Association between FGF23, α-Klotho, and Cardiac Abnormalities among Patients with Various Chronic Kidney Disease Stages

Abstract

BackgroundSeveral experimental studies have demonstrated that fibroblast growth factor 23 (FGF23) may induce myocardial hypertrophy via pathways independent of α-Klotho, its co-factor in the induction of phosphaturia. On the other hand, few studies have clearly demonstrated the relationship between FGF23 level and left ventricular hypertrophy among subjects without chronic kidney disease (CKD; i.e., CKD stage G1 or G2).PurposeTo investigate the data from 903 patients admitted to the cardiology department with various degrees of renal function, including 234 patients with CKD stage G1/G2.Methods and ResultsSerum levels of full-length FGF23 and α-Klotho were determined by enzyme immunoassay. After adjustment for sex, age, and estimated glomerular filtration rate (eGFR), the highest FGF23 tertile was significantly associated with left ventricular hypertrophy among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 as compared with the lowest FGF23 tertile, and the association retained significance after further adjustment for serum levels of corrected calcium, inorganic phosphate, and C-reactive protein, as well as diuretic use, history of hypertension, and systolic blood pressure. FGF23 was also associated with low left ventricular ejection fraction among patients with CKD stage G1/G2 and those with CKD stage G3a/G3b/G4 after adjusting for age, sex, eGFR, corrected calcium, and inorganic phosphate. On the other hand, compared with the highest α-Klotho tertile, the lowest α-Klotho tertile was associated with left ventricular hypertrophy and systolic dysfunction only among patients with CKD stage G3b and stage G3a, respectively.ConclusionsAn association between FGF23 and cardiac hypertrophy and systolic dysfunction was observed among patients without CKD as well as those with CKD after multivariate adjustment. However, the association between α-Klotho and cardiac hypertrophy and systolic dysfunction was significant only among patients with CKD G3b and G3a, respectively.

Fibroblast Growth Factor‐23 and Heart Failure With Reduced Versus Preserved Ejection Fraction: MESA

“…In this study, we found no significant association between higher FGF‐23 and HFrEF events, while previous studies suggested an association of higher FGF‐23 concentrations with lower LVEF 42, 43, 44. However, these studies showed very modest association with reduced EF.…”

FGF-23 and Hyperphosphatemia in Dialysis Dependent Chronic Kidney Disease Patients

“…EDV is the amount of blood in the ventricles just before systole and if it increases then eventually may cause LVH, pulmonary congestion and edema. An association between FGF23 and cardiac hypertrophy and systolic dysfunction has been observed among patients without CKD as well as those with CKD after multivariate adjustment [36]. However, present study did not reveal direct association of FGF-23 with LV function, improvement in LV function in terms of reduction in EDV was observed at six month of follow-up of the study where patients were monitored for P levels and for its control.…”

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.…”