Mara A. McAdams-DeMarco

Frailty as a Novel Predictor of Mortality and Hospitalization in Individuals of All Ages Undergoing Hemodialysis

To quantify the prevalence of frailty in adults of all ages undergoing chronic hemodialysis, its relationship to comorbidity and disability, and its association with adverse outcomes of mortality and hospitalization.

Frailty and Early Hospital Readmission After Kidney Transplantation

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.

Frailty and Mortality in Kidney Transplant Recipients

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 After Kidney Transplantation: Patient and Center‐Level Associations

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 (2000–2005) 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.

Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study

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.

Frailty and Cognitive Function in Incident Hemodialysis Patients

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: -2.4 points; 95% confidence interval [95% CI], -4.2 to -0.5; 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 (-2.8 points; 95% CI, -5.4 to -0.2; P=0.03). CONCLUSIONS In adult incident HD patients, frailty is associated with worse cognitive function, particularly global cognitive function (3MS).

A urate gene-by-diuretic interaction and gout risk in participants with hypertension: results from the ARIC study

Objective To test for a urate gene-by-diuretic interaction on incident gout. Methods The Atherosclerosis Risk in Communities Study is a prospective population-based cohort of 15 792 participants recruited from four US communities (1987–1989). Participants with hypertension and available single nucleotide polymorphism (SNP) genotype data were included. A genetic urate score (GUS) was created from common urate-associated SNPs for eight genes. Gout incidence was self-reported. Using logistic regression, the authors estimated the adjusted OR of incident gout by diuretic use, stratified by GUS median. Results Of 3524 participants with hypertension, 33% used a diuretic and 3.1% developed gout. The highest 9-year cumulative incidence of gout was in those with GUS above the median and taking a thiazide or loop diuretic (6.3%). Compared with no thiazide or loop diuretic use, their use was associated with an OR of 0.40 (95% CI 0.14 to 1.15) among those with a GUS below the median and 2.13 (95% CI 1.23 to 3.67) for those with GUS above the median; interaction p=0.006. When investigating the genes separately, SLC22A11 and SLC2A9 showed a significant interaction, consistent with the former encoding an organic anion/dicarboxylate exchanger, which mediates diuretic transport in the kidney. Conclusions Participants who were genetically predisposed to hyperuricaemia were susceptible to developing gout when taking thiazide or loop diuretics, an effect not evident among those without a genetic predisposition. These findings argue for a potential benefit of genotyping individuals with hypertension to assess gout risk, relative in part to diuretic use.

Trends in kidney transplant outcomes in older adults.

To estimate mortality and death‐censored graft loss according to year of kidney transplant (KT) between 1990 and 2011.

Hypertension and the Risk of Incident Gout in a Population‐Based Study: The Atherosclerosis Risk in Communities Cohort

J Clin Hypertens (Greenwich). 2012; 14:675–679. ©2012 Wiley Periodicals, Inc.

Age and Sex Disparities in Discussions About Kidney Transplantation in Adults Undergoing Dialysis

To explore whether disparities in age and sex in access to kidney transplantation (KT) originate at the time of prereferral discussions about KT.