Objectives To quantify the prevalence of frailty in adult patients of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization. Design Prospective cohort study. Setting Single hemodialysis center in Baltimore, Maryland. Participants 146 prevalent hemodialysis patients enrolled between January 2009 and March 2010 and followed through August 2012. Measurements Frailty, comorbidity, and disability on enrollment into the study and subsequent mortality and hospitalizations. Results At enrollment, 50.0% of older (age≥65) and 35.4% of younger (age<65) hemodialysis patients were frail; 35.9% and 29.3% were intermediately frail, respectively. The 3-year mortality was 16.2% for non frail, 34.4% for intermediately frail, and 40.2% for frail participants. Intermediate frailty and frailty were associated with a 2.68-fold (95% CI: 1.02-7.07, P=0.046) and 2.60-fold (95%CI: 1.04-6.49, P=0.041) higher risk of death independent of age, sex, comorbidity, and disability. In the year after enrollment, median number of hospitalizations was 1 (IQR 0-3). The proportion with 2 or more hospitalizations was 28.2% for non frail, 25.5% for intermediately frail, and 42.6% for frail participants. While intermediate frailty was not associated with the number of hospitalizations (RR=0.76, 95%CI:0.49-1.16, P=0.21), frailty was associated with a 1.43-fold (95%CI:1.00-2.03, P=0.049) higher number of hospitalizations independent of age, sex, comorbidity, and disability. The association of frailty with mortality and hospitalizations did not differ between older and younger participants (Interaction P=0.64 and P=0.14, respectively). Conclusions Adults of all ages undergoing hemodialysis have a very high prevalence of frailty, more than 5-fold higher than community dwelling older adults. In this population, regardless of age, frailtyis a strong, independent predictor of mortality and number of hospitalizations.

We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01–4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.

Early hospital readmission (EHR) after kidney transplantation (KT) is associated with increased morbidity and higher costs. Registry-based recipient, transplant, and center-level predictors of EHR are limited, and novel predictors are needed. We hypothesized that frailty, a measure of physiologic reserve initially described and validated in geriatrics and recently associated with early KT outcomes, might serve as a novel, independent predictor of EHR in KT recipients of all ages. We measured frailty in 383 KT recipients at Johns Hopkins Hospital. EHR was ascertained from medical records as ≥1 hospitalization within 30 days of initial post-KT discharge. Frail KT recipients were much more likely to experience EHR (45.8% vs. 28.0%, P=0.005), regardless of age. After adjusting for previously described registry-based risk factors, frailty independently predicted 61% higher risk of EHR (adjusted RR=1.61, 95% CI: 1.18–2.19, P=0.002). In addition, frailty improved EHR risk prediction by improving the area under the receiver operating characteristic curve (P=0.01) as well as the net reclassification index (P=0.04). Identifying frail KT recipients for targeted outpatient monitoring and intervention may reduce EHR rates.

Early hospital readmission (EHR) is associated with increased morbidity, costs and transition-of-care errors. We sought to quantify rates of and risk factors for EHR after kidney transplantation (KT). We studied 32 961 Medicare primary KT recipients (2000)(2001)(2002)(2003)(2004)(2005) linked to Medicare claims through the United States Renal Data System. EHR was defined as at least one hospitalization within 30 days of initial discharge after KT. The association between EHR and recipient and transplant factors was explored using Poisson regression; hierarchical modeling was used to account for study center-level differences. The overall EHR rate was 31%, and 19 independent patient-level factors associated with EHR were identified: recipient factors included older age, African American race and various comorbidities; transplant factors included ECD, length of stay and lack of induction therapy. The unadjusted rate of EHR by center ranged from 18% to 47%, but conventional center-level factors (percent African American, percent age > 60, percent deceased donor and percent expanded criteria donor) were not associated with EHR. However, intermediate total volume and average length of stay were associated with increased EHR risk. Better identification of patients at risk for early hospital readmission following KT may guide discharge planning and early posttransplant outpatient monitoring. Key words: Hospital readmission, kidney transplantAbbreviations: BMI, body mass index; CHF, congestive heart failure; CI, confidence interval; CMS, centers for medicare and medicaid services; COPD, chronic obstructive pulmonary disease; ECD, extended criteria donor; EHR, early hospital readmission; HCV, hepatitis C virus; HLA, human leukocyte antigen; HTN, hypertension; IQR, inter-quartile range; KT, kidney transplant; MI, myocardial infarction; OPTN, organ procurement and transplant network; RR, relative risk; SD, standard deviation; USRDS, United States Renal Data System.

chronic kidney disease; CST, Canadian Society of Transplantation; CT, computed tomography; DASI, Duke activity status index; DEXA, dual energy X-ray absorptiometry; ESRD, end-stage renal disease; FFP, fried frailty phenotype; HR, hazard ratio; HRQO, health-related quality of life; MCSD, mechanical circulatory support device; MELDNa, model for end-stage liver disease and sodium; MRI, magnetic resonance imaging; SPPB, short physical performance battery.

Background & Aims: Frailty is associated with mortality in patients with cirrhosis. We measured frailty using 3 simple tests and calculated liver frailty index (LFI) scores for patients at multiple ambulatory centers. We investigated associations between LFI scores, ascites, and hepatic encephalopathy (HE) and mortality. Methods: Adults without hepatocellular carcinoma who were on the liver transplant waitlist at 9 centers in the United States (n=1044) were evaluated using the LFI; LFI scores of 4.5 or more indicated that patients were frail. We performed logistic regression analyses to assess associations between frailty and ascites or HE and competing risk regression analyses (with liver transplantation as the competing risk) to estimate subhazard ratios (sHR) of waitlist mortality (death or removal from the waitlist). Results: Of study subjects, 36% had ascites, 41% had HE, and 25% were frail. The odds of frailty were higher for patients with ascites (adjusted odd ratio, 1.56; 95% CI, 1.15-2.14) or HE (OR, 2.45; 95% CI, 1.80-3.33) than without these features. Higher proportions of frail patients with ascites (29%) or HE (30%) died while on the waitlist compared to patients who were not frail (17% of patients with ascites and 20% with HE). In univariable analysis, ascites (sHR, 1.52; 95% CI, 1.14-2.05), HE (sHR, 1.84; 95% CI, 1.38-2.45), and frailty (sHR, 2.38; 95% CI, 1.77-3.20) were associated with waitlist mortality. In adjusted models, only frailty remained significantly associated with waitlist mortality (sHR, 1.82; 95% CI, 1.31-2.52)-ascites and HE were not. Conclusions: Frailty is a prevalent complication of cirrhosis that is observed more frequently in patients with ascites or HE and independently associated with waitlist mortality. LFI scores can be Lai et al.

BackgroundPatients undergoing hemodialysis are at high risk of falls, with subsequent complications including fractures, loss of independence, hospitalization, and institutionalization. Factors associated with falls are poorly understood in this population. We hypothesized that insights derived from studies of the elderly might apply to adults of all ages undergoing hemodialysis; we focused on frailty, a phenotype of physiological decline strongly associated with falls in the elderly.MethodsIn this prospective, longitudinal study of 95 patients undergoing hemodialysis (1/2009-3/2010), the association of frailty with future falls was explored using adjusted Poisson regression. Frailty was classified using the criteria established by Fried et al., as a combination of five components: shrinking, weakness, exhaustion, low activity, and slowed walking speed.ResultsOver a median 6.7-month period of longitudinal follow-up, 28.3% of study participants (25.9% of those under 65, 29.3% of those 65 and older) experienced a fall. After adjusting for age, sex, race, comorbidity, disability, number of medications, marital status, and education, frailty independently predicted a 3.09-fold (95% CI: 1.38-6.90, P=0.006) higher number of falls. This relationship between frailty and falls did not differ for younger and older adults (P=0.57).ConclusionsFrailty, a validated construct in the elderly, was a strong and independent predictor of falls in adults undergoing hemodialysis, regardless of age. Our results may aid in identifying frail hemodialysis patients who could be targeted for multidimensional fall prevention strategies.

Background and objectives Patients of all ages undergoing hemodialysis (HD) have a high prevalence of cognitive impairment and worse cognitive function than healthy controls, and those with dementia are at high risk of death. Frailty has been associated with poor cognitive function in older adults without kidney disease. We hypothesized that frailty might also be associated with poor cognitive function in adults of all ages undergoing HD.Design, setting, participants, & measurements At HD initiation, 324 adults enrolled (November 2008 to July 2012) in a longitudinal cohort study (Predictors of Arrhythmic and Cardiovascular Risk in ESRD) were classified into three groups (frail, intermediately frail, and nonfrail) based on the Fried frailty phenotype. Global cognitive function (3MS) and speed/attention (Trail Making Tests A and B [TMTA and TMTB, respectively]) were assessed at cohort entry and 1-year follow-up. Associations between frailty and cognitive function (at cohort entry and 1-year follow-up) were evaluated in adjusted (for sex, age, race, body mass index, education, depression and comorbidity at baseline) linear (3MS, TMTA) and Tobit (TMTB) regression models.Results At cohort entry, the mean age was 54.8 years (SD 13.3), 56.5% were men, and 72.8% were black. The prevalence of frailty and intermediate frailty were 34.0% and 37.7%, respectively. The mean 3MS was 89.8 (SD 7.6), TMTA was 55.4 (SD 29), and TMTB was 161 (SD 83). Frailty was independently associated with lower cognitive function at cohort entry for all three measures (3MS: 22.4 points; 95% confidence interval [95% CI], 24.2 to 20.5; P=0.01; TMTA: 12.1 seconds; 95% CI, 4.7 to 19.4; P,0.001; and TMTB: 33.2 seconds; 95% CI, 9.9 to 56.4; P=0.01; all tests for trend, P,0.001) and with worse 3MS at 1-year follow-up (22.8 points; 95% CI, 25.4 to 20.2; P=0.03). ConclusionsIn adult incident HD patients, frailty is associated with worse cognitive function, particularly global cognitive function (3MS).