Abstract
RATIONALE: Adults with cystic fibrosis (CF) possess multiple potential risk factors for chronic kidney disease, including CF-related diabetes (CFRD) and lifetime nephrotoxic drug exposure. OBJECTIVES: To determine whether cumulative intravenous (IV) aminoglycoside exposure and CFRD increase the risk of chronic kidney disease in adults with CF. METHODS: This was a cohort study using adults (≥ 18 yr) in the CF Foundation registry from 2001-2008. Chronic kidney disease (stage 3 or greater) was defined by an estimated glomerular filtration rate of less than 60 ml/min/1.73 m(2). Time-dependent multivariable Cox proportional hazards models were used to determine whether cumulative number of acute pulmonary exacerbations (surrogate for IV aminoglycoside exposure) and CFRD requiring insulin increase the risk of chronic kidney disease, adjusting for confounders. MEASUREMENTS AND MAIN RESULTS: The study cohort included 11,912 adults with a median follow-up of 4 years. During the study period, 204 subjects had chronic kidney disease, with an annual disease prevalence of 2.3%. Disease prevalence doubled with every 10-year increase in age. CFRD requiring insulin therapy substantially increased the risk of chronic kidney disease (1-4 yr of CFRD requiring insulin vs. no CFRD, hazard ratio [HR] = 2.40, 95% confidence interval [CI] 1.74-3.32; ≥ 5 yr, HR = 4.56, 95% CI 2.84-7.31). Pulmonary exacerbations did not significantly increase the risk of chronic kidney disease (one to five exacerbations vs. none, HR = 0.79, 95% CI 0.56-1.11; six to nine exacerbations, HR = 0.92, 95% CI 0.58-1.46; ≥ 10 exacerbations, HR = 1.16, 95% CI 0.75-1.81). CONCLUSIONS: CF-related diabetes is a significant risk factor for chronic kidney disease in adults with CF, but additional studies examining IV aminoglycoside exposure directly are required.