The Use of Fibroblast Growth Factor 23 Testing in Patients with Kidney Disease

Abstract

The emergence of fibroblast growth factor 23 as a potentially modifiable risk factor in CKD has led to growing interest in its measurement as a tool to assess patient risk and target therapy. This review discusses the analytical and clinical challenges faced in translating fibroblast growth factor 23 testing into routine practice. As for other bone mineral markers, agreement between commercial fibroblast growth factor 23 assays is poor, mainly because of differences in calibration, but also, these differences reflect the variable detection of hormone fragments. Direct comparison of readout from different assays is consequently limited and likely hampers setting uniform fibroblast growth factor 23-directed targets. Efforts are needed to standardize assay output to enhance clinical use. Fibroblast growth factor 23 is robustly associated with cardiovascular and renal outcomes in patients with CKD and adds value to risk assessments based on conventional risk factors. Compared with most other mineral markers, fibroblast growth factor 23 shows better intraindividual temporal stability, with minimal diurnal and week-to-week variability, but substantial interindividual variation, maximizing discriminative power for risk stratification. Conventional therapeutic interventions for the CKD-mineral bone disorder, such as dietary phosphate restriction and use of oral phosphate binders or calcimimetics, are associated with variable efficacy at modulating circulating fibroblast growth factor 23 concentrations, like they are for other mineral metabolites. Dual therapy with dietary phosphate restriction and noncalcium-based binder use achieves the most consistent fibroblast growth factor 23-lowering effect and seems best monitored using an intact assay. Additional studies are needed to evaluate whether strategies aimed at reducing levels or antagonizing its action have beneficial effects on clinical outcomes in CKD patients. Moreover, a better understanding of the mechanisms driving fibroblast growth factor 23 elevations in CKD is needed to inform the use of therapeutic interventions targeting fibroblast growth factor 23 excess. This evidence must be forthcoming to support the use of fibroblast growth factor 23 measurement and fibroblast growth factor 23-directed therapy in the clinic.

Klotho/FGF23 Axis in Chronic Kidney Disease and Cardiovascular Disease

“…FGF23 Cterminal enzyme-linked immunosorbent assay (ELISA) yields the sum of the C-terminal fragment and intact FGF23 [74,75] , whereas FGF23 intact ELISA simply yields iFGF23, which constitutes the biological activity of FGF23 and is involved in pathophysiological processes in subjects with CKD and other phosphatemic disorders [74,76,77] . Animal studies have shown that an increase in cFGF23 by C-terminal ELISA may be due to the increase in C-terminal fragments acting as an acute-phase reactant under stressful conditions because iFGF23 was not elevated [78] .…”

The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis

“…4 FGF23 is a valuable biomarker in CKD. 5 FGF23 is a member of the FGF family which promotes negative external phosphate balance through inhibition of intestinal absorption and enhanced renal excretion. 6 Klotho protein is beta-glucuronidase which is associated with longevity, 9 cardiovascular disease, 12 and calcium/ phosphorous homeostasis in the kidney.…”

Fibroblast growth factor 23 and cardiovascular disease in chronic kidney disease; new trends

“…One of the main explanations for the high rate of mortality due to cardiac disease is various conditions such as heart calcification, diastolic dysfunction, and sudden cardiac death in patients with hypertrophy of left ventricle. The risk of sudden heart death rises with progressive loss of renal function before dialysis (3,4). Around 25% of individuals on dialysis die of sudden heart death as a one hundred increased fold risk compared to the general population.…”

“…Generally, in chronic renal failure, other major risk factors for hypertrophy of left ventricle are volume overload, anemia and hypertension. However, aggressive correction of these abnormalities leads to regression of hypertrophy of left ventricle in below than 50% of individuals on dialysis, implying the presence of some other parameters specific to chronic renal failure that are responsible for high heart and vessels disease in these group (2)(3)(4)(5). Furthermore, it is well documented that individuals with heart and vessel disease have a high risk of kidney disturbance.…”

“…It has been reported that serum fibroblast growth factor 23 levels were elevated with the induction of myocardial infarction independent of alterations in klotho and parathormone levels. Rise of serum fibroblast growth factor 23 serum levels decreased serum 1,25(OH) vitamin D levels by overwhelming the activation of 25(OH) vitamin D levels (1,4,6,7). It is also possible that aldosterone up-regulate reseals of fibroblast growth factor 23 (8).…”