FGF-23 but Not Klotho Predicts the Presence of Aortic Valve Calcifi cations in Moderate Chronic Kidney Disease

Background: Cardiovascular calcifi cation (CVC) is a frequent complication in chronic kidney disease (CKD) patients. Abnormalities in vitamin D receptor (VDR) activation and hyperphosphoremia are all supposed to contribute to CVC. Fibroblast Growth Factor 23 (FGF-23) is a phosphaturic glycoprotein, linked to phosphate and vitamin D metabolism as well as poor outcome in CKD. We investigated association between FGF-23 and cardiac valvular calcifi cation in moderate CKD. Methods: In this cross-sectional study, 100 (60 men; mean age of 51 ± 4.6 years) CKD stage IIIB-IV patients were enrolled and underwent laboratory (25-OH Vitamin D, Klotho, FGF-23, CRP, serum calcium and phosphorus, iPTH, phosphaturia) and echocardiography testing to assess mineral metabolism such as mitral and aortic valve calcifi cation.Parametric and non-parametric tests were used. Finally, Receiving Operating Curve (ROC) was used to test the model performance. Results: Overall mean serum calcium (9,2±0,4 mg/dl), phosphorus (4,3±0,2 mg/dl) 25OH vitamin D (34,8±13,5 ng/ml) and iPTH (59,11±8,6 pg/ml) were within the reference ranges. Serum FGF-23 and Klotho mean values were 10,4±1,7 pg/ml and 887,8±110,3 pg/ml, respectively. Phosphaturia was 1,043±258 g/day. At univariable and multivariable adjusted analyses, aortic but not mitral valve calcifi cation was associated with FGF-23 levels. Notably, Klotho, iPTH, 25OH Vitamin D, serum phosphorous, phosphaturia and CRP were not associated with either valvular calcifi cation. Conclusions: Our data suggests that FGF-23 but not Klotho is strongly and independently associated with aortic valvular calcifi cation. Future studies should test whether therapeutic strategies aimed at lowering FGF23 (diet, phosphate binders, calcimimetics) can affect calcifi cation progression and cardiovascular damage.