Faculty Bibliography

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.

BACKGROUND:Reduced kidney function is a risk factor for hyperuricaemia and gout, but limited information on the burden of gout is available from studies of patients with chronic kidney disease (CKD). We therefore examined the prevalence and correlates of gout in the large prospective observational German Chronic Kidney Disease (GCKD) study. METHODS:Data from 5085 CKD patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) of 30-<60 mL/min/1.73 m(2) or eGFR ≥60 and overt proteinuria at recruitment and non-missing values for self-reported gout, medications and urate measurements from a central laboratory were evaluated. RESULTS:The overall prevalence of gout was 24.3%, and increased from 16.0% in those with eGFR ≥60 mL/min/1.73 m(2) to 35.6% in those with eGFR <30. Of those with self-reported gout, 30.7% of individuals were not currently taking any gout medication and among gout patients on urate lowering therapy, 47.2% still showed hyperuricaemia. Factors associated with gout were serum urate, lower eGFR, advanced age, male sex, higher body mass index and waist-to-hip ratio, higher triglyceride and C-reactive protein (CRP) concentrations, alcohol intake and diuretics use. While lower eGFR categories showed significant associations with gout in multivariable-adjusted models (prevalence ratio 1.46 for eGFR <30 compared with eGFR ≥60, 95% confidence interval 1.21-1.77), associations between gout and higher urinary albumin-to-creatinine ratio in this CKD population were not significant. CONCLUSIONS:Self-reported gout is common among patients with CKD and lower GFR is strongly associated with gout. Pharmacological management of gout in patients with CKD is suboptimal. Prospective follow-up will show whether gout and hyperuricaemia increase the risk of CKD progression and cardiovascular events in the GCKD study.

OBJECTIVE:To determine whether the Sjögren's syndrome B (SSB)-positive/Sjögren's syndrome A (SSA)-negative antibody profile is associated with key phenotypic features of SS. METHODS:Among registrants in the Sjögren's International Collaborative Clinical Alliance (SICCA) with possible or established SS, we compared anti-SSA/anti-SSB reactivity profiles against concurrent phenotypic features. We fitted logistic regression models to explore the association between anti-SSA/anti-SSB reactivity profile and each key SS phenotypic feature, controlling for potential confounders. RESULTS:Among 3297 participants, 2061 (63%) had negative anti-SSA/anti-SSB, 1162 (35%) had anti-SSA with or without anti-SSB, and 74 (2%) anti-SSB alone. Key SS phenotypic features were more prevalent and had measures indicative of greater disease activity in those participants with anti-SSA, either alone or with anti-SSB, than in those with anti-SSB alone or negative SSA/SSB serology. These between-group differences were highly significant and not explained by confounding by age, race/ethnicity or gender. Participants with anti-SSB alone were comparable to those with negative SSA/SSB serology in their association with these key phenotypic features. Among SICCA participants classified with SS on the basis of the American-European Consensus Group or American College of Rheumatology criteria, only 2% required the anti-SSB-alone test result to meet these criteria. CONCLUSIONS:The presence of anti-SSB, without anti-SSA antibodies, had no significant association with SS phenotypic features, relative to seronegative participants. The solitary presence of anti-SSB antibodies does not provide any more support than negative serology for the diagnosis of SS. This serological profile should thus be interpreted cautiously in clinical practice and potentially eliminated from future classification criteria.

BACKGROUND:Frailty, a validated measure of physiologic reserve, predicts adverse health outcomes among adults with end-stage renal disease. Frailty typically is not measured clinically; instead, a surrogate-perceived frailty-is used to inform clinical decision-making. Because correlations between perceived and measured frailty remain unknown, the aim of this study was to assess their relationship. METHODS:146 adults undergoing hemodialysis were recruited from a single dialysis center in Baltimore, Maryland. Patient characteristics associated with perceived (reported by nephrologists, nurse practitioners (NPs), or patients) or measured frailty (using the Fried criteria) were identified using ordered logistic regression. The relationship between perceived and measured frailty was assessed using percent agreement, kappa statistic, Pearson's correlation coefficient, and prevalence of misclassification of frailty. Patient characteristics associated with misclassification were determined using Fisher's exact tests, t-tests, or median tests. RESULTS:Older age (adjusted OR [aOR] = 1.36, 95%CI:1.11-1.68, P = 0.003 per 5-years older) and comorbidity (aOR = 1.49, 95%CI:1.27-1.75, P < 0.001 per additional comorbidity) were associated with greater likelihood of nephrologist-perceived frailty. Being non-African American was associated with greater likelihood of NP- (aOR = 5.51, 95%CI:3.21-9.48, P = 0.003) and patient- (aOR = 4.20, 95%CI:1.61-10.9, P = 0.003) perceived frailty. Percent agreement between perceived and measured frailty was poor (nephrologist, NP, and patient: 64.1%, 67.0%, and 55.5%). Among non-frail participants, 34.4%, 30.0%, and 31.6% were perceived as frail by a nephrologist, NP, or themselves. Older adults (P < 0.001) were more likely to be misclassified as frail by a nephrologist; women (P = 0.04) and non-African Americans (P = 0.02) were more likely to be misclassified by an NP. Neither age, sex, nor race was associated with patient misclassification. CONCLUSIONS:Perceived frailty is an inadequate proxy for measured frailty among patients undergoing hemodialysis.

OBJECTIVE:Gout prevalence is high in older adults and those affected are at risk of physical disability, yet it is unclear whether they have worse physical function. METHODS:We studied gout, hyperuricemia, and physical function in 5,819 older adults (age ≥65 years) attending the 2011-2013 Atherosclerosis Risk in Communities Study visit, a prospective US population-based cohort. Differences in lower extremity function (Short Physical Performance Battery [SPPB] and 4-meter walking speed) and upper extremity function (grip strength) by gout status and by hyperuricemia prevalence were estimated in adjusted ordinal logistic regression (SPPB) and linear regression (walking speed and grip strength) models. Lower scores or times signify worse function. The prevalence of poor physical performance (first quartile) by gout and hyperuricemia was estimated using adjusted modified Poisson regression. RESULTS:Ten percent of participants reported a history of gout and 21% had hyperuricemia. There was no difference in grip strength by history of gout (P = 0.77). Participants with gout performed worse on the SPPB test; they had 0.77 times (95% confidence interval [95% CI] 0.65, 0.90, P = 0.001) the prevalence odds of a 1-unit increase in SPPB score and were 1.18 times (95% CI 1.07, 1.32, P = 0.002) more likely to have poor SPPB performance. Participants with a history of gout had slower walking speed (mean difference -0.03; 95% CI -0.05, -0.01, P < 0.001) and were 1.19 times (95% CI 1.06, 1.34, P = 0.003) more likely to have poor walking speed. Similarly, SPPB score and walking speed, but not grip strength, were worse in participants with hyperuricemia. CONCLUSION/CONCLUSIONS:Older adults with gout and hyperuricemia are more likely to have worse lower extremity, but not upper extremity, function.

OBJECTIVES/OBJECTIVE:To understand the natural history of frailty after an aggressive surgical intervention, kidney transplantation (KT). DESIGN/METHODS:Prospective cohort study (December 2008-March 2014). SETTING/METHODS:Baltimore, Maryland. PARTICIPANTS/METHODS:Kidney transplantation recipients (N = 349). MEASUREMENTS/METHODS:The Fried frailty score was measured at the time of KT and during routine clinical follow-up. Using a Cox proportional hazards model, factors associated with improvements in frailty score after KT were identified. Using a longitudinal analysis, predictors of frailty score changes after KT were identified using a multilevel mixed-effects Poisson model. RESULTS:At KT, 19.8% of recipients were frail; 1 month after KT, 33.3% were frail; at 2 months, 27.7% were frail; and at 3 months, 17.2% were frail. On average, frailty scores had worsened by 1 month (mean change 0.4, P < .001), returned to baseline by 2 months (mean change 0.2, P = .07), and improved by 3 months (mean change -0.3, P = .04) after KT. The only recipient or transplant factor associated with improvement in frailty score after KT was pre-KT frailty (hazard ratio = 2.55, 95% confidence interval (CI) = 1.71-3.82, P < .001). Pre-KT frailty status (relative risk (RR) = 1.49, 95% CI = 1.29-1.72, P < .001), recipient diabetes mellitus (RR = 1.26, 95% CI = 1.08-1.46, P = .003), and delayed graft function (RR = 1.22, 95% CI = 1.04-1.43, P = .02) were independently associated with long-term changes in frailty score. CONCLUSION/CONCLUSIONS:After KT, in adult recipients of all ages, frailty initially worsens but then improves by 3 months. Although KT recipients who were frail at KT had higher frailty scores over the long term, they were most likely to show improvements in their physiological reserve after KT, supporting the transplantation in these individuals and suggesting that pretransplant frailty is not an irreversible state of low physiological reserve.

BACKGROUND AND OBJECTIVES/OBJECTIVE: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/METHODS: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).