FGF-23 as a predictor of renal outcome in diabetic nephropathy
Silvia M Titan, Roberto Zatz, Fabiana G Graciolli, Luciene M dos Reis, Rui T Barros, Vanda Jorgetti, Rosa M A Moysés, Silvia M Titan, Roberto Zatz, Fabiana G Graciolli, Luciene M dos Reis, Rui T Barros, Vanda Jorgetti, Rosa M A Moysés
Abstract
Background and objectives: Fibroblast growth factor 23 (FGF-23) has emerged as a new factor in mineral metabolism in chronic kidney disease (CKD). An important regulator of phosphorus homeostasis, FGF-23 has been shown to independently predict CKD progression in nondiabetic renal disease. We analyzed the relation between FGF-23 and renal outcome in diabetic nephropathy (DN).
Design, setting, participants, & measurements: DN patients participating in a clinical trial (enalapril+placebo versus enalapril+losartan) had baseline data collected and were followed until June 2009 or until the primary outcome was reached. Four patients were lost to follow-up. The composite primary outcome was defined as death, doubling of serum creatinine, and/or dialysis need.
Results: At baseline, serum FGF-23 showed a significant association with serum creatinine, intact parathyroid hormone, proteinuria, urinary fractional excretion of phosphate, male sex, and race. Interestingly, FGF-23 was not related to calcium, phosphorus, 25OH-vitamin D, or 24-hour urinary phosphorus. Mean follow-up time was 30.7±10 months. Cox regression showed that FGF-23 was an independent predictor of the primary outcome, even after adjustment for creatinine clearance and intact parathyroid hormone (10 pg/ml FGF-23 increase = hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P=0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of >70 pg/ml.
Conclusions: FGF-23 is a significant independent predictor of renal outcome in patients with macroalbuminuric DN. Further studies should clarify whether this relation is causal and whether FGF-23 should be a new therapeutic target for CKD prevention.
Trial registration: ClinicalTrials.gov NCT00419835.
Figures
Source: PubMed