Faculty Bibliography

BACKGROUND:End-stage kidney disease (ESKD) patients are living longer, often into older age, and commonly pursue kidney transplantation. Successful aging, a multidimensional construct of physical and social wellbeing, has been expanded and adapted for patients with chronic disease. However, perceptions of, barriers to, and experiences with successful aging among adults with ESKD are unclear and likely differ based on whether they have received a kidney transplant. METHODS:Ten focus groups were held with 39 total ESKD patients aged ≥50 years (19 transplant candidates, 20 transplant recipients). Transcriptions were analyzed thematically by 2 independent coders using an inductive, constant comparative approach. RESULTS:The mean age was 64.8 (SD = 7.5); 51% were African American and 64% were males. Six themes were identified: familiarity with successful aging, perceptions of successful aging after ESKD diagnosis, barriers to successful aging, experiences with successful aging among transplant candidates, experiences with successful aging among transplant recipients, and suggested interventions. While all participants sought to achieve successful aging while living with ESKD, experiences with successful aging differed between candidates and recipients. Candidates struggled with the limitations of dialysis; some viewed transplantation as an opportunity to age successfully, while others were resigned to the drawbacks of dialysis. In contrast, transplant recipients were optimistic about their ability to age successfully, believing their transplant facilitated successful aging. Participants believed support groups for adults with ESKD and more thoughtful health care for aging adults would promote successful aging. CONCLUSIONS:Adults with ESKD may benefit from discussions with their clinicians and caregivers about goals, barriers, and strategies regarding successful aging.

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:Recipients of kidneys from living donors who subsequently develop end-stage renal disease (ESRD) also have higher graft failure, suggesting the 2 donor kidneys share risk factors that could inform recipient outcomes. Given that donor ESRD is rare, an earlier and more common postdonation outcome could serve as a surrogate to individualize counseling and management for recipients. Hypertension is a frequent event before donor ESRD; thus, early postdonation hypertension might indicate higher risk of graft failure. METHODS:We studied Scientific Registry of Transplant Recipients data to quantify the association between early postdonation hypertension and recipient graft failure using propensity score-weighted Cox proportional hazards regression. We also examined the association between postdonation systolic blood pressure and graft failure. RESULTS:Of 37 901 recipients, 2.4% had a donor who developed hypertension within 2 years postdonation. Controlling for donor and recipient characteristics, recipients whose donors developed hypertension had no higher risk for graft failure (adjusted hazard ratio [aHR] 1.03, 95% confidence interval [CI] 0.85-1.25, P = 0.72). This was consistent among subgroups of recipients at higher risk for adverse outcomes due to hyperfiltration: African American recipients (aHR 1.10, 95% CI 0.70-1.73, P = 0.68) and those with ESRD caused by hypertension (aHR 1.10, 95% CI 0.65-1.85, P = 0.73) or diabetes (aHR 0.80, 95% CI 0.56-1.13, P = 0.20). However, graft failure was associated with postdonation systolic blood pressure (per 10 mm Hg, aHR 1.05, 95% CI 1.03-1.08, P < 0.001). CONCLUSIONS:Although postdonation systolic blood pressure is associated with graft failure, the reported diagnosis of hypertension as determined by the requirement for blood pressure treatment early postdonation did not portend a higher risk of recipient graft failure in the same way as eventual postdonation ESRD.

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 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: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.

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: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.

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.

With implementation of the Kidney Allocation System, the growth of kidney paired donation programs, and advances in desensitization and immunosuppression, the outlook for "untransplantable" kidney transplantation candidates has never been more promising. The Kidney Allocation System prioritized compatible matches for candidates with calculated panel-reactive antibody levels of 98%, 99%, or 100% and broadened allocation of non-A1 and non-A1-B subgroup kidneys to blood group type B candidates. Concurrently, the growth of kidney paired donation programs and use of incompatible transplantation as part of kidney paired donation to achieve "more compatible" kidney transplantation has improved options for candidates with an incompatible living donor. Finally, advances in desensitization and immunosuppression have strengthened the ability to manage donor-specific antibodies and antibody-mediated rejection. Although no patient should be labeled "untransplantable" due to blood group type or donor-specific antibody, all candidates should be provided with individualized and realistic counseling regarding their anticipated wait times for deceased donor or kidney paired donation matching, with early referral to expert centers when needed. In this Perspective, we consider blood group type ABO incompatibility, HLA antigen incompatibility, antibody-mediated rejection, kidney paired donation, and recent developments in incompatible transplantation in more depth and recommend an approach to the sensitized candidate.