Association of serum levels of FGF23 and α-Klotho with glomerular filtration rate and proteinuria among cardiac patients

Abstract

BackgroundExpression and/or excretion of fibroblast growth factor-23 (FGF23) and its co-receptor Klotho are altered in patients with end-stage renal disease. The possibility that the FGF23/α-Klotho system mediates the aggravated cardiovascular outcome among patients with chronic kidney disease (CKD) has been suggested. We determined whether FGF23 and α-Klotho concentrations are altered among patients with reduced renal function and proteinuria.MethodsSerum FGF23 and α-Klotho were measured in cardiology patients who were not undergoing chronic hemodialysis. Estimated glomerular filtration rate (eGFR) was correlated negatively with FGF23 and positively with α-Klotho.ResultsThe correlation between FGF23 and the renal tubular maximum reabsorption rate of phosphate to the GFR (TmP/GFR) was not significant, but that between FGF23 and serum calcium or inorganic phosphate was significant among patients with an estimated GFR of less than 60 mL/min/m2. By stepwise multivariate regression analysis, eGFR was selected as significant predictor for FGF23 or α-Klotho among patients with an estimated GFR of less than 60 mL/min/m2; however, urine albumin/creatinine ratio was not selected as a predictor for FGF23 or α-Klotho irrespective of the eGFR levels. In patients with eGFR of <60 mL/min/1.73 m2, UACR was significantly associated with log(FGF23); but, this association did not remain statistically significant in a multivariate model.ConclusionsAmong cardiology patients with various stages of CKD, serum concentrations of FGF23 and α-Klotho were associated with renal function, but not with the extent of proteinuria.

Is Serum Uric Acid Independently Associated With Left Ventricular Mass Index, Ejection Fraction, and B-Type Natriuretic Peptide Among Female and Male Cardiac Patients?

“…[14][15][16][17][18] In addition, between women and men, not only mean SUA levels, but also the SUA threshold at which cardiovascular or metabolic syndrome-associated risks might increase, may vary; 19) therefore, we should analyze the data for each gender separately. In addition, the strength of the association between SUA and certain cardiac abnormalities might differ between women and men.…”

“…[4][5][6][7][8][9][10][11] Editorial p. 467 To assess whether serum SUA is associated with cardiac hypertrophy and heart failure, 12) we may have to take various possible confounders into account, such as estimated glomerular filtration rate (eGFR), phosphate, 13) and the recently identified phosphaturic hormone fibroblast growth factor 23 (FGF23) that might directly induce hypertrophy of cardiomyocytes. [14][15][16][17][18] In addition, between women and men, not only mean SUA levels, but also the SUA threshold at which cardiovascular or metabolic syndrome-associated risks might increase, may vary; 19) therefore, we should analyze the data for each gender separately. In addition, the strength of the association between SUA and certain cardiac abnormalities might differ between women and men.…”

The relationship of fibroblast growth factors 21 and 23 and α-Klotho with platelet activity measured by platelet volume indices

“…An association between FGF23 and the platelet activity markers, MPV and PWD, if present at all, may have several physiological consequences. First, considering that FGF23 increases with advancement of renal dysfunction [8] and MPV is reported to increase with progression of CKD [31], FGF23 might be involved in the increased risk of systemic thromboembolism seen among patients with CKD [32]. In the current study population, however, neither MPV nor PDW was associated with renal function (CKD stage), which might be related to the fact that patients with severe renal dysfunction (CKD stages 4/5) comprised < 10% of the study population (Table 2).…”

“…MPV and PDW were analyzed by automatic blood counter (ADVIA 2120i Hematology System; Siemens). Serumintact FGF23 was measured using a two-step FGF23 enzyme-linked immunosorbent assay (ELISA) kit (Kainos Laboratories, Tokyo, Japan), serum soluble α-Klotho was measured using a solid-phase sandwich ELISA kit (Immuno-Biological Laboratories, Gunma, Japan) [8], and serum FGF21 was measured using sandwich ELISA kit (Biovendor, Modrice, Czech Republic) according to the manufacturer's instructions.…”

“…FGF23, a bone-secreted hormone, plays a crucial role in maintaining the calcium-phosphate homeostasis together with coreceptor α-Klotho, which had originally been identified as an antiaging gene [5][6][7]. In patients with renal failure, FGF23 is increased and α-Klotho is decreased because klotho is mainly expressed in the renal tubular epithelium [8].…”