BACKGROUND AND OBJECTIVES: Clinically relevant kidney involvement is uncommonly described in adult patients with cystic fibrosis (CF). We sought to report on a series of patients with CF and kidney biopsy-documented renal involvement. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A retrospective study was undertaken in two referral centers for adult patients with CF in Paris, France. Patients who had undergone a biopsy of native kidneys between 1992 and 2008 were identified, and their medical records were reviewed. RESULTS: We identified 13 adult patients with CF and renal disease. Proteinuria was present in all but two cases and was associated with progressive renal impairment in four patients (median serum creatinine 85 micromol/L; range 53 to 144 micromol/L). Renal biopsy disclosed a heterogeneous spectrum of nephropathies including AA amyloidosis (n = 3), diabetic glomerulopathy (n = 3), FSGS (n = 2), minimal-change disease (n = 1), postinfectious glomerulonephritis (n = 1), IgA nephropathy related to Henoch-Schonlein purpura (n = 1), membranous nephropathy (n = 1), and chronic interstitial nephropathy (n = 1). Chronic renal failure occurred in five patients, and one patient reached ESRD. CONCLUSIONS: Although rare, clinically significant renal disease may arise in young adult patients with CF. Given the wide spectrum of diseases that may be encountered, definite diagnosis by kidney biopsy is mandatory to optimize clinical treatment of these complex patients, particularly in the perspective of organ transplantation.