FGF-23 as a Predictor of Renal Outcome in Diabetic Nephropathy

Abstract

SummaryBackground 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 (enalaprilϩplacebo versus enalaprilϩlosartan) 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 Ϯ 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 ϭ hazard ratio, 1.09; 95% CI, 1.01 to 1.16, P ϭ 0.02). Finally, Kaplan-Meier analysis showed a significantly higher risk of the primary outcome in patients with FGF-23 values of Ͼ70 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.

Combined Use of Vitamin D Status and FGF23 for Risk Stratification of Renal Outcome

“…For example, hyperphosphatemia, high serum parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) levels, and vitamin D deficiency were reported to be risk factors for mortality and cardiovascular events in patients with CKD, especially in dialysis patients (2)(3)(4)(5)(6)(7). Recently, these derangements were reported to be associated with CKD progression (8)(9)(10)(11)(12)(13).…”

FGF-23: estado da arte

“…Another interesting result is that hyperphosphatemia occurred only in 12% of the patients, all of whom had glomerular filtration rate lower than 30 mL/min. 44 Clinical studies have shown an association of high FGF-23 levels and CKD progression, 45,46 development of severe secondary hyperparathyroidism, 47 left ventricle hypertrophy, 48 and mortality. 49 A recent study with 177 nondiabetic patients with serum creatinine ranging from 0.9 to 4.9 mg/dL, followed up for a mean period of 53 months, has reported that FGF-23 was a predictor of the progression of renal disease as important as glomerular filtration rate.…”

“…45 In another study with 55 patients with stage III diabetic nephropathy with macroalbuminuria followed up for a mean period of 30.7 months, the FGF-23 level was also an isolated predictive factor for the evolution of diabetic nephropathy, regardless of the levels of P, Ca, PTH, and 25(OH) 2 D 3 . 46 The hypothesis that high FGF-23 levels are associated with secondary hyperparathyroidism has been demonstrated in a study with 103 patients undergoing hemodialysis. By the end of two years, patients who had high FGF-23 levels at the beginning of the study developed more severe forms of secondary hyperparathyroidism, independently of the initial PTH levels.…”

“…However, in the long run, excessive FGF-23 could favor negative clinical outcomes, such as the development of secondary hyperparathyroidism, rapid progression to CKD, and a higher mortality rate. [45][46][47][48][49][50] Thus, modulating serum FGF-23 levels can benefit patients, reducing adverse events, especially those related to disorders of the bone and mineral metabolism.…”

“…52 Knowing that Ca overload influences FGF-23 levels can have implications with important clinical outcomes, such as mortality and cardiovascular disease, since several studies have shown the association between high FGF-23 levels and those clinical outcomes. [45][46][47][48][49][50] Considering all those unanswered questions, a recent review on the topic draws attention to the importance of better understanding the role played by P and FGF-23 in CKD, proposing to the nephrological community a randomized, controlled, long-term study using P binders in the early phases of CKD, and analyzing clinical outcomes, such as vascular calcification, bone health, and CKD progression. 69 conclusIons Several studies have consolidated the role of P as a potentially toxic element, associated with increased mortality rate.…”