Faculty Bibliography

BACKGROUND:Sarcopenia and myosteatosis are indicators of abnormal body composition (BC). Computed tomography (CT) imaging has proven to be an accurate modality for BC quantification in kidney transplantation (KT). We tested whether pre-KT CT-based BC was associated with both all-cause graft loss (ACGL) and mortality among adult recipients from two centers (Johns Hopkins Hospital [JHH] and University Medical Center Groningen [UMCG]). METHODS:Patients who underwent a KT between 2003 and 2020 were followed for a median (interquartile range) follow-up of 6.4 (4.6-8.5) years at JHH and 6.3 (5.1-7.5) years at UMCG. Cox proportional hazard models were used to estimate the associations of BC with ACGL/ mortality. Fine and Gray regression analysis was performed to assess the association between BC and death-censored graft loss. Prior to KT, 49% of recipients had sarcopenia and 66% had myosteatosis. RESULTS:In total 608 patients were included from JHH (N= 294) and UMCG (N=314). Sarcopenia was not associated with post-KT outcomes. Myosteatosis was associated with a higher risk of ACGL (adjusted hazard ratio 1.78, 95%CI:1.08 - 2.93) and mortality (adjusted hazard ratio 2.35, 95%CI: 1.27 - 4.33) at JHH, but showed no significant association at UMCG after adjusting for confounders. Myosteatosis did not show a significant association with death-censored graft loss at both centers. CONCLUSION/CONCLUSIONS:Myosteatosis ascertained from existing CT scans could help identify recipients at higher risk for ACGL who may benefit most from prehabilitation.

BACKGROUND:To encourage high-quality, reduced-cost care for total joint arthroplasty (TJA), the Centers of Medicare & Medicaid Services mandated a pay-for-performance model, the Comprehensive Care for Joint Replacement (CJR), as part of the Patient Protection and Affordable Care Act (PPACA). The CJR incentivizes cost containment, and it was anticipated that its implementation would reduce access to TJA for high-cost populations. Patients with end-stage kidney disease (ESKD) undergoing kidney replacement therapy (dialysis and kidney transplant) are costly compared with healthier patients, but it was unknown whether this population lost access to hip and knee replacement because of CJR implementation. This population allows study of whether TJA is accessible for medically complex patients whose risk of surgical complications has been mitigated, as kidney transplantation improves outcomes compared with dialysis, allowing evaluation as to whether access improved when patients crossed over from dialysis to transplantation. Because all patients with ESKD are included in a mandated national registry, we can quantify whether access changed for patients who underwent dialysis and transplantation. QUESTIONS/PURPOSES/OBJECTIVE:(1) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD receiving dialysis? (2) How did the rate of TJA change amid the shift to bundled payments for patients with ESKD after kidney transplant? METHODS:This was an observational cohort study from 2008 to 2018 using the United States Renal Data System, a mandatory national registry that allows for the opportunity to study all individuals with ESKD. During the study period, we identified 1,324,614 adults undergoing routine dialysis and 187,212 adult kidney transplant recipients; after exclusion for non-Medicare primary insurance (n = 785,224 for dialysis and 78,011 for transplant), patients who were 100 years or older (n = 79 and 0, respectively), those who resided outside of 50 US states and Puerto Rico (n = 781 and 87, respectively), missing dialysis status for the dialysis cohort (n = 8658), and multiorgan transplant recipients for the transplant cohort (n = 2442), our study population was 40% (529,872) of patients who underwent routine dialysis and 57% (106,672) of adult kidney transplant recipients, respectively. TJA was ascertained using Medicare Severity Diagnosis Related Groups and ICD-9 and ICD-10 codes. We divided the study period by PPACA (January 1, 2014, to March 31, 2016) and CJR (April 1, 2016, to December 31, 2018) implementation and compared the incidence of TJA by era using mixed-effects Poisson regression adjusting for calendar time and clinical and demographic variables. RESULTS:After adjustment for linear temporal trend and patient case mix, there was no evidence of association between policy implementation and the incidence of TJA. In the dialysis cohort, the adjusted incidence rate ratio (IRR) for TJA was 1.06 (95% confidence interval [CI] 0.98 to 1.14; p = 0.2) comparing PPACA with the previous period and 1.02 (95% CI 0.96 to 1.08; p = 0.6) comparing CJR with the previous periods. Similarly, in the transplant cohort, the adjusted IRR for TJA was 0.82 (95% CI 0.67 to 1.02; p = 0.07) comparing PPACA with the previous period and 1.10 (95% CI 0.94 to 1.28; p = 0.9) comparing CJR with the previous periods. CONCLUSION/CONCLUSIONS:There was no loss in access to TJA for medically complex patients receiving kidney replacement therapy. The increase in TJA incidence for patients after kidney transplant and decrease for patients receiving dialysis suggest that surgeons continued to provide care for higher risk patients whose risk of morbidity or mortality with total joint replacement has been maximally improved after transplantation. LEVEL OF EVIDENCE/METHODS:Level III, prognostic study.

Community input enhances the impact of research. Yet, there are challenges when eliciting community perspectives in nephrology/transplant research: recruitment of patients across a wide spectrum of familiarity with kidney disease; a lack of trust from marginalized patients because of health care barriers, institutionalized structural racism, and historical harm; and retention of members facing high burden of care. To address these challenges, we drafted a mission and formed a community advisory board to provide input on nephrology/transplant research. We worked with kidney disease community organizations that prioritize diversity and equity to recruit members with chronic kidney disease, end-stage kidney disease, or a kidney transplant, as well as nephrology/transplant caregivers and kidney donors. We formed a diverse group of 9 members and received feedback on 5 research proposals over 4 quarterly meetings, bridging a communication gap between community perspectives and researchers. The collaborative environment stimulated feedback that improved our nephrology/transplant research to reflect the perspectives of those most affected by research findings. Eight members have remained active for more than 1 year. In this collaborative paper, we describe our process of forming a nephrology/transplant community advisory board, and participants highlight the benefits of sharing their lived experiences to improve and amplify the impact of nephrology/transplant research.

BACKGROUND:Glucagon-like peptide-1 receptor agonists (GLP1RA) provide survival benefits in people with diabetes, including kidney transplant (KT) recipients with pre-existing diabetes. Post-transplant diabetes mellitus (PTDM) is common, but the benefits of GLP1RAs remain undefined in this population. We aim to describe current usage practices and outcomes in PTDM. METHODS:We used USRDS and Medicare claims data (2013-2022) to conduct a drug utilization profile of GLP1RA among 7681 first-time adult KT recipients with PTDM. We used survival analysis to estimate GLP1RA initiation incidence and associated patient, graft, and safety outcomes. RESULTS:A total of 430 adult KT recipients with PTDM were prescribed GLP1RA. Dulaglutide was the most commonly prescribed medication (46.1%). The 5-year cumulative incidence of GLP-1 receptor agonists prescription was 9.8%. Median (interquartile range) time from PTDM diagnosis to first prescription was 1.7 (0.6, 3.4) years. GLP1RA use was not associated with a difference in the risk of mortality or graft failure but was associated with a 1.80-fold (95% confidence interval [CI]: 1.11-2.91) increased risk of diabetic retinopathy. No increased risk of pancreatitis, biliary complications, or medullary thyroid cancer were identified. CONCLUSIONS:GLP1RA use in KT recipients with PTDM was not associated with graft or patient survival, though longer follow-up is necessary. GLP1RA use was associated with an increased risk of diabetic retinopathy, and care should be taken when initiating these agents.

BACKGROUND/UNASSIGNED:) and long-term premature cognitive aging. We tested whether CMV was associated with post-KT cognitive impairment. METHODS/UNASSIGNED:In a 2-center prospective cohort study of 574 KTRs (mean age: 54.7 y), we obtained CMV donor/recipient (D/R) serostatus and measured pre- and post-KT cognitive function using the Modified Mini-Mental State Examination. We estimated post-KT global cognitive function trajectories by CMV serostatus using adjusted mixed effect models with linear spline terms. RESULTS/UNASSIGNED:(slope = 0.01 points/year; 95% CI, -1.87 to 1.89). CONCLUSIONS/UNASSIGNED:KTRs may be at elevated risk for post-KT cognitive impairment; clinicians may prioritize early interventions in this population.

IMPORTANCE/UNASSIGNED:Total particulate matter with a diameter of 2.5 µm or less (PM2.5) has been found to be associated with adverse posttransplant outcomes among kidney transplant (KT) recipients. However, PM2.5 is a complex mixture of multiple constituents, all of which have different toxicity profiles, so it is not clear which constituents are most associated with adverse outcomes among KT recipients. OBJECTIVE/UNASSIGNED:To investigate the associations between PM2.5 constituents and post-KT outcomes among KT recipients. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:This cohort study was conducted among patients who received a KT between January 2000 and December 2016 and lived in the contiguous United States. Follow-up continued through December 2021, and data were analyzed from August 2023 to May 2025. EXPOSURES/UNASSIGNED:Fifteen PM2.5 constituents (including elemental carbon, ammonium, nitrate, organic carbon [OC], sulfate [SO42-], bromine, calcium, copper, iron, potassium, nickel [Ni], lead [Pb], silicon, vanadium, and zinc) at the zip code of residence prior to KT, estimated from ensembled machine learning models. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Adverse post-KT outcomes included acute rejection, delayed graft function (DGF), death-censored graft failure (DCGF), and mortality. The association of PM2.5 constituents and the outcome were evaluated with weighted quantile sum regressions. RESULTS/UNASSIGNED:In total, 192 587 KT recipients were included in the analysis (mean [SD] age at transplant, 51.56 [13.47] years; 75 021 [39.0%] female; 51 455 [26.7%] Black, 28 586 [14.8%] Hispanic, and 97 927 [50.8%] White). Each decile increase in the PM2.5 constituent mixture was associated with a 6.8% (95% CI, 5.8%-7.8%) and 3.6% (95% CI, 2.1%-5.1%) increase in the odds of DGF and acute rejection, respectively. OC and Ni contributed the largest weights to the observed association between PM2.5 mixture and DGF (OC: relative importance, 35.6%; Ni: relative importance, 34.4%), while Pb had the largest impact on acute rejection (relative importance, 75.0%). Each decile increase in PM2.5 constituent mixture was associated with a 4.7% (95% CI, 3.3%-6.3%) and 3.9% (95% CI, 2.5%-5.2%) increase in the hazard of DCGF and all-cause mortality, respectively. The constituent that contributed the largest weight to the observed association between PM2.5 mixture and long-term post-KT outcomes was SO42- (relative importance, 51.3%). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this cohort study, PM2.5 constituents were associated with an increased risk of adverse posttransplant outcomes among KT recipients. Of the PM2.5 constituents included in this study, SO42- contributed most to long-term outcomes, while Pb, OC, and Ni were more associated with short-term outcomes.

INTRODUCTION/BACKGROUND:Early post-kidney transplant (KT) changes likely impact body composition, resulting in adverse post-KT outcomes. We estimated post-KT trajectories of computed tomography (CT)-based muscle quantity/quality and tested whether they were associated with mortality and death-censored graft loss (DCGL) among frail and nonfrail recipients. METHODS:We leveraged a cohort of 294 adult KT recipients (December 2008-February 2020) with CT measurements (muscle quantity: skeletal muscle index; muscle quality: skeletal muscle radiation attenuation). We used mixed linear regression models to estimate 3-year post-KT muscle quantity/quality trajectories. Cox proportional hazard models quantified the association between time-varying pre-/post-KT muscle mass measurements and post-KT mortality and DCGL. RESULTS:) was associated with elevated mortality risk (aHR: 2.00, 95% CI: 1.08-3.70), but not among nonfrail recipients. Among older (≥65 years) recipients, lower muscle quantity was associated with increased DCGL risk (aHR: 2.70, 95% CI: 1.04-7.04), but not among younger recipients. Lower muscle quality (per 10 HU) was associated with elevated mortality (aHR: 2.23, 95% CI: 1.61-3.08) and DCGL (aHR: 1.90, 95% CI: 1.16-3.12) risk. CONCLUSION/CONCLUSIONS:Lower pre-/post-KT muscle quantity/quality were associated with higher risks of post-KT adverse outcomes. Pre-/post-KT rehabilitation to improve muscle quantity/quality may be an effective clinical intervention to minimize risks of adverse post-KT outcomes.