Faculty Bibliography

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.

OBJECTIVE:The effects of carbohydrates on plasma uric acid levels are a subject of controversy. We determined the individual and combined effects of carbohydrate quality (the glycemic index) and quantity (the proportion of total daily energy [percentage of carbohydrates]) on uric acid levels. METHODS:We conducted a randomized, crossover trial of 4 different diets in overweight or obese adults without cardiovascular disease (n = 163). Participants consumed each of 4 diets over a 5-week period, each of which was separated by a 2-week washout period. Body weight was kept constant. The 4 diets were high glycemic index (≥65) with high percentage of carbohydrates (58% kcal), low glycemic index (≤45) with low percentage of carbohydrates (40% kcal), low glycemic index with high percentage of carbohydrates, and high glycemic index with low percentage of carbohydrates. Plasma uric acid levels were measured at baseline and after completion of each 5-week period for comparison between the 4 diets. RESULTS:Of the 163 study participants, 52% were women and 50% were non-Hispanic African American subjects; their mean age was 52.6 years, and their mean ± SD uric acid level was 4.7 ± 1.2 mg/dl. Reducing the glycemic index lowered uric acid levels when the percentage of carbohydrates was low (-0.24 mg/dl; P < 0.001) or high (-0.17 mg/dl; P < 0.001). Reducing the percentage of carbohydrates marginally increased the uric acid level only when the glycemic index was high (P = 0.05). The combined effect of lowering the glycemic index and increasing the percentage of carbohydrates was -0.27 mg/dl (P < 0.001). This effect was observed even after adjustment for concurrent changes in kidney function, insulin sensitivity, and products of glycolysis. CONCLUSION:Reducing the glycemic index lowers uric acid levels. Future studies should examine whether reducing the glycemic index can prevent gout onset or flares.

OBJECTIVE:Anticentromere antibodies (ACAs) define a subset of primary Sjögren's syndrome (SS) with a unique phenotype, including features of limited cutaneous systemic sclerosis and a lower frequency of anti-SSA/SSB antibodies. We sought to determine whether ACAs are associated with more severe exocrine glandular dysfunction in a large cohort of primary SS subjects. METHODS:We performed a cross-sectional analysis of 1,361 subjects with primary SS from the Sjögren's International Collaborative Clinical Alliance Registry, stratified by the presence or absence of ACAs. ACAs were assayed by immunofluorescence staining on HEp-2 cells. RESULTS:ACAs were present in 82 of the 1,361 SS subjects (6%) and were associated with older age, female sex, and lower frequencies of anti-SSA/SSB, rheumatoid factor, and hyperglobulinemia. Among ACA-positive versus ACA-negative subjects, there was a higher frequency of a focus score ≥2 (71% versus 53%; P = 0.002), a higher median focus score (2.8 versus 2.5; P = 0.0440), and greater exocrine gland dysfunction: Schirmer's test value: median 4 versus 5 mm/5 minutes; P = 0.0003, and unstimulated whole saliva (UWS) flow rate: median 0.08 versus 0.37 ml/5 minutes; P < 0.0001. ACA-positive subjects had an increased risk of UWS <0.1 ml/minute (odds ratio [OR] 12.24 [95% confidence interval (95% CI) 4.91-41.02]) and Schirmer's test value <5 mm/5 minutes (OR 2.52 [95% CI 1.50-4.36]) after correcting for age, sex, anti-SSA/SSB, and focus score. Labial gland fibrosis was not different between the 2 groups. CONCLUSION:In a large international registry of SS, ACA had an independent association with more severe exocrine glandular dysfunction. This dysfunction was associated with more pronounced labial salivary glandular inflammation but not fibrosis.

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.

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.

OBJECTIVES/OBJECTIVE:To investigate the association between serum potassium, mortality, and kidney outcomes in the general population and whether potassium-altering medications modify these associations. PATIENTS AND METHODS/METHODS:We studied 15,539 adults in the Atherosclerosis Risk in Communities Study. Cox proportional hazard regression was used to investigate the association of serum potassium at baseline (1987-1989), evaluated categorically (hypokalemia, <3.5 mmol/L; normokalemia, ≥3.5 and <5.5 mmol/L; hyperkalemia, ≥5.5 mmol/L) and continuously using linear spline terms (knots at 3.5 and 5.5 mmol/L), with mortality, sudden cardiac death, incident chronic kidney disease, and end-stage renal disease. The end date of follow-up for all outcomes was December 31, 2012. We also evaluated whether classes of potassium-altering medications modified the association between serum potassium and adverse outcomes. RESULTS:Overall, 413 (2.7%) of the participants had hypokalemia and 321 (2.1%) had hyperkalemia. In a fully adjusted model, hyperkalemia was significantly associated with mortality (hazard ratio, 1.24; 95% CI, 1.04-1.49) but not sudden cardiac death, chronic kidney disease, or end-stage renal disease. Hypokalemia as a categorical variable was not associated with any outcome; however, associations of hypokalemia with all-cause mortality and kidney outcomes were observed among those who were not taking potassium-wasting diuretics (all P for interaction, <.001). CONCLUSIONS:Higher values of serum potassium were associated with a higher risk of mortality in the general population. Lower levels of potassium were associated with adverse kidney outcomes and mortality among participants not taking potassium-wasting diuretics.

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.

There is an increased risk of acute rejection (AR) in human immunodeficiency virus-positive (HIV+) kidney transplant (KT) recipients. Induction immunosuppression is standard of care for those at high risk of AR; however, use in HIV+ patients is controversial, given fears of increased infection rates. We sought to compare clinical outcomes between HIV+ KT recipients who were treated with (i) anti-thymocyte globulin (ATG), (ii) IL-2 receptor blocker, and (iii) no induction. We studied 830 HIV+ KT recipients between 2000 and 2014, as captured in the Scientific Registry of Transplant Recipients, and compared rates of delayed graft function (DGF), AR, graft loss and death. Infections and hospitalizations were ascertained by International Classification of Diseases, Ninth Revision codes in a subset of 308 patients with Medicare. Compared with no induction, neither induction agent was associated with an increased risk of infection (weighted hazard ratio [wHR] 0.80, 95% confidence interval [CI] 0.55-1.18). HIV+ recipients who received induction spent fewer days in the hospital (weighted relative risk [wRR] 0.70, 95% CI 0.52-0.95), had lower rates of DGF (wRR 0.66, 95% CI 0.51-0.84), less graft loss (wHR 0.47, 95% CI 0.24-0.89) and a trend toward lower mortality (wHR 0.60, 95% CI 0.24-1.28). Those who received induction with ATG had lower rates of AR (wRR 0.59, 95% CI 0.35-0.99). Induction in HIV+ KT recipients was not associated with increased infections; in fact, those receiving ATG, the most potent agent, had the lowest rates. In light of the high risk of AR in this population, induction therapy should be strongly considered.