Elevated Fibroblast Growth Factor 23 is a Risk Factor for Kidney Transplant Loss and Mortality

Abstract

An increased circulating level of fibroblast growth factor 23 (FGF23) is an independent risk factor for mortality, cardiovascular disease, and progression of chronic kidney disease (CKD), but its role in transplant allograft and patient survival is unknown. We tested the hypothesis that increased FGF23 is an independent risk factor for all-cause mortality and allograft loss in a prospective cohort of 984 stable kidney transplant recipients. At enrollment, estimated GFR (eGFR) was 51 Ϯ 21 ml/min per 1.73 m 2 and median C-terminal FGF23 was 28 RU/ml (interquartile range, 20 to 43 RU/ml). Higher FGF23 levels independently associated with increased risk of the composite outcome of all-cause mortality and allograft loss (full model hazard ratio: 1.46 per SD increase in logFGF23, 95% confidence interval: 1.28 to 1.68, P Ͻ 0.001). The results were similar for each component of the composite outcome and in all sensitivity analyses, including prespecified analyses of patients with baseline eGFR of 30 to 90 ml/min per 1.73 m 2 . In contrast, other measures of phosphorus metabolism, including serum phosphate and parathyroid hormone (PTH) levels, did not consistently associate with outcomes. We conclude that a high (or elevated) FGF23 is an independent risk factor for death and allograft loss in kidney transplant recipients.

A Randomized Study Evaluating Cinacalcet to Treat Hypercalcemia in Renal Transplant Recipients With Persistent Hyperparathyroidism

“…These data, support recent experimental evidence pointing to interactions between calcium and phosphorus in the regulation of FGF-23 production (50,51). Because increases of FGF-23 in renal transplant patients have been correlated with both poor graft function and patient survival (52), it is reassuring that levels remained low.…”

Competitive Interaction Between Fibroblast Growth Factor 23 And Asymmetric Dimethylarginine in Patients With CKD

“…2,5 Several cohort studies have examined the relationship between FGF-23 and renal outcomes. [10][11][12][13][14][15] In line with findings in the Chronic Renal Insufficiency Cohort cohort 11 and in the MMKD study 10 from analyses not considering the FGF-23-ADMA interaction, we confirmed that the FGF-23-CKD progression relationship was independent of (1) classic risk factors and (2) CKD-specific risk factors, such as proteinuria and the GFR, that are known to belong to the strongest predictors of CKD progression, as well as (3) major biomarkers of CKD mineral and bone disorder, including serum phosphate, 1,25(OH) 2 D, and PTH. These results further highlight the potential relevance of FGF-23 as a novel risk factor for evolution toward kidney failure in CKD.…”

“…in the United States, [11][12][13][14] as well as a large study in transplant recipients in Hungary, 15 have coherently associated high plasma FGF-23 with CKD progression toward kidney failure.…”

Bone disease after transplantation: osteoporosis and fractures risk

“…"MBD" is associated with increased morbidity and mortality in KTRs and also associated with accelerated progression of kidney disease in these patients (19). Nephrocalcinosis, a potential clinical implication of persistent HPT, may be the major cause of disordered mineral metabolism that impaired graft survival (20).…”