Prognostic Value of FGF23 in Autosomal Dominant Polycystic Kidney Disease

Abstract Introduction Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and loss of functioning renal mass, but decline in GFR and onset of ESRD occur late in the disease. Thus, there is a great need for early prognostic biomarkers in this disorder. Methods We measured baseline serum FGF23 in 192 ADPKD patients from the Consortium for Radiologic Imaging Studies of PKD (CRISP) cohort that were followed for a median of 13 years, and tested the association between FGF23 levels and change over time in height-adjusted total kidney volume (htTKV), GFR, and time to the composite endpoints of ESRD, death and doubling of serum creatinine. Results Patients in the highest quartile for baseline FGF23 level had a higher rate of increase in htTKV (0.95% per year, P=0.0016), and faster rate of decline in GFR (difference of -1.03 mL/min/1.73 m2 per year, P = 0.005) compared to the lowest quartile, after adjusting for other covariates, including htTKV and genotype. The highest quartile of FGF23 was also associated with a substantial increase in risk for the composite endpoint of ESRD, death or doubling of serum creatinine (HR 2.45 in the fully adjusted model, P = 0.03). Conclusion FGF23 is a prognostic biomarker for disease progression and clinically important outcomes in ADPKD, and has additive value to established imaging and genetic biomarkers.