Faculty Bibliography

BACKGROUND:Approximately half of the patients who progress to end-stage kidney disease (ESKD) and undergo dialysis develop difficulties carrying out essential self-care activities, leading to institutionalization and mortality. It is unclear what percentage of kidney transplant (KT) candidates, a group of ESKD patients selected to be healthy enough to withstand transplantation, are functionally independent and whether independence is associated with better access to KT and reduced waitlist mortality. METHODS:We studied a prospective cohort of 3168 ESKD participants (January 2009 to June 2018) who self-reported functional independence in more basic self-care Activities of Daily Living (ADL) (needing help with eating, dressing, walking, grooming, toileting and bathing) and more complex instrumental ADL (IADL) (needing help using a phone, shopping, cooking, housework, washing, using transportation, managing medications and managing money). We estimated adjusted associations between functional independence (separately) and listing (Cox), waitlist mortality (competing risks) and transplant rates (Poisson). RESULTS:At KT evaluation, 92.4% were independent in ADLs, but only 68.5% were independent in IADLs. Functionally independent participants had a higher chance of listing for KT [ADL: adjusted hazard ratio (aHR) = 1.55, 95% confidence interval (CI) 1.30-1.87; IADL: aHR = 1.39, 95% CI 1.26-1.52]. Among KT candidates, ADL independence was associated with lower waitlist mortality risk [adjusted subdistribution HR (aSHR) = 0.66, 95% CI 0.44-0.98] and higher rate of KT [adjusted incidence rate ratio (aIRR) = 1.58, 95% CI 1.12-2.22]; the same was not observed for IADL independence (aSHR = 0.86, 95% CI 0.65-1.12; aIRR = 1.01, 95% CI 0.97-1.19). CONCLUSIONS:Functional independence in more basic self-care ADL was associated with better KT access and lower waitlist mortality. Nephrologists, geriatricians and transplant surgeons should screen KT candidates for ADLs, and identify interventions to promote independence and improve waitlist outcomes.

In this review we summarize the research pertaining to the role of exercise in preventing cognitive decline in patients with end-stage kidney disease (ESKD). Impairment in cognitive function, especially in executive function, is common in patients with ESKD, and may worsen with maintenance dialysis as a result of retention of uremic toxins, recurrent cerebral ischemia, and high burden of inactivity. Cognitive impairment may lead to long-term adverse consequences, including dementia and death. Home-based and intradialytic exercise training (ET) are among the nonpharmacologic interventions identified to preserve cognitive function in ESKD. Additionally, cognitive training (CT) is an effective approach recently identified in this population. While short-term benefits of ET and CT on cognitive function were consistently observed in patients undergoing dialysis, more studies are needed to replicate these findings in diverse populations including kidney transplant recipients with long-term follow-up to better understand the health and quality of life consequences of these promising interventions. ET as well as CT are feasible interventions that may preserve or even improve cognitive function for patients with ESKD. Whether these interventions translate to improvements in quality of life and long-term health outcomes, including dementia prevention and better survival, are yet to be determined.

Epidemiology should aim to improve population health; however, no consensus exists regarding the activities and skills that should be prioritized to achieve this goal. We performed a scoping review of articles addressing the translation of epidemiologic knowledge into improved population health outcomes. We identified 5 themes in the translational epidemiology literature: foundations of epidemiologic thinking, evidence-based public health or medicine, epidemiologic education, implementation science, and community-engaged research (including literature on community-based participatory research). We then identified 5 priority areas for advancing translational epidemiology: 1) scientific engagement with public health; 2) public health communication; 3) epidemiologic education; 4) epidemiology and implementation; and 5) community involvement. Using these priority areas as a starting point, we developed a conceptual framework of translational epidemiology that emphasizes interconnectedness and feedback among epidemiology, foundational science, and public health stakeholders. We also identified 2-5 representative principles in each priority area that could serve as the basis for advancing a vision of translational epidemiology. We believe an emphasis on translational epidemiology can help the broader field to increase the efficiency of translating epidemiologic knowledge into improved health outcomes and to achieve its goal of improving population health.

AIM/OBJECTIVE:There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear. METHODS:Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight. RESULTS:Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03). CONCLUSION/CONCLUSIONS:Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.

Background:Frail obese community-dwelling older adults are at increased mortality risk. Among hemodialysis (HD) patients, frailty is common and associated with increased mortality risk; however, in dialysis, obesity is associated with decreased mortality risk. Whether the frail-obese phenotype is associated with increased mortality risk among HD patients remains unclear. Methods:This study included 370 incident HD patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. We measured frailty using the Fried phenotype, general obesity [body mass index (BMI) ≥30 kg/m2] and abdominal obesity [waist:hip ratio (WHR) ≥median WHR] and estimated their associations with mortality. Results:The mean age was 55 years, with 42% female, 73% African American, 57% diabetic and 52% frail. Frail HD patients had higher mean BMI (frail = 30.3 kg/m2, non-frail = 28.3 kg/m2; P = 0.02) and similar WHR (P = 0.8). Twenty-two percent were frail with general obesity and 27% were frail with abdominal obesity. Frailty was associated with 1.66-fold increased mortality risk [95% confidence interval (CI) 1.03-2.67]. BMI was associated with a decreased mortality risk [25.0-29.9 kg/m2 hazard ratio (HR) 0.53 (95% CI 0.31-0.93); ≥30 kg/m2 HR 0.34 (95% CI 0.19-0.62)]. Frailty was associated with elevated mortality risk among HD patients with general [HR 3.77 (95% CI 1.10-12.92)] and abdominal obesity [HR 2.38 (95% CI 1.17-4.82)]. Frailty was not associated with mortality among HD patients without general or abdominal obesity. Conclusions:In adults initiating HD, frailty was associated with elevated mortality risk, even among the obese. Frail-obese HD patients may be a high-risk, often-overlooked population, as obesity is assumed to be protective. Measurement of frailty and obesity may facilitate risk stratification.

More than one-third of US adults have limited health literacy, putting them at risk of adverse clinical outcomes. We evaluated the prevalence of limited health literacy among 1578 adult kidney transplant (KT) candidates (May 2014-November 2017) and examined its association with listing for transplant and waitlist mortality in this pilot study. Limited health literacy was assessed at KT evaluation by using a standard cutoff score ≤5 on the Brief Health Literacy Screen (score range 0-12, lower scores indicate worse health literacy). We used logistic regression and adjusted Cox proportional hazards models to identify risk factors for limited health literacy and to quantify its association with listing and waitlist mortality. We found that 8.9% of candidates had limited health literacy; risk factors included less than college education (adjusted odds ratio [aOR] = 2.87, 95% confidence interval [CI]:1.86-4.43), frailty (aOR = 1.85, 95% CI:1.22-2.80), comorbidity (Charlson comorbidity index [1-point increase] aOR = 1.12, 95% CI: 1.04-1.20), and cognitive impairment (aOR = 3.45, 95% CI: 2.20-5.41) after adjusting for age, sex, race, and income. Candidates with limited health literacy had a 30% (adjusted hazard ratio = 0.70, 95% CI: 0.54-0.91) decreased likelihood of listing and a 2.42-fold (95% CI: 1.16- to 5.05-fold) increased risk of waitlist mortality. Limited health literacy may be a salient mechanism in access to KT; programs to aid candidates with limited health literacy may improve outcomes and reduce disparities.

BACKGROUND:Cognitive impairment is common in patients with end-stage renal disease and is associated with poor outcomes on dialysis. We hypothesized that cognitive impairment might be associated with an increased risk of all-cause graft loss (ACGL) in kidney transplant (KT) recipients. METHODS:Using the Modified Mini-Mental State (3MS) examination, we measured global cognitive function at KT hospital admission in a prospective, 2-center cohort of 864 KT candidates (August 2009 to July 2016). We estimated the association between pre-KT cognitive impairment and ACGL using Cox regression, adjusting for recipient, donor, and transplant factors. RESULTS:In living donor KT (LDKT) recipients, the prevalence was 3.3% for mild impairment (60 ≤ 3MS < 80) and 3.3% for severe impairment (3MS < 60). In deceased donor KT (DDKT) recipients, the prevalence was 9.8% for mild impairment and 2.6% for severe impairment. The LDKT recipients with cognitive impairment had substantially higher ACGL risk than unimpaired recipients (5-year ACGL: 45.5% vs 10.6%; P < 0.01; adjusted hazard ratio [aHR] any impairment, 5.40 (95% confidence interval [CI], 1.78-16.34; P < 0.01); aHR severe impairment, 5.57 (95% CI, 1.29-24.00; P = 0.02). Similarly, DDKT recipients with severe impairment had higher ACGL risk than recipients without severe impairment (5-year ACGL, 53.0% vs 24.2%; P = 0.04); aHR severe impairment, 2.92 (95% CI, 1.13-7.50; P = 0.03). CONCLUSIONS:Given the elevated risk of ACGL among KT recipients with cognitive impairment observed in this 2-center cohort, research efforts should explore the mechanisms of graft loss and mortality associated with cognitive impairment and identify potential interventions to improve posttransplant survival.

Low T cell counts and acute rejection are associated with increased cardiovascular events (CVEs); T cell-depleting agents decrease both. Thus, we aimed to characterize the risk of CVEs by using an induction agent used in kidney transplant recipients. We conducted a secondary data analysis of patients who received a kidney transplant and used Medicare as their primary insurance from 1999 to 2010. Outcomes of interest were incident CVE, all-cause mortality, CVE-related mortality, and a composite outcome of mortality and CVE. Of 47 258 recipients, 29.3% received IL-2 receptor antagonist (IL-2RA), 33.3% received anti-thymocyte globulin (ATG), 7.3% received alemtuzumab, and 30.0% received no induction. Compared with IL-2RA, there was no difference in the risk of CVE in the ATG (adjusted hazard ratio [aHR] 0.98, 95% confidence interval [CI] 0.92-1.05) and alemtuzumab group (aHR 1.01, 95% CI 0.89-1.16), but slightly higher in the no induction group (aHR 1.06, 95% CI 1.00-1.14). Acute rejection did not modify this association in the latter group but did increase CVE by 46% in the alemtuzumab group. There was no difference in the hazard of all-cause or CVE-related mortality. Only in the ATG group, a 7% lower hazard of the composite outcome of mortality and CVE was noted. Induction agents are not associated with incident CVE, although prospective trials are needed to determine a personalized approach to prevention.