Faculty Bibliography

BACKGROUND:It is unclear whether traditional and genetic risk factors in middle age predict the onset of gout in older age. METHODS:We studied the incidence of gout in older adults using the Atherosclerosis Risk in Communities study, a prospective U.S. population-based cohort of middle-aged adults enrolled between 1987 and 1989 with ongoing follow-up. A genetic urate score was formed from common urate-associated single nucleotide polymorphisms for eight genes. The adjusted hazard ratio and 95% confidence interval of incident gout by traditional and genetic risk factors in middle age were estimated using a Cox proportional hazards model. RESULTS:The cumulative incidence from middle age to age 65 was 8.6% in men and 2.5% in women; by age 75 the cumulative incidence was 11.8% and 5.0%. In middle age, increased adiposity, beer intake, protein intake, smoking status, hypertension, diuretic use, and kidney function (but not sex) were associated with an increased gout risk in older age. In addition, a 100 µmol/L increase in genetic urate score was associated with a 3.29-fold (95% confidence interval: 1.63-6.63) increased gout risk in older age. CONCLUSIONS:These findings suggest that traditional and genetic risk factors in middle age may be useful for identifying those at risk of gout in older age.

Married couples might be an appropriate target for obesity prevention interventions. In the present study, we aimed to evaluate whether an individual's risk of obesity is associated with spousal risk of obesity and whether an individual's change in body mass index (BMI; weight in kilograms divided by height in meters squared) is associated with spousal BMI change. We analyzed data from 3,889 spouse pairs in the Atherosclerosis Risk in Communities Study cohort who were sampled at ages 45-65 years from 1986 to 1989 and followed for up to 25 years. We estimated hazard ratios for incident obesity by whether spouses remained nonobese, became obese, remained obese, or became nonobese. We estimated the association of participants' BMI changes with concurrent spousal BMI changes using linear mixed models. Analyses were stratified by sex. At baseline, 22.6% of men and 24.7% of women were obese. Nonobese participants whose spouses became obese were more likely to become obese themselves (for men, hazard ratio = 1.78, 95% confidence interval: 1.30, 2.43; for women, hazard ratio = 1.89, 95% confidence interval: 1.39, 2.57). With each 1-unit increase in spousal BMI change, women's BMI change increased by 0.15 (95% confidence interval: 0.13, 0.18) and men's BMI change increased by 0.10 (95% confidence interval: 0.09, 0.12). Having a spouse become obese nearly doubles one's risk of becoming obese. Future research should consider exploring the efficacy of obesity prevention interventions in couples.

BACKGROUND:Dual-energy computed tomography (DECT) is a new diagnostic tool for gout, but its sensitivity has not been established. Our goal was to assess the sensitivity of DECT for the detection of monosodium urate (MSU) deposits in non-tophaceous and tophaceous gout, both at the level of the patient and that of the individual joint or lesion. METHODS:DECT was performed on 11 patients with crystal-proven non-tophaceous gout and 10 with tophaceous gout and included both the upper and lower extremities in 20/21 patients. DECT images were simultaneously acquired at 80 and 140 kV and then processed on a workstation with proprietary software using a two-material decomposition algorithm. MSU deposits were color coded as green by the software and fused onto grey-scale CT images. The number and location of these deposits was tallied independently by two DECT-trained radiologists blinded to the clinical characteristics of the patient. Sensitivity of DECT was defined as the proportion of patients with a confirmed diagnosis of gout which was correctly identified as such by the imaging technique. All patients provided informed consent to participate in this IRB-approved study. RESULTS:MSU deposits were detected by DECT in ≥1 joint area in 7/11 (64 %) patients with non-tophaceous gout, but were only detected in 3/12 (25 %) joints proven by aspiration to be affected with gout. Inclusion of the upper extremity joints in the scanning protocol did not improve sensitivity. All 10 patients with tophaceous gout had MSU deposits evident by DECT. The sensitivity of DECT for individual gouty erosions was assessed in 3 patients with extensive foot involvement. MSU deposits were detected by DECT within or immediately adjacent to 13/26 (50 %) erosions. CONCLUSIONS:A DECT protocol that includes all lower extremity joints has moderate sensitivity in non-tophaceous and high sensitivity in tophaceous gout. However, DECT has lower sensitivity when restricted to individual crystal-proven gouty joints in non-tophaceous disease or individual erosive lesions in tophaceous gout. The detection of MSU deposits by DECT relates to their size and density and the detection parameters of the DECT scanner and adjustment of the latter might improve sensitivity.

BACKGROUND:People with end-stage renal disease are at high risk for bone fracture. Less is known about fracture risk in milder chronic kidney disease and whether chronic kidney disease-associated fracture risk varies by sex or assessment with alternative kidney markers. STUDY DESIGN/METHODS:Prospective cohort study. SETTING & PARTICIPANTS/METHODS:10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. PREDICTOR/METHODS:Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFRcr), urine albumin-creatinine ratio, and alternative filtration markers. OUTCOMES/RESULTS:Fracture-related hospitalizations determined by diagnostic code. MEASUREMENTS/METHODS:Baseline kidney markers; hospitalizations identified by self-report during annual telephone contact and active surveillance of local hospital discharge lists. RESULTS:Mean age of participants was 63 years, 56% were women, and 22% were black. During a median follow-up of 13 years, there were 722 incident fracture-related hospitalizations. Older age, female sex, and white race were associated with higher risk for fracture (P<0.001). The relationship between eGFRcr and fracture risk was nonlinear: <60mL/min/1.73m(2), lower eGFRcr was associated with higher fracture risk (adjusted HR per 10mL/min/1.73m(2) lower, 1.24; 95% CI, 1.05-1.47); there was no statistically significant association for ≥60mL/min/1.73m(2) in the primary analysis. In contrast, there was a graded association between other markers of kidney function and subsequent fracture, including albumin-creatinine ratio (HR per doubling, 1.10; 95% CI, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% CI, 1.06-1.25), and 1/β2-microglobulin (HR per 1-SD decrease, 1.26, 95% CI, 1.15-1.37). LIMITATIONS/CONCLUSIONS:No bone mineral density assessment; one-time measurement of kidney function. CONCLUSIONS:Both low eGFR and higher albuminuria were significant risk factors for fracture in this community-based population. The shape of the association in the upper ranges of eGFR varied by the filtration marker used in estimation.

Early hospital readmission is associated with increased morbidity, mortality, and cost. Following simultaneous pancreas-kidney transplantation, rates of readmission and risk factors for readmission are unknown. We used United States Renal Data System data to study 3643 adult primary first-time simultaneous pancreas-kidney recipients from December 1, 1999 to October 31, 2011. Early hospital readmission was any hospitalization within 30 days of discharge. Modified Poisson regression was used to determine the association between readmission and patient-level factors. Empirical Bayes statistics were used to determine the variation attributable to center-level factors. The incidence of readmission was 55.5%. Each decade increase in age was associated with an 11% lower risk of readmission to age 40, beyond which there was no association. Donor African-American race was associated with a 13% higher risk of readmission. Each day increase in length of stay was associated with a 2% higher risk of readmission until 14 days, beyond which each day increase was associated with a 1% reduction in the risk of readmission. Center-level factors were not associated with readmission. The high incidence of early hospital readmission following simultaneous pancreas-kidney transplant may reflect clinical complexity rather than poor quality of care.

BACKGROUND: Frailty is associated with worse health-related quality of life (HRQOL) in older adults and worse clinical outcomes in adults of all ages with end stage renal disease (ESRD). It is unclear whether frail adults of all ages with ESRD are more likely to experience worse HRQOL. OBJECTIVE: The goal of this study was to identify factors associated with worsening HRQOL in this population. DESIGN, SETTING AND MEASUREMENTS: We studied 233 adults of all ages with ESRD enrolled (11/2009-11/2013) in a longitudinal cohort study. Frailty status was measured at enrollment and HRQOL was reported (Excellent, Very Good, Good, Fair or Poor) at the initial assessment and follow-up (median follow-up 9.4 months). We studied factors associated with Fair/Poor HRQOL at follow-up using logistic regression and factors associated with HRQOL change using multinomial regression. All models were adjusted for age, sex, race, education, BMI, diabetes status, history of a previous transplant, type of dialysis and time between assessments. RESULTS: Fair/Poor HRQOL was reported by 28% at initial assessment and 33% at follow-up. 47.2% of participants had stable HRQOL, 22.8% better HRQOL, and 30.0% worse HRQOL at follow-up (P<0.001). In adjusted models, only frailty was associated with Fair/Poor HRQOL at follow-up (OR: 2.79, 95% CI: 1.32-5.90) and worsening HRQOL at follow-up (RR: 2.91, 95%CI: 1.08-7.80). CONCLUSIONS: Frail adults of all ages with ESRD are more likely to experience fair/poor HRQOL and worsening HRQOL over time. Frailty represents a state of decreased physiologic reserve that impacts not only clinical outcomes but also the patient-centered outcome of HRQOL.