Faculty Bibliography

Background/UNASSIGNED:Variation in the use of immunosuppression regimens after liver transplant has not been well described. Methods/UNASSIGNED:Immunosuppression regimens used after liver transplant were identified in a novel database integrating national transplant registry and pharmacy fill records for 24 238 recipients (2006-2014). Bilevel hierarchical models were developed to quantify the effects of transplant program, recipient, and donor characteristics on regimen choice. Results/UNASSIGNED:=0.003). Conclusions/UNASSIGNED:Liver transplant immunosuppression is dominantly driven by program preference, but case factors also affect regimen choice. This variation frames a natural experiment for future evaluations of comparative efficacy.

BACKGROUND AND OBJECTIVES:Older patients with ESKD experience rapid declines in executive function after initiating hemodialysis; these impairments might lead to high rates of dementia and Alzheimer's disease in this population. We estimated incidence, risk factors, and sequelae of diagnosis with dementia and Alzheimer's disease among older patients with ESKD initiating hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We studied 356,668 older (age ≥66 years old) patients on hemodialysis (January 1, 2001 to December 31, 2013) from national registry data (US Renal Data System) linked to Medicare. We estimated the risk (cumulative incidence) of diagnosis of dementia and Alzheimer's disease and studied factors associated with these disorders using competing risks models to account for death, change in dialysis modality, and kidney transplant. We estimated the risk of subsequent mortality using Cox proportional hazards models. RESULTS:The 1- and 5-year risks of diagnosed dementia accounting for competing risks were 4.6% and 16% for women, respectively, and 3.7% and 13% for men, respectively. The corresponding Alzheimer's disease diagnosis risks were 0.6% and 2.6% for women, respectively, and 0.4% and 2.0% for men, respectively. The strongest independent risk factors for diagnosis of dementia and Alzheimer's disease were age ≥86 years old (dementia: hazard ratio, 2.11; 95% confidence interval, 2.04 to 2.18; Alzheimer's disease: hazard ratio, 2.11; 95% confidence interval, 1.97 to 2.25), black race (dementia: hazard ratio, 1.70; 95% confidence interval, 1.67 to 1.73; Alzheimer's disease: hazard ratio, 1.78; 95% confidence interval, 1.71 to 1.85), women (dementia: hazard ratio, 1.10; 95% confidence interval, 1.08 to 1.12; Alzheimer's disease: hazard ratio, 1.12; 95% confidence interval, 1.08 to 1.16), and institutionalization (dementia: hazard ratio, 1.36; 95% confidence interval, 1.33 to 1.39; Alzheimer's disease: hazard ratio, 1.10; 95% confidence interval, 1.05 to 1.15). Older patients on hemodialysis with a diagnosis of dementia were at 2.14-fold (95% confidence interval, 2.07 to 2.22) higher risk of subsequent mortality; those with a diagnosis of Alzheimer's disease were at 2.01-fold (95% confidence interval, 1.89 to 2.15) higher mortality risk. CONCLUSIONS:Older patients on hemodialysis are at substantial risk of diagnosis with dementia and Alzheimer's disease, and carrying these diagnoses is associated with a twofold higher mortality.

Depressive symptoms and frailty are each independently associated with morbidity and mortality in kidney transplant (KT) recipients. We hypothesized that having both depressive symptoms and frailty would be synergistic and worse than the independent effect of each. In a multicenter cohort study of 773 KT recipients, we measured the Fried frailty phenotype and the modified 18-question Center for Epidemiologic Studies-Depression Scale (CES-D). Using adjusted Poisson regression and survival analysis, we tested whether depressive symptoms (CES-D score > 14) and frailty were associated with KT length of stay (LOS), death-censored graft failure (DCGF), and mortality. At KT admission, 10.0% of patients exhibited depressive symptoms, 16.3% were frail, and 3.6% had both. Recipients with depressive symptoms were more likely to be frail (aOR = 3.97, 95% CI: 2.28-6.91, P < 0.001). Recipients with both depressive symptoms and frailty had a 1.88 times (95% CI: 1.70-2.08, P < 0.001) longer LOS, 6.20-fold (95% CI:1.67-22.95, P < 0.01) increased risk of DCGF, and 2.62-fold (95% CI:1.03-6.70, P = 0.04) increased risk of mortality, compared to those who were nonfrail and without depressive symptoms. There was only evidence of synergistic effect of frailty and depressive symptoms on length of stay (P for interaction < 0.001). Interventions aimed at reducing pre-KT depressive symptoms and frailty should be explored for their impact on post-KT outcomes.

BACKGROUND:Health-related quality of life (HRQOL) reflects a patient's perceived disease burden, treatment effectiveness, and health status. Given the time burden and physiologic effects of hemodialysis, patients who spend dialysis time (9-15 h/week) physically or intellectually engaged may have better HRQOL. We characterized the intradialytic activities and explored their association with HRQOL. METHODS:In a cross-sectional study of 431 hemodialysis patients, we ascertained kidney-disease-specific quality of life, measured frailty, and surveyed participants about their usual active intradialytic activities (reading, playing games, doing puzzles, chatting, or other) and passive intradialytic activities (watching TV or sleeping). We used adjusted ordered logistic regression to identify correlates of the activity index (the sum of active intradialytic activities) and adjusted linear regression to quantify the association between the activity index and physical-, mental-, and kidney-disease-specific HRQOL. RESULTS:The 2 most common intradialytic activities were passive activities (watching TV = 87.9%; sleeping = 72.4%). Participants who were female (aOR 1.85, 95% CI 1.28-2.66; p = 0.001), nonfrail (aOR 1.70, 95% CI 1.06-2.70; p = 0.03), and nonsmokers (aOR 2.61, 95% CI 1.39-4.90; p = 0.003) had a higher intradialytic activity index after adjustment. Higher intradialytic activity index was associated with better mental- (0.83 points, 95% CI 0.04-1.62; p = 0.04) and kidney-disease-specific HRQOL (1.70 points, 95% CI 0.47-2.93; p = 0.007), but not physical HRQOL. CONCLUSIONS:Hemodialysis patients with more active intradialytic activities report better mental and kidney-disease-specific HRQOL. These results should be confirmed in a prospective study with a broader cohort of hemodialysis patients. Dialysis providers may consider offering patients with low levels of activity additional support and opportunities to engage in beneficial intradialytic activities.

BACKGROUND:Up to 31% of kidney transplant (KT) recipients experience early hospital readmission (EHR). We hypothesized that EHR among older KT recipients is higher than younger recipients due to increased comorbidities and higher prevalence of frailty. METHODS:We identified 22,458 older (age ≥65) and 86,372 younger (18 to < 65) first-time KT recipients (December 1, 1999 - December 31, 2014) using United States Renal Data System data. We estimated the association between patient-level characteristics and EHR (30 days post-KT discharge) with modified Poisson regression among older and younger KT recipients, separately. We estimated the association between graft loss and mortality and EHR using Cox proportional hazards. RESULTS:EHR was more common in older KT recipients (30.1 vs. 27.6%; p < 0.001). Risk factors for EHR that differed by recipient age included female sex, African American race, diabetes, smoking, dialysis vintage, donor age, and length of stay. Risk of graft loss associated with EHR was greater among older KT recipients (adjusted hazard ratio [aHR] 1.64, 95% CI 1.51-1.77, p < 0.001) than younger KT recipients (aHR 1.43, 95% CI 1.38-1.48, p < 0.001; interaction p < 0.01). However, the risk of mortality associated with EHR was greater among younger recipients (aHR 1.52, 95% CI 1.47-1.57, p < 0.001) than that in older -recipients (aHR 1.40, 95% CI 1.34-1.47, p < 0.001; interaction p < 0.01). CONCLUSIONS:Older KT recipients are more likely to experience EHR and are at a higher risk of graft loss after EHR than younger recipients. Targeted interventions to prevent EHR and subsequent graft loss in this population should be identified.

OBJECTIVES:To explore trends in liver transplantation (LT) and outcomes for older recipients for evaluation, counseling, and appropriate referral of this vulnerable group of older adults. DESIGN:Prospective national cohort study. SETTING:Scientific Registry of Transplant Recipients (January 1, 2003-December 31, 2016). PARTICIPANTS:Older (aged ≥ 65) deceased donor liver-only transplant recipients (n=8,627). MEASUREMENTS:We evaluated temporal changes in recipient, donor, and transplant characteristics and post-LT length of stay (LOS), acute rejection, graft loss, and mortality using logistic regression and Cox proportional hazards. RESULTS:LT in older adults almost quadrupled, from 263 in 2003 (9.5% of total LTs that year) to 1,144 in 2016 (20.7% of total LTs). Recent recipients were more likely to be female and African American and have a higher body mass index and Model for End-Stage Liver Disease score. Hepatitis C, nonalcoholic steatohepatitis, and hepatocellular carcinoma were the most common indications for LT in recent recipients. Odds of LOS longer than 2 weeks decreased 34% from 2003-06 to 2013-16 (adjusted odds ratio (aOR)=0.66, 95% confidence interval (CI)=0.57-0.76, P < .001), 1-year acute rejection decreased 30% (aOR=0.70, 95% CI=0.56-0.88, P = .002), all-cause graft loss decreased 54% (adjusted hazard ratio (aHR)=0.46, 95% CI=0.40-0.52, P < .001), and mortality decreased 57% (aHR=0.43, 95% CI=0.38-0.49, P < .001). CONCLUSION:Despite the substantial increase in the number of older adults undergoing LT and the severity of their condition, LOS, rejection, graft loss, and mortality have significantly decreased over time. These trends can help guide appropriate LT referral and counseling in older adults with end-stage liver disease. J Am Geriatr Soc 66:2321-2326, 2018.

BACKGROUND:Few objective tests can be performed at admission for kidney transplantation [KT] to discern risk of increased length of stay [LOS], which is important for patient counseling and is associated with increased costs and mortality. The short physical performance battery [SPPB] is an easily administered, potentially modifiable, 3-part test of lower extremity function. SPPB score is associated with longer hospital LOS in older adults, and may provide similar utility in KT recipients given that ESRD is a disease of accelerated aging. The aim of this study was to characterize the association between SPPB-derived lower extremity function and LOS. METHODS:The SPPB was administered at KT admission in a prospective cohort of 595 recipients (8/2009-6/2016). The independent association between SPPB impairment (score ≤ 10) and LOS was tested with an adjusted conventional generalized gamma parametric survival model. RESULTS:Impaired recipients experienced longer LOS (median: 10 vs. 8 days; P <  0.001) with the greatest difference in percent discharged on day 10 (impaired: 54.5%, unimpaired: 73.3%). Discharge typically took 13% longer in the impaired group (relative time = 1.13; 95%CI: 1.05, 1.21, P = 0.001). Discharge for impaired recipients compared to unimpaired was least likely at day 5 (hazard ratio = 0.71; 95% CI:0.68, 0.74, P <  0.001). No differences in the SPPB impairment-LOS relationship were found by age (interaction P = 0.74). CONCLUSIONS:Pre-KT SPPB impairment was independently associated with longer LOS regardless of age, indicating that it is a useful, objective tool for pre-KT risk assessment in younger and older recipients that may help inform discharge planning.