Abstract
BackgroundHigh levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR.MethodsFollowing approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were expressed as median (25th, 75th percentile).ResultsFGF23 correlated significantly with CysC, CysC eGFR, PTH, 1.25 (OH)2 vitamin D, phosphate, and pH. The correlation of the latter three remained significant in the multivariate analysis. We calculated a formula for the expected FGF23 value for a given level of eGFR which reads Y = 1295 * e-0.07247*X + 38.35. Deviation by more than 20% from the curve also depended on phosphate, 1.25 (OH)2 vitamin D and pH.ConclusionsOur data emphasize the importance of phosphate and 1.25 (OH)2 vitamin D levels. The impact of acidosis on FGF23 warrants further studies.
Highlights
High levels of fibroblast growth factor-23 (FGF23) are associated with mortality
[1] It exponentially rises with worsening kidney function and is strongly associated with cardiovascular morbidity [2,3,4,5,6,7] and mortality in patients with chronic kidney disease (CKD). [8, 9] FGF23 strongly correlates with glomerular filtration rate (GFR) [10, 11] and cystatin C (CysC) in particular
It is not yet clear whether higher FGF23 levels occur as a: (i) compensatory response to decreased renal capacity to excrete phosphate [13,14,15]; (ii) result of the use of calcium-based phosphate binders [16]; (iii) result of decreased 1,25 vitamin D3 levels; (iv) result of secondary hyperparathyroidism [17]; (v) or whether this is related to the disease process of CKD alone, as low molecular weight proteins (LMWPs) blood concentrations are greatly influenced by the GFR. [12, 18, 19] nutritional factors and uremic toxins may increase FGF23-concentrations. [20, 21] The objective of the current manuscript was to determine expected FGF23 levels for given levels of CysC GFR and to determine which other parameters would be associated with a deviation in FGF23 concentrations
Summary
High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. [12] Both FGF23 and CysC are low molecular weight proteins (LMWPs) that accumulate with worsening GFR. It is not yet clear whether higher FGF23 levels occur as a: (i) compensatory response to decreased renal capacity to excrete phosphate [13,14,15]; (ii) result of the use of calcium-based phosphate binders [16]; (iii) result of decreased 1,25 vitamin D3 levels; (iv) result of secondary hyperparathyroidism [17]; (v) or whether this is related to the disease process of CKD alone, as LMWP blood concentrations are greatly influenced by the GFR. It is not yet clear whether higher FGF23 levels occur as a: (i) compensatory response to decreased renal capacity to excrete phosphate [13,14,15]; (ii) result of the use of calcium-based phosphate binders [16]; (iii) result of decreased 1,25 vitamin D3 levels; (iv) result of secondary hyperparathyroidism [17]; (v) or whether this is related to the disease process of CKD alone, as LMWP blood concentrations are greatly influenced by the GFR. [12, 18, 19] nutritional factors and uremic toxins may increase FGF23-concentrations. [20, 21] The objective of the current manuscript was to determine expected FGF23 levels for given levels of CysC GFR and to determine which other parameters would be associated with a deviation in FGF23 concentrations.
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