Faculty Bibliography

BACKGROUND:The risk of cardiovascular mortality is high among adults with end-stage renal disease (ESRD) undergoing hemodialysis. Waist-to-hip ratio (WHR), a metric of abdominal adiposity, is a predictor of cardiovascular disease (CVD) and mortality in the general population; however, no studies have examined the association with CVD mortality, particularly sudden cardiac death (SCD), in incident hemodialysis. METHODS:Among 379 participants incident (< 6 months) to hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD study, we evaluated associations between WHR and risk of CVD mortality, SCD, and non-CVD mortality in Cox proportional hazards regression models. RESULTS:At study enrollment, mean age was 55 years with 41% females, 73% African Americans, and 57% diabetics. Mean body mass index was 29.3 kg/m2, and mean WHR was 0.95. During a median follow-up time of 2.5 years, there were 35 CVD deaths, 15 SCDs, and 48 non-CVD deaths. Every 0.1 increase in WHR was associated with higher risk (hazard ratio [95% CI]) of CVD mortality (1.75 [1.06-2.86]) and SCD (2.45 [1.20-5.02]), but not non-CVD mortality (0.93 [0.59-1.45]), independently of demographics, body mass index, comorbidities, inflammation, and traditional CVD risk factors. CONCLUSIONS:WHR is significantly associated with CVD mortality including SCD, independently of other CVD risk factors in incident hemodialysis. This simple, easily obtained bedside metric may be useful in dialysis patients for CVD risk stratification.

Background/UNASSIGNED:Individuals with chronic kidney disease (CKD) have low levels of physical activity and physical function. Although guidelines endorse exercise counseling for individuals with CKD, it is not yet part of routine care. Objective/UNASSIGNED:We investigated the effect of attending a real-life exercise counseling clinic (ECC) on physical function in individuals with CKD. Design/UNASSIGNED:Retrospective analysis of prospectively collected observational data with quasi-experimental design. Setting and Participants/UNASSIGNED:Patients with all stages of CKD registered in a large provincial renal program were eligible. The exposed cohort who attended the ECC between January 1, 2011, and March 15, 2014, included 214 individuals. The control cohort included 292 individuals enrolled in an observational study investigating longitudinal change in frailty during the same time period. Predictor/Factor/UNASSIGNED:Attendance at an ECC. Outcomes and Measurements/UNASSIGNED:Change in physical function as measured by Short Physical Performance Battery (SPPB) score, physical activity level (Human Activity Profile [HAP]/Physical Activity Scale for the Elderly [PASE]), and health-related quality of life (HRQOL; EQ5D/VAS) over 1 year. Results/UNASSIGNED:= .72). There was no significant difference in the proportion of individuals in each cohort with an increase/decrease in SPPB score over time. There was no significant change in physical activity or HRQOL over time between groups. Limitations/UNASSIGNED:Quasi-experimental design, low rate of follow-up attendance. Conclusions/UNASSIGNED:In this pragmatic study, exercise counseling had no significant effect on change in SPPB score, suggesting that a single exercise counseling session alone is inadequate to improve physical function in CKD.

OBJECTIVE:To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and mortality. BACKGROUND:Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality. METHODS:We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOS: negative binomial regression; LOS ≥2 weeks: logistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis). RESULTS:Frailty was independently associated with longer LOS [relative risk = 1.15, 95% confidence interval (CI): 1.03-1.29; P = 0.01] and LOS ≥2 weeks (odds ratio = 1.57, 95% CI: 1.06-2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI: 1.30-1.86; P < 0.001; frail hazard rate = 0.97, 95% CI: 0.79-1.19, P = 0.80; P for interaction = 0.001). CONCLUSIONS:Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.

BACKGROUND:There is increasing evidence questioning the use of warfarin for atrial fibrillation (AF) among older adults with end stage renal disease (ESRD). We assessed the patterns and determinants of warfarin utilization among these patients in the US. METHODS:We assembled a cohort of older adults (age ≥65) undergoing dialysis with incident AF from July 2007 to November 2011 from the US Renal Data System (USRDS). We used descriptive statistics to characterize warfarin utilization within 30 days of AF discharge, and logistic regression to quantify patient characteristics associated with warfarin initiation. RESULTS:Among 5730 older adults undergoing dialysis with incident AF, 15.5% initiated warfarin. Among 2906 patients with high risk of bleeding, 12.7% initiated warfarin; whereas 14.9% initiated warfarin among 4824 patients with high risk of stroke. After adjustment for patient characteristics, warfarin initiation was lower among patients who were older [odds ratio (OR) = 0.74 per 10-year increase, 95% confidence interval (CI) 0.66-0.83] and those with a history of diabetes (OR = 0.75, 95% CI 0.63-0.90), myocardial infarction (OR = 0.64, 95% CI 0.50-0.80), or bleeding (OR = 0.63, 95% CI 0.50-0.80). There was no association between sex, race, or dialysis modality and warfarin initiation. Among patients who initiated warfarin, 46.8% discontinued warfarin use after a median treatment length of 8.6 months. CONCLUSION/CONCLUSIONS:Despite the unclear benefit and increased bleeding risk of warfarin treatment in patients with ESRD, 1 in 8 older adults undergoing dialysis with incident AF in the US who had high risk of bleeding used warfarin. Changes to warfarin therapy due to discontinuation were common after initiation.

BACKGROUND:After kidney transplantation, early readmission is independently associated with graft loss and mortality. The mechanism of this association is poorly understood. Understanding the timeline of risk, that is, during the readmission hospitalization versus periods postreadmission, will provide additional insights. METHODS:We used national registry data to study 56 076 adult Medicare-primary first-time kidney transplant recipients from December 1999 to October 2011. Piecewise Cox proportional hazard models were used to estimate the association between graft loss, mortality, and readmission for 2 periods: readmission hospitalization and postreadmission. RESULTS:During the readmission hospitalization, graft loss was substantially higher (deceased donor kidney transplant [DDKT] without delayed graft function [DGF] hazard ratio: 24.634.447.9, P < 0.001; with DGF: 10.815.221.4, P < 0.001; live donor kidney transplant [LDKT]: 18.136.774.2, P < 0.001) and mortality was substantially higher (DDKT without DGF: 14.120.830.7, P < 0.001; with DGF: 9.0312.818.0, P < 0.001; LDKT: 9.0018.241.3, P < 0.001). Immediately after readmission discharge, graft loss (DDKT without DGF: 2.082.402.77, P < 0.001; with DGF: 1.832.142.51, P < 0.001; LDKT: 2.002.503.13, P < 0.001), and mortality (DDKT without DGF: 2.162.432.73, P < 0.001; with DGF: 1.832.162.88, P < 0.001; LDKT: 1.902.342.88, P < 0.001) remained elevated, but much less so. After readmission, the hazard of graft loss remained, but decreased 19% per year for DDKT recipients (time varying coefficient 0.780.810.85, P < 0.001) and 14% per year for LDKT recipients (0.790.860.93, P < 0.001). The hazard of mortality remained, but decreased 14% per year for DDKT recipients (0.830.860.89, P < 0.001) and 9% per year for LDKT recipients (0.850.910.98, P < 0.001). CONCLUSIONS:In conclusion, readmission is most strongly associated with graft loss and mortality during the readmission hospitalization, but also portends a lasting, albeit attenuated, risk postreadmission.

BACKGROUND:Frailty increases early hospital readmission and mortality risk among kidney transplantation (KT) recipients. Although frailty represents a high-risk state for this population, the correlates of frailty, the patterns of the 5 frailty components, and the risk associated with these patterns are unclear. METHODS:Six hundred sixty-three KT recipients were enrolled in a cohort study of frailty in transplantation (12/2008-8/2015). Frailty, activities of daily living (ADL)/instrumental ADL (IADL) disability, Centers for Epidemiologic Studies Depression Scale depression, education, and health-related quality of life (HRQOL) were measured. We used multinomial regression to identify frailty correlates. We identified which patterns of the 5 components were associated with mortality using adjusted Cox proportional hazards models. RESULTS:Frailty prevalence was 19.5%. Older recipients (adjusted prevalence ratio [PR], 2.22; 95% confidence interval [CI], 1.21-4.07) were more likely to be frail. The only other factors that were independently associated with frailty were IADL disability (PR, 3.22; 95% CI, 1.72-6.06), depressive symptoms (PR, 11.31; 95% CI, 4.02-31.82), less than a high school education (PR, 3.10; 95% CI, 1.30-7.36), and low HRQOL (fair/poor: PR, 3.71; 95% CI, 1.48-9.31). The most common pattern was poor grip strength, low physical activity, and slowed walk speed (19.4%). Only 2 patterns of the 5 components emerged as having an association with post-KT mortality. KT recipients with exhaustion and slowed walking speed (hazards ratio = 2.43; 95% CI, 1.17-5.03) and poor grip strength, exhaustion, and slowed walking speed (hazard ratio, 2.61; 95% CI, 1.14-5.97) were at increased mortality risk. CONCLUSIONS:Age was the only conventional factor associated with frailty among KT recipients; however, factors rarely measured as part of clinical practice, namely, HRQOL, IADL disability, and depressive symptoms, were significant correlates of frailty. Redefining the frailty phenotype may be needed to improve risk stratification for KT recipients.

Older patients with ESRD who receive a kidney transplant (KT) may develop post-KT dementia and Alzheimer's disease (AD) associated with their long-standing kidney disease and/or neurotoxic immunosuppressant agents. To investigate this possibility, we studied 40,918 older (aged ≥55 years) KT recipients (January 1, 1999 to December 31, 2011) linked to Medicare claims through the US Renal Data System. We estimated dementia and AD risk (cumulative incidence) and studied factors associated with these sequelae using competing risks models. We estimated the risk of death-censored graft loss and mortality after developing dementia or the AD subtype of dementia, separately, using adjusted Cox proportional hazards models. Older recipients had a 10-year dementia risk ranging from 5.1% for recipients aged 55-60 years to 17.0% for recipients aged ≥75 years; 10-year AD risk ranged from 1.0% to 6.7%, respectively. The strongest predictors for dementia and AD were older recipient age and pretransplant diabetes. The 10-year graft loss risk was 28.8% for those who did not develop dementia and 43.1% for those who did, and the corresponding mortality risks were 55.7% and 89.9%, respectively. Older recipients with dementia had a 1.52-fold (95% confidence interval, 1.39 to 1.68) increased risk of graft loss and a 2.38-fold (95% confidence interval, 2.26 to 2.49) increased risk of mortality. We observed similar results for AD. We conclude that older KT recipients have a high risk of post-KT dementia and AD, and these sequelae associate with a profound effect on patient and graft survival.

OBJECTIVES/OBJECTIVE:Evidence suggests vitamin D deficiency is associated with developing frailty. However, cardiometabolic factors are related to both conditions and may confound and/or mediate the vitamin D-frailty association. We aimed to determine the association of vitamin D concentration with incidence of frailty, and the role of cardiometabolic diseases (cardiovascular disease, diabetes, hyperlipidemia, hypertension) in this relationship. DESIGN/METHODS:Prospective longitudinal cohort study (7 visits from 1994-2008). SETTING/METHODS:Baltimore, Maryland. PARTICIPANTS/METHODS:Three hundred sixty-nine women from the Women's Health and Aging Study II aged 70-79 years, free of frailty at baseline. MEASUREMENTS/METHODS:Serum circulating 25-hydroxyvitamin D (25[OH]D) concentration was assessed at baseline and categorized as: <10; 10-19.9; 20-29.9; and ≥30 ng/mL. Frailty incidence was determined based on presence of three or more criteria: weight loss, low physical activity, exhaustion, weakness, and slowness. Cardiometabolic diseases were ascertained at baseline. Analyses included Cox regression models adjusted for key covariates. RESULTS:Incidence rate of frailty was 32.2 per 1,000 person-years in participants with 25(OH)D < 10 ng/mL, compared to 12.9 per 1,000 person-years in those with 25(OH)D ≥ 30 ng/mL (mean follow-up = 8.5 ± 3.7 years). In cumulative incidence analyses, those with lower 25(OH)D exhibited higher frailty incidence, though differences were non-significant (P = .057). In regression models adjusted for demographics, smoking, and season, 25(OH)D < 10 ng/mL (vs ≥30 ng/mL) was associated with nearly three-times greater frailty incidence (hazard ratio (HR) = 2.77, 95% CI = 1.14, 6.71, P = .02). After adjusting for BMI, the relationship of 25(OH)D < 10 ng/mL (vs ≥30 ng/mL) with incident frailty persisted, but was attenuated after further accounting for cardiometabolic diseases (HR = 2.29, 95% CI = 0.92, 5.69, P = .07). CONCLUSION/CONCLUSIONS:Low serum vitamin D concentration is associated with incident frailty in older women; interestingly, the relationship is no longer significant after accounting for the presence of cardiometabolic diseases. Future studies should explore mechanisms to explain this relationship.

BACKGROUND:Frail individuals are at increased risk for poor outcomes, including adverse drug events. Kidney function is often compromised in frailty and is a key consideration in medication choice and dosing; however, creatinine-based measures of kidney function may be biased in frail individuals. STUDY DESIGN/METHODS:Observational study. SETTING & PARTICIPANTS/METHODS:4,987 community-dwelling older men and women with complete data who participated in visit 5 of the Atherosclerosis Risk in Communities (ARIC) Study (2011-2013). PREDICTORS/METHODS:) and urine albumin-creatinine ratio. OUTCOME/RESULTS:Frailty, defined using established criteria of 3 or more frailty characteristics (weight loss, slowness, exhaustion, weakness, and low physical activity). RESULTS:). Hyperpolypharmacy (taking ≥10 classes of medications) was more common in frail individuals (54% vs 38% of nonfrail), including classes requiring kidney clearance (eg, digoxin) and associated with falls and subsequent complications (eg, hypnotic/sedatives and anticoagulants). LIMITATIONS/CONCLUSIONS:Cross-sectional study design. CONCLUSIONS:. Given the substantial medication burden and uncertainty in chronic kidney disease classification, confirmation of kidney function with alternative biomarkers may be warranted to ensure careful prescribing practices in this vulnerable population.