FGF-23 as a predictor of renal outcome in diabetic nephropathy.
OBJECTIVE
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).


METHODS
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.
Sao Paulo University Medical School, Av Dr Enéas de Carvalho Aguiar, 255, Nephrology Department, 05403-000, São Paulo, SP, Brazil. silviatitan@superig.com.br
Silvia M
SM
Titan
Roberto
R
Zatz
Fabiana G
FG
Graciolli
Luciene M
LM
dos Reis
Rui T
RT
Barros
Vanda
V
Jorgetti
Rosa M A
RM
Moysés
D000368:Aged; D000419:Albuminuria / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001938:Brazil; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000627:therapeutic use; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D053208:Kaplan-Meier Estimate; D019808:Losartan / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D004656:Enalapril; D000089703:Fibroblast Growth Factor-23; D019808:Losartan