Practice members and 202 US transplant programs (November 2017 to April 2018). Program characteristics were gleaned from Scientific Registry of Transplant Recipients. RESULTS:The 133 responding programs (response rate = 66%) represented 77% of adult KTs and 79% of adult KT candidates in the United States. Respondents considered frailty to be a useful concept in evaluating candidacy (99%) and endorsed a need to develop a frailty measurement specific to KT (92%). Frailty measurement was more common during candidacy evaluation (69%) than during KT admission (28%). Of the 202 programs, 38% performed frailty assessments in all candidates while 23% performed assessments only for older candidates. There was heterogeneity in the frailty assessment method; 18 different tools were utilized to measure frailty. The most common tool was a timed walk test (19%); 67% reported performing >1 tool. Among programs that measure frailty, 53% reported being less likely to list frail patients for KT. CONCLUSIONS:Among US KT programs, frailty is recognized as a clinically relevant construct and is commonly measured at evaluation. However, there is considerable heterogeneity in the tools used to measure frailty. Efforts to identify optimal measurement of frailty using either an existing or a novel tool and subsequent standardization of its measurement and application across KT programs should be considered.

We represent a group of investigators funded by the National Institutes of Health (R01AI120938, U01AI134591, U01AI138897) to conduct a prospective multicenter study of the landscape of HIV-infected (HIV+) donors and two prospective multicenter trials comparing outcomes between HIV+ recipients of HIV+ and non-HIV+ donor kidneys and livers. These clinical trials are ongoing (NCT02602262, NCT03500315, NCT03734393).

BACKGROUND:The short physical performance battery (SPPB) test is an objective measurement of lower extremity function (walk speed, balance, chair stands). SPPB impairment is associated with longer length of stay and increased mortality in kidney transplant (KT) recipients. Furthermore, the SPPB test may represent an objective quantification of the "foot of the bed test" utilized by clinicians; therefore, impairment may translate with decreased access to KT. METHODS:We studied 3255 participants (2009-2018) at 2 KT centers. SPPB impairment was defined as a score of ≤10. We estimated time to listing, waitlist mortality, and transplant rate by SPPB impairment status using Cox proportional hazards, competing risks, and Poisson regression. RESULTS:The mean age was 54 years (SD = 14; range 18-89) and 54% had SPPB impairment. Impaired participants were less likely to be listed for KT (adjusted hazard ratio: 0.70, 95% CI: 0.64-0.77, P < 0.001). Also, once listed, impaired candidates had a 1.6-fold increased risk of waitlist mortality (adjusted subhazard ratio: 1.56, 95% CI: 1.18-2.06, P = 0.002). Furthermore, impaired candidates were transplanted 16% less frequently (adjusted incidence rate ratio: 0.84, 95% CI: 0.73-0.98, P = 0.02). CONCLUSIONS:SPPB impairment was highly prevalent in KT candidates. Impaired candidates had decreased chance of listing, increased risk of waitlist mortality, and decreased rate of KT. Identification of robust KT candidates and improvement in lower extremity function are potential ways to improve survival on the waitlist and access to KT.

BACKGROUND:Evidence about the reliability of pre-implantation biopsy is still conflicting, depending on both biopsy type and pathologist's expertise. Aim of the study is to evaluate the agreement of general v specialist pathologists and to compare scores on biopsy and whole organs in a set of discarded kidneys. METHODS:46 discarded kidneys were identified with their corresponding biopsies. The biopsies were reviewed by three general and two specialist pathologists, blinded to the original report, according to Remuzzi score. The intraclass correlation coefficient (ICC) was calculated for both groups. Discarded kidneys were scored according to Remuzzi score by a single specialist pathologist. Biopsies and organs were compared by Wilcoxon signed rank test. Weighted κ coefficients between biopsy and organ scores were also calculated. RESULTS:Specialist pathologists achieved higher values of ICC, reaching excellent or good agreement in most of the parameters, while general pathologists values were mainly fair or good. On whole organs, scores were consistently lower than biopsies, with a significant difference in most of the parameters. Weighted κ coefficient was slight or fair for most of the parameters. CONCLUSIONS:Our data suggests that the creation of a pool of specialist pathologists would improve organ utilization. Moreover, biopsies are not representative of the whole organ. As the Remuzzi score on biopsy is a major reasons for discard, a quota of transplantable kidneys may be erroneously discarded. Refinement in Remuzzi cut-offs based on expert reporting and recognition of sampling error of biopsies in correlation with clinical outcome data should be undertaken.

BACKGROUND:Early steroid withdrawal (ESW) is associated with acceptable outcomes in kidney transplant (KT) recipients. Recipients with delayed graft function (DGF), however, often have a suboptimal allograft milieu, which may alter the risk/benefit equation for ESW. This may contribute to varying practices across transplant centers. METHODS:Using the Scientific Registry of Transplant Recipients, we studied 110,019 adult deceased-donor KT recipients between 2005 and 2017. We characterized the association of DGF with the use of ESW versus continued steroid maintenance across KT centers, and quantified the association of ESW with acute rejection, graft failure, and mortality using multivariable logistic and Cox regression with DGF-ESW interaction terms. RESULTS:=0.6). CONCLUSIONS:KT centers in the United States use ESW inconsistently in recipients with DGF. Our findings suggest ESW may lead to worse KT outcomes in recipients with DGF.

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation ("oldest kidneys") and prolonged cold ischemia time ("coldest kidneys") on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death-censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.