Intact fibroblast growth factor 23 levels predict incident cardiovascular event before but not after the start of dialysis.
ABSTRACT Low 25-hydroxyvitamin D (25D), increased levels of fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and alkaline phosphatase (ALP) were reported to be risk factors for mortality in chronic kidney disease (CKD). However, the independent associations of these factors with cardiovascular disease (CVD), the leading cause of death among CKD patients, remain unclear. Our purpose was to identify which of these factors predict incident CVD in CKD.
In this prospective cohort study, we enrolled 738 predialysis outpatients in the two nephrology departments. We employed Cox proportional hazards analyses to elucidate predictors of the endpoint, defined as fatal or non-fatal cardiovascular event requiring hospitalization. Multiple imputation was performed for missing values.
Mean estimated glomerular filtration rate (eGFR) was 35 mL/min/1.73 m(2). During a median duration of 4.4 years, 86 patients developed the endpoint, of whom 62 patients achieved it before the initiation of dialysis. Multivariable analyses revealed that high serum intact FGF23 levels predicted the outcome preceding dialysis initiation (hazard ratio (HR) per lnFGF23 (SD), 1.64 (1.27-2.30)), while 25D, PTH, and bone-specific ALP did not. Adding FGF23 to the conventional model of age, sex, diabetes, prior CVD, pulse pressure, and eGFR, led to a net reclassification improvement of 6.87% (P=0.04). Not censoring the patients at the start of dialysis and continuing follow-up even after dialysis, FGF23 levels did not predict the outcome (HR, 1.16 (0.91-1.48)). Complete case analyses yielded similar results.
Intact FGF23 levels in predialysis CKD predicted incident cardiovascular events requiring hospitalization before starting dialysis, but did not predict events during the entire follow-up period, including post dialysis initiation.
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ABSTRACT: Introduction: High phosphate levels are associated with unfavorable outcomes in ESRD. Recent data suggested that phosphate levels within the normal range are equally associated with poor outcomes in the community and CKD stage 3 - 4. Several concept papers support the potential role of phosphate load as a first-line toxin in the beginning of CKD-MBD processes via the activation of FGF23 cascade. Phosphate load is thereafter involved in the progression of vascular calcification (VC) and bone disorder typical of CKD-MBD. Areas covered: Herein the authors cover the recent evidence on the pathophysiology of phosphate handling through the natural history of CKD, with particular emphasis on FGF23 cascade, its potential surrogate markers, VC and bone disorder. The major characteristics of lanthanum carbonate are therefore discussed, focusing on its potential advantages for the treatment of difficult cases in CKD-MBD. Expert opinion: Lanthanum carbonate, being the most potent calcium-free phosphate binder available in clinical practice, could be decisive for those cases where controlling phosphate load is complicated by poor compliance to medications, stubborn high phosphorus intake, extended VC and bone disorders.Expert Opinion on Pharmacotherapy 10/2012; 13(16):2337-53. · 2.86 Impact Factor
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ABSTRACT: Elevated plasma levels of the phosphaturic hormone fibroblast growth factor 23 (FGF-23) are a hallmark of chronic kidney disease (CKD)-mineral and bone disorder. FGF-23 allows serum phosphate levels within physiological limits to be maintained in progressive CKD until end-stage renal disease is reached. Despite its seemingly beneficial role in phosphate homeostasis, several prospective studies in dialysis patients and in patients with less advanced CKD associated elevated FGF-23 with poor cardiovascular and renal outcome. Moreover, very recent evidence suggests an adverse prognostic impact of elevated FGF-23 even in subjects without manifest CKD. These epidemiological data are supplemented by laboratory findings that reveal a pathophysiological role of FGF-23 in the pathogenesis of myocardial injury. In aggregate, these clinical and experimental data identify FGF-23 as a promising target of novel therapeutic interventions in CKD and beyond, which should be tested in future clinical trials.Nephrology Dialysis Transplantation 08/2012; 27(8):3072-81. · 3.37 Impact Factor