Faculty Bibliography

BACKGROUND:In March 2020, COVID-19 infections began to rise exponentially in the USA, placing substantial burden on the healthcare system. As a result, there was a rapid change in transplant practices and policies, with cessation of most procedures. Our goal was to understand changes to pediatric kidney transplantation (KT) at the national level during the COVID-19 epidemic. METHODS:Using SRTR data, we examined changes in pediatric waitlist registration, waitlist removal or inactivation, and deceased donor and living donor (DDKT/LDKT) events during the start of the disease transmission in the USA compared with the same time the previous year. RESULTS:) in states with high vs. low COVID activity. Transplant recipients during the pandemic were more likely to have received a DDKT, but had similar calculated panel-reactive antibody (cPRA) values, waitlist time, and cause of kidney failure as before the pandemic. CONCLUSIONS:The COVID-19 pandemic initially reduced access to kidney transplantation among pediatric patients in the USA but has not had a sustained effect.

Although the gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR), little is known about GFR trajectories after transplantation, their determinants, and their association with outcomes. To evaluate these parameters we examined kidney transplant recipients receiving care at 15 academic centers. Patients underwent prospective monitoring of estimated GFR (eGFR) measurements, with assessment of clinical, functional, histological and immunological parameters. Additional validation took place in seven randomized controlled trials that included a total of 14,132 patients with 403,497 eGFR measurements. After a median follow-up of 6.5 years, 1,688 patients developed end-stage kidney disease. Using unsupervised latent class mixed models, we identified eight distinct eGFR trajectories. Multinomial regression models identified seven significant determinants of eGFR trajectories including donor age, eGFR, proteinuria, and several significant histological features: graft scarring, graft interstitial inflammation and tubulitis, microcirculation inflammation, and circulating anti-HLA donor specific antibodies. The eGFR trajectories were associated with progression to end stage kidney disease. These trajectories, their determinants and respective associations with end stage kidney disease were similar across cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the seven randomized control trials. Thus, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

BACKGROUND:Fine particulate matter (particulate matter with diameter <2.5 µm [PM2.5]) is associated with CKD progression and may impact the health of patients living with kidney failure. While older (aged ≥65 years) adults are most vulnerable to the impact of PM2.5, it is unclear whether older patients on dialysis are at elevated risk of mortality when exposed to fine particulate matter. METHODS:Older adults initiating dialysis (2010-2016) were identified from US Renal Data System (USRDS). PM2.5 concentrations were obtained from NASA's Socioeconomic Data and Application Center (SEDAC) Global Annual PM2.5 Grids. We investigated the association between PM2.5 and all-cause mortality using Cox proportional hazard models with linear splines [knot at the current Environmental Protection Agency (EPA) National Ambient Air Quality Standard for PM2.5 of 12 μg/m3] and robust variance. RESULTS:For older dialysis patients who resided in areas with high PM2.5, a 10 μg/m3 increase in PM2.5 was associated with 1.16-fold (95% CI: 1.08-1.25) increased risk of mortality; furthermore, those who were female (aHR = 1.26, 95% CI: 1.13-1.42), Black (aHR = 1.31, 95% CI: 1.09-1.59), or had diabetes as a primary cause of kidney failure (aHR = 1.25, 95% CI: 1.13-1.38) were most vulnerable to high PM2.5. While the mortality risk associated with PM2.5 was stronger at higher levels (aHR = 1.19, 95% CI: 1.08-1.32), at lower levels (≤12 μg/m3), PM2.5 was significantly associated with mortality risk (aHR = 1.04, 95% CI: 1.00-1.07) among patients aged ≥75 years (Pslope difference = 0.006). CONCLUSIONS:Older adults initiating dialysis who resided in ZIP codes with PM2.5 levels >12 μg/m3 are at increased risk of mortality. Those aged >75 were at elevated risk even at levels below the EPA Standard for PM2.5.