Faculty Bibliography

Frailty is a multidimensional condition and is the result of the body's age-associated decline in physical, cognitive, physiological, and immune reserves. The aim of this systematic review is to assess the quality of evidence of the included studies, determine the prevalence of frailty among kidney transplant candidates, and evaluate the relationship between frailty and associated patient characteristics and outcomes after kidney transplantation.

BACKGROUND:Individuals undergoing hemodialysis in the United States frequently report pain and receive three-fold more opioid prescriptions than the general population. While opioid use is appropriate for select patients, high-dose utilization may contribute to an increased risk of death due to possible accumulation of opioid metabolites. METHODS:We studied high-dose opioid utilization (≥120 morphine milligram equivalents [MME] per day) among adults initiating hemodialysis in the United States between 2007 and 2014 using national registry data. We calculated the cumulative incidence (%) of high-dose utilization and depicted trends in the average percentage of days individuals were exposed to opioids. We used adjusted Cox proportional hazards models to identify which opioid doses were associated with mortality. RESULTS:Among 327,344 adults undergoing hemodialysis, the cumulative incidence of high-dose utilization was 14.9% at 2 years after initiating hemodialysis. Among patients with ≥1 opioid prescription during follow-up, the average percentage of days exposed to high-dose utilization increased from 13.9% in 2007 to 26.1% in 2014. Compared to 0MME per day, doses < 60MME were not associated with an increased risk of mortality, but high-dose utilization was associated with a 1.63-fold (95% CI, 1.57, 1.69) increased risk of mortality. The risk of mortality associated with opioid dose was highest in the first year after hemodialysis initiation. CONCLUSIONS:The risk of mortality associated with opioid utilization among individuals on hemodialysis increases as doses exceed 60MME per day and is greatest during periods of high-dose utilization. Patients and clinicians should carefully weigh the risks and benefits of opioid doses exceeding 60MME per day.

Importance:Historically, deceased organ donation was lower among Black compared with White populations, motivating efforts to reduce racial disparities. The overarching effect of these efforts in Black and other racial/ethnic groups remains unclear. Objective:To examine changes in deceased organ donation over time. Design, Setting, and Participants:This population-based cohort study used data from January 1, 1999, through December 31, 2017, from the Scientific Registry of Transplant Recipients to quantify the number of actual deceased organ donors, and from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Detailed Mortality File to quantify the number of potential donors (individuals who died under conditions consistent with organ donation). Data were analyzed from December 2, 2019, to May 14, 2020. Exposures:Race and ethnicity of deceased and potential donors. Main Outcomes and Measures:For each racial/ethnic group and year, a donation ratio was calculated as the number of actual deceased donors divided by the number of potential donors. Direct age and sex standardization was used to allow for group comparisons, and Poisson regression was used to quantify changes in donation ratio over time. Results:A total of 141 534 deceased donors and 5 268 200 potential donors were included in the analysis. Among Black individuals, the donation ratio increased 2.58-fold from 1999 to 2017 (yearly change in adjusted incidence rate ratio [aIRR], 1.05; 95% CI, 1.05-1.05; P < .001). This increase was significantly greater than the 1.60-fold increase seen in White individuals. Nevertheless, substantial racial differences remained, with Black individuals still donating at only 69% the rate of White individuals in 2017 (P < .001). Among other racial minority populations, changes were less drastic. Deceased organ donation increased 1.80-fold among American Indian/Alaska Native and 1.40-fold among Asian or Pacific Islander populations, with substantial racial differences remaining in 2017 (American Indian/Alaska Native population donation at 28% and Asian/Pacific Islander population donation at 85% the rate of the White population). Deceased organ donation differences between Hispanic/Latino and non-Hispanic/Latino populations increased over time (4% lower in 2017). Conclusions and Relevance:The findings of this cohort study suggest that differences in deceased organ donation between White and some racial minority populations have attenuated over time. The greatest gains were observed among Black individuals, who have been the primary targets of study and intervention. Despite improvements, substantial differences remain, suggesting that novel approaches are needed to understand and address relatively lower rates of deceased organ donation among all racial minorities.

Allografts from living kidney donors with hypertension may carry subclinical kidney disease from the donor to the recipient and, thus, lead to adverse recipient outcomes. We examined eGFR trajectories and all-cause allograft failure in recipients from donors with versus without hypertension, using mixed-linear and Cox regression models stratified by donor age. We studied a US cohort from 1/1/2005 to 6/30/2017; 49 990 recipients of allografts from younger (<50 years old) donors including 597 with donor hypertension and 21 130 recipients of allografts from older (≥50 years old) donors including 1441 with donor hypertension. Donor hypertension was defined as documented predonation use of antihypertensive therapy. Among recipients from younger donors with versus without hypertension, the annual eGFR decline was -1.03 versus -0.53 ml/min/m² (P = 0.002); 13-year allograft survival was 49.7% vs. 59.0% (adjusted allograft failure hazard ratio [aHR] 1.23; 95% CI 1.05-1.43; P = 0.009). Among recipients from older donors with versus without hypertension, the annual eGFR decline was -0.67 versus -0.66 ml/min/m² (P = 0.9); 13-year allograft survival was 48.6% versus 52.6% (aHR 1.05; 95% CI 0.94-1.17; P = 0.4). In secondary analyses, our inferences remained similar for risk of death-censored allograft failure and mortality. Hypertension in younger, but not older, living kidney donors is associated with worse recipient outcomes.

During the COVID-19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case-by-case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high-risk transplantations. For induction, 26.5% were less likely to give T-cell depletion and 14.8% were more likely to give non-depleting agents. These practices varied by program-level factors more so than the COVID-19 burden. In patients with mild, moderate and severe COVID-19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti-metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID-19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti-metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high-risk transplants and increased maintenance steroids. The long-term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.