Faculty Bibliography

Kidney transplantation (KT) experts did not support the use of subjective unintentional weight loss to measure shrinking in the physical frailty phenotype (PFP); a clinically feasible and predictive measure of shrinking is needed. To test whether unintentional weight loss could be replaced by an assessment of sarcopenia using existing CT scans, we performed a prospective cohort study of adult KT recipients with original PFP (oPFP) measured at admission (December 2008-February 2020). We ascertained sarcopenia by calculating skeletal muscle index from available, clinically obtained CTs within 1-year pre-KT (male < 50 cm² /m² ; female < 39 cm² /m² ) and combined it with the original four components to determine new PFP (nPFP) scores. Frailty was classified by frailty score: 0: non-frail; 1-2: pre-frail; ≥3: frail. Mortality and graft loss hazard ratios (HRs) were estimated using adjusted Cox proportional hazard models. Model discrimination was quantified using Harrell's C-statistic. Among 1113 recipients, 18.6% and 17.1% were frail by oPFP and nPFP, respectively. Compared to non-frail recipients, frail patients by either PFP had higher risks of mortality (oPFP HR = 1.67, 95% CI: 1.07-2.62, C = 0.710; nPFP HR = 1.68, 95% CI: 1.06-2.66, C = 0.710) and graft loss (oPFP HR = 1.67, 95% CI: 1.17-2.40, C = 0.631; nPFP HR = 1.66, 95% CI: 1.15-2.40, C = 0.634) with similar discriminations. oPFP and nPFP are equally useful in risk prediction for KT recipients; oPFP may aid in screening patients for pre-KT interventions, while nPFP may assist in nuanced clinical decision-making.

Background/UNASSIGNED:Few reports have focused on newer coronavirus disease 2019 (COVID-19) therapies (remdesivir, dexamethasone, and convalescent plasma) in solid organ transplant recipients; concerns had been raised regarding possible adverse impact on allograft function or secondary infections. Methods/UNASSIGNED:We studied 77 solid organ transplant inpatients with COVID-19 during 2 therapeutic eras (Era 1: March-May 2020, 21 patients; and Era 2: June-November 2020, 56 patients) and 52 solid organ transplant outpatients. Results/UNASSIGNED:In Era 1, no patients received remdesivir or dexamethasone, and 4 of 21 (19.4%) received convalescent plasma, whereas in Era 2, remdesivir (24/56, 42.9%), dexamethasone (24/56, 42.9%), and convalescent plasma (40/56, 71.4%) were commonly used. Mortality was low across both eras, 4 of 77 (5.6%), and rejection occurred in only 2 of 77 (2.8%) inpatients; infections were similar in hypoxemic patients with or without dexamethasone. Preexisting graft dysfunction was associated with greater need for hospitalization, higher severity score, and lower survival. Acute kidney injury was present in 37.3% of inpatients; renal function improved more rapidly in patients who received remdesivir and convalescent plasma. Post-COVID-19 renal and liver function were comparable between eras, out to 90 d. Conclusions/UNASSIGNED:Newer COVID-19 therapies did not appear to have a deleterious effect on allograft function, and infectious complications were comparable.

BACKGROUND:In older adults (≥65) access to and outcomes following kidney transplantation (KT) have improved over the past three decades. It is unknown if there were parallel trends in re-KT. We characterized the trends, changing landscape, and outcomes of re-KT in older adults. METHODS:Among the 44,149 older kidney-only recipients (1995-2016) in the Scientific Registry of Transplant Recipients, we identified 1,743 who underwent re-KT. We analyzed trends and outcomes (mortality, death-censored graft failure [DCGF]) by eras (1995-2002, 2003-2014 and 2015-2016) that were defined by changes to the ECD and KDPI policies. RESULTS:Among all older kidney-only recipients during 1995-2002, 2003-2014, 2015-2016 the proportion that were re-KTs increased from 2.7%-4.2%-5.7% p<0.001, respectively. Median age at re-KT (67-68-68, p=0.04), years on dialysis after graft failure (1.4-1.5-2.2, p=0.003), donor age (40.0-43.0-43.5, p=0.04), proportion with PRA 80-100 (22.0%-32.7%-48.7%, p<0.001) and donations after circulatory death (1.1%-13.4%-19.5%, p<0.001) have increased. Despite this, the 3-year cumulative incidence for mortality (22.3%-19.1%-11.5%, p=0.002) and DCGF (13.3%-10.0%-5.1%, p=0.01) decreased over time. Compared with deceased donor re-transplant recipients during 1995-2002, those during 2003-2014 and 2015-2016 had lower mortality hazard (aHR=0.78, 95%CI:0.63-0.86 and aHR=0.55, 95%CI:0.35-0.86, respectively). These declines were noted but not significant for DCGF and in living donor re-KTs. CONCLUSIONS:In older re-transplant recipients, outcomes have improved significantly over time despite higher risk profiles; yet they represent a fraction of the KTs performed. Our results support increasing access to re-KT in older adults; however, approaches to guide the selection and management in those with graft failure need to be explored.

BACKGROUND:Air pollution is associated with cardiopulmonary disease and death in the general population. Fine particulate matter (PM2.5) is particularly harmful due to its ability to penetrate into areas of gas exchange within the lungs. Persons with advanced lung disease are believed to be particularly susceptible to PM2.5 exposure but few studies have examined the effect of exposure on this population. Here we investigate the association between PM2.5 exposure and adverse waitlist events among lung transplant (LT) candidates. METHODS:US registry data were used to identify LT candidates listed between 1/1/2010-12/31/2016. Annual PM2.5 concentration at year of listing was estimated for each candidate's ZIP Code using NASA's SEDAC Global Annual PM2.5 Grids. We estimated crude and adjusted hazard ratios for adverse waitlist events, defined as death or removal, using Cox proportional hazards regression. RESULTS:Of the 15,075 included candidates, median age at listing was 60, 43.8% were female and 81.7% were non-Hispanic white. Median ZIP Code PM2.5 concentration was 9.06µg/m3. When compared to those living in ZIP Codes with lower PM2.5 exposure (PM2.5 <10.53µg/m3), candidates in ZIP Codes in the highest quartile of PM2.5 exposure (≥10.53µg/m3) had 1.14-fold (95%CI 1.04-1.25) risk of adverse waitlist events. The result remained significant after adjusting for demographics, education, insurance, smoking, lung allocation score, BMI, and blood type (HR=1.17; 95%CI 1.07-1.29). CONCLUSIONS:Elevated ambient PM2.5 concentration was associated with adverse waitlist events among LT candidates. These findings highlight the impact of air pollution on clinical outcomes in this critically ill population.

BACKGROUND:Early steroid withdrawal (ESW) is a viable maintenance immunosuppression strategy in low-risk kidney transplant recipients. A low panel reactive antibody (PRA) may indicate low-risk condition amenable to ESW. We aimed to identify the threshold value of PRA above which ESW may pose additional risk, and to compare the association of ESW with transplant outcomes across PRA strata. METHODS:We studied 121,699 deceased-donor kidney-only recipients in 2002-2017 from SRTR. Using natural splines and ESW-PRA interaction terms, we explored how the associations of ESW with transplant outcomes change with increasing PRA values, and identified a threshold value for PRA. Then, we assessed whether PRA exceeding the threshold modified the associations of ESW with 1-year acute rejection, death-censored graft failure, and death. RESULTS:The association of ESW with acute rejection exacerbated rapidly when PRA exceeded 60. Among PRA≤60 recipients, ESW was associated with a minor increase in rejection (aOR=1.001.051.10) and with a tendency of decreased graft failure (aHR=0.910.971.03). However, among PRA>60 recipients, ESW was associated with a substantial increase in rejection (aOR=1.191.271.36; interaction p<0.001) and with a tendency of increased graft failure (aHR=0.981.081.20; interaction p=0.028). The association of ESW with death was similar between PRA strata (PRA≤60, aHR=0.910.961.01; and PRA>60, aHR=0.900.991.09; interaction p=0.5). CONCLUSIONS:Our findings show that the association of ESW with transplant outcomes is less favorable in recipients with higher PRA, especially those with PRA>60, suggesting a possible role of PRA in the risk assessment for ESW.

BACKGROUND:Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) occurs in critically ill patients with COVID-19. Risks and outcomes remain poorly understood. METHODS:A retrospective cohort study of mechanically ventilated adult patients with COVID-19 admitted to 5 Johns Hopkins hospitals was conducted between March and August 2020. CAPA was defined using composite clinical criteria. Fine and Gray competing risks regression was used to analyze clinical outcomes and, multilevel mixed-effects ordinal logistic regression was used to compare longitudinal disease severity scores. RESULTS:In the cohort of 396 people, 39 met criteria for CAPA. Patients with CAPA were more likely than those without CAPA to have underlying pulmonary vascular disease (41% vs 21.6%, respectively; P = .01), liver disease (35.9% vs 18.2%; P = .02), coagulopathy (51.3% vs 33.1%; P = .03), solid tumors (25.6% vs 10.9%; P = .02), multiple myeloma (5.1% vs 0.3%; P = .03), and corticosteroid exposure during the index admission (66.7% vs 42.6%; P = .005), and had lower body mass indexes (median, 26.6 vs 29.9 [calculated as weight in kilograms divided by height in meters squared]; P = .04). Patients with CAPA had worse outcomes, as measured by ordinal severity of disease scores, requiring longer time to improvement (adjusted odds ratio, 1.081.091.1; P < .001), and advancing in severity almost twice as quickly (subhazard ratio, 1.31.82.5; P < .001). They were intubated twice as long as those without CAPA (subhazard ratio, 0.40.50.6; P < .001) and had longer hospital stays (median [interquartile range], 41.1 [20.5-72.4) vs 18.5 [10.7-31.8] days; P < .001). CONCLUSION:CAPA is associated with poor outcomes. Attention to preventive measures (screening and/or prophylaxis) is warranted in people with high risk of CAPA.

BACKGROUND:Medicaid expansion has led to earlier stage diagnoses in several cancers but has not been studied in hepatocellular carcinoma (HCC), a disease with complex risk factors. We examined the effect of Medicaid expansion on the diagnosis of HCC and associations with county-level social vulnerability. METHODS:Patients with HCC <65 years of age were identified from the SEER database (2010-2016). County-level social vulnerability factors were obtained from the CDC SVI and BRFSS. A Difference-in-Difference analysis evaluated change in early-stage diagnoses (stage I-II) between expansion and non-expansion states. A Difference-in-Difference-in-Difference analysis evaluated expansion impact among counties with higher proportions of social vulnerability. RESULTS:Of 19,751 patients identified, 81.5% were in expansion states. Uninsured status decreased in expansion states (6.3%-2.4%, p < 0.0001) and remained unchanged in non-expansion states (12.7%-14.8%, p = 0.43). There was no significant difference in the incidence of early-stage diagnoses between expansion states and non-expansion states. Results were consistent when accounting for social vulnerability. CONCLUSION/CONCLUSIONS:Medicaid expansion was not associated with earlier stage diagnoses in patients with HCC, including those with higher social vulnerability. Unlike other cancers, expanded access did not translate into higher utilization of care in HCC, suggesting barriers on a multitude of levels.

Background/UNASSIGNED:Posttransplant diabetes (PTD), a major complication after kidney transplantation (KT), is often attributable to immunosuppression. The risk of PTD may increase with more potent steroid maintenance and older recipient age. Methods/UNASSIGNED:Using United States Renal Data System data, we studied 12 488 adult first-time KT recipients (2010-2015) with no known pre-KT diabetes. We compared the risk of PTD among recipients who underwent early steroid withdrawal (ESW) versus continued steroid maintenance (CSM) using Cox regression with inverse probability weighting to adjust for confounding. We tested whether the risk of PTD resulting from ESW differed by recipient age (18-29, 30-54, and ≥55 y). Results/UNASSIGNED:). Conclusions/UNASSIGNED:The beneficial association of ESW with decreased PTD was more pronounced among recipients aged ≥55, supporting an age-specific assessment of the risk-benefit balance regarding ESW.