Faculty Bibliography

Introduction/UNASSIGNED:Depressive symptoms, even without a clinical diagnosis of depression, are common in kidney failure patients and may be a barrier to completing the complex process of kidney transplant (KT) evaluation. We assessed depressive symptom burden and association between depressive symptoms and access to KT waitlist by age. Methods/UNASSIGNED:In a prospective cohort of 3728 KT patients (aged 18-88 years), the Center for Epidemiologic Studies-Depression (CES-D) scale was used to measure depressive symptoms at evaluation. Depressive symptom severity was defined as follows: none: 0; minimal: 1 to 15; mild: 16 to 20; moderate: 21 to 25; severe: 26 to 60. Hazard ratios (HRs) of active listing within 1 year after evaluation were estimated using Cox proportional hazards models, adjusted for clinical and social factors. Results/UNASSIGNED: < 0.001). After adjustment, every 5-point higher CES-D score (more depressive symptoms) was associated with a 13% lower chance of listing (HR = 0.87, 95% CI: 0.85-0.90); the strongest association was found among patients aged ≥70 years (adjusted HR [aHR] = 0.73, 95% CI: 0.62-0.86). Furthermore, minimal (HR = 0.69, 95% CI: 0.60-0.79), mild (HR = 0.57, 95% CI: 0.44-0.72), moderate (HR = 0.53, 95% CI: 0.39-0.71), and severe (HR = 0.44, 95% CI: 0.34-0.57) depressive symptoms were all associated with a lower chance of listing. Conclusion/UNASSIGNED:Older candidates were less likely to report depressive symptoms at KT evaluation. Regardless of age, candidates who did report depressive symptoms, and even minimal symptoms, had a lower chance of listing. Transplant centers should routinely screen patients for depressive symptoms and refer the affected patients to mental health services to improve access to KT.

BACKGROUND:Hurricanes are severe weather events that can disrupt power, water, and transportation systems. These disruptions may be deadly for patients requiring maintenance dialysis. We hypothesized that the mortality risk among patients requiring maintenance dialysis would be increased in the 30 days after a hurricane. METHODS:Patients registered as requiring maintenance dialysis in the United States Renal Data System who initiated treatment between January 1, 1997 and December 31, 2017 in one of 108 hurricane-afflicted counties were followed from dialysis initiation until transplantation, dialysis discontinuation, a move to a nonafflicted county, or death. Hurricane exposure was determined as a tropical cyclone event with peak local wind speeds ≥64 knots in the county of a patient's residence. The risk of death after the hurricane was estimated using time-varying Cox proportional hazards models. RESULTS:The median age of the 187,388 patients was 65 years (IQR, 53-75) and 43.7% were female. There were 27 hurricanes and 105,398 deaths in 529,339 person-years of follow-up on dialysis. In total, 29,849 patients were exposed to at least one hurricane. Hurricane exposure was associated with a significantly higher mortality after adjusting for demographic and socioeconomic covariates (hazard ratio, 1.13; 95% confidence interval, 1.05-1.22). The association persisted when adjusting for seasonality. CONCLUSIONS:Patients requiring maintenance dialysis have a higher mortality risk in the 30 days after a hurricane.

BACKGROUND:Solid organ transplant recipients (SOTRs) are less likely to mount an antibody response to SARS-CoV-2 mRNA vaccines. Understanding risk factors for impaired vaccine response can guide strategies for antibody testing and additional vaccine dose recommendations. METHODS:Using a nationwide observational cohort of 1031 SOTRs, we created a machine learning model to explore, identify, rank, and quantify the association of 19 clinical factors with antibody responses to 2 doses of SARS-CoV-2 mRNA vaccines. External validation of the model was performed using a cohort of 512 SOTRs at Houston Methodist Hospital. RESULTS:Mycophenolate mofetil use, a shorter time since transplant, and older age were the strongest predictors of a negative antibody response, collectively contributing to 76% of the model's prediction performance. Other clinical factors, including transplanted organ, vaccine type (mRNA-1273 versus BNT162b2), sex, race, and other immunosuppressants, showed comparatively weaker associations with an antibody response. This model showed moderate prediction performance, with an area under the receiver operating characteristic curve of 0.79 in our cohort and 0.67 in the external validation cohort. An online calculator based on our prediction model is available at http://transplantmodels.com/covidvaccine/. CONCLUSIONS:Our machine learning model helps understand which transplant patients need closer follow-up and additional doses of vaccine to achieve protective immunity. The online calculator based on this model can be incorporated into transplant providers' practice to facilitate patient-centric, precision risk stratification and inform vaccination strategies among SOTRs.

BACKGROUND:Among adult kidney transplant (KT) candidates, 21% are frail and 55% have cognitive impairment, increasing the risk of pre- and post-KT mortality. Centers often assess frailty status and cognitive function during transplant evaluation to help identify appropriate candidate. Yet, there are no ethical guidelines regarding the use of frailty and cognitive function during this evaluation. We seek to develop a clinical consensus on balancing utility and justice in access to KT for frail and cognitively impaired patients. METHODS:Twenty-seven experts caring for ESRD patients completed a two-round Delphi panel designed to facilitate consensus (> 80% agreement). RESULTS:Experts believed that denying patients transplantation based solely on expected patient survival was inequitable to frail or cognitively impaired candidates; 100% agreed that frailty and cognitive impairment are important factors to consider during KT evaluation. There was consensus that health related quality of life and social support are important to consider before waitlisting frail or cognitively impaired patients. Experts identified important factors to consider before waitlisting frail (likely to benefit from KT, frailty reversibility, age, and medical contraindications) and cognitively impaired (degree of impairment and medication adherence) patients. CONCLUSIONS:Clinical experts believed it was ethically unacceptable to allocate organs solely based on patients' expected survival; frailty and cognitive impairment should be measured at evaluation when weighed against other clinical factors. Ethical guidelines regarding the use of frailty and cognitive function during KT evaluation ought to be developed.

BACKGROUND:Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared to the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥ 65) ESRD patients differed if they were treated for SHPT. METHODS:Using the United States Renal Data System (USRDS) and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006-2016. SHPT treatment was defined as use of vitamin D analogs, phosphate binders, calcimimetics, or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time varying exposure. RESULTS:Of 189 433 older ESRD adults, 92% had a claims diagnosis of SHPT, and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared to 11 cases per 100 person-years among untreated patients. Compared to untreated SHPT patients, the risk of dementia was 42% lower (aHR = 0.58, 95% CI: 0.56-0.59) among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (pinteraction = 0.02) and race (pinteraction ≤ 0.01) with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having greatest reduction in dementia risk. CONCLUSION/CONCLUSIONS:Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for treatment of SHPT in older ESRD patients.