Kidney Function and Fracture Risk: The Atherosclerosis Risk in Communities (ARIC) Study

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: Prospective cohort study. Setting & Participants: 10,955 participants from the Atherosclerosis Risk in Communities (ARIC) Study followed up from 1996 to 2011. Predictor: Kidney function as assessed by creatinine-based estimated glomerular filtration rate (eGFR(cr)), urine albumin-creatinine ratio, and alternative filtration markers. Outcomes: Fracture-related hospitalizations determined by diagnostic code. Measurements: 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 eGFR(cr) and fracture risk was nonlinear: <60 mL/min/1.73 m(2), lower eGFR(cr) was associated with higher fracture risk (adjusted HR per 10 mL/min/1.73 m(2) lower, 1.24; 95% Cl, 1.05-1.47); there was no statistically significant association for >= 60 mL/min/1.73 m(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% Cl, 1.06-1.14), cystatin C-based eGFR (HR per 1-SD decrease, 1.15; 95% Cl, 1.06-1.25), and 1/beta(2)-microglobulin (HR per 1-SD decrease, 1.26, 95% Cl, 1.15-1.37). Limitations: 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. (C) 2016 by the National Kidney Foundation, Inc.