Risk factors for longitudinal estimated glomerular filtration rate decline in adults with cystic fibrosis.

RATIONALE: In contemporary cohorts of adults with cystic fibrosis (CF), risk factors and rates of kidney function decline are unknown. With improved life expectancy, preserving kidney function is paramount to preventing early cardiovascular disease and CF-related bone disease and to maintaining eligibility for lung transplantation.

OBJECTIVES

To determine long-term kidney function decline among CF participants following the Standardized Treatment of Pulmonary Exacerbations 2 (STOP2) clinical trial and to identify specific risk factors.

METHODS

We linked participants in STOP2 with the CF Foundation Patient Registry and defined decline in kidney function as a composite of ≥40% decline in the estimated glomerular filtration rate (eGFR) or development of end-stage renal disease. We calculated the associations of risk factors such as age, diabetes status, and number of pulmonary exacerbations treated with intravenous antibiotics on decline in kidney function.

RESULTS

Among 915 STOP2 participants, the mean ± SD baseline eGFR was 114 ± 20 mL/min/1.73 m2 and 53 (6.0%) reached the composite endpoint over a median follow-up time of 3.8 years. Each 10-year increase in age was associated with a 24% greater risk of the composite outcome (hazard ratio [HR], 1.29 [95% CI, 1.01-1.65]), and participants with insulin-dependent diabetes had a greater risk of the composite endpoint (HR, 2.34 [95% CI, 1.33-4.12]). A multivariable adjusted time-updated Cox regression model demonstrated that each additional pulmonary exacerbation was associated with a greater risk of the composite outcome (HR, 1.13 [95% CI, 1.07-1.20]; P <.0001).

CONCLUSIONS

Risk factors associated with kidney function decline included age, insulin-dependent diabetes, and number of pulmonary exacerbations. These findings highlight key contributors to kidney function decline in a modern cohort of adults with CF.