Study on Klotho and FGFR4 in Germany

In a study conducted by Sellier A.B and team, it was found that Klotho and FGFR4 were not linked to left-ventricular mass index (LVMI) or cardiac events. The findings of the study, published in the American Journal of Nephrology, do not provide evidence for a relevant clinical role of either FGFR4 stimulation or soluble form of Klotho deficiency in LVH development.

In individuals with chronic kidney disease (CKD), high plasma fibroblast growth factor 23 (FGF-23) predicts cardiovascular events. Experimental data show that FGF-23 activates FGF receptor 4 (FGFR4) and that a lack of the soluble form of its co-receptor Klotho increases left-ventricular hypertrophy (LVH).

To assess the clinical significance of these findings, Mendelian randomization research examined the correlation of FGFR4 and Klotho genetic variations with echocardiographic parameters and cardiac events in CKD patients. The prospective Cardiovascular and Renal Outcome in CKD 2–4 Patients–Fourth Homburg Evaluation research included 519 CKD G2–G4 patients, 519 of whom agreed to SNP genotyping (FGFR4: rs351855; Klotho: rs9536314). Echocardiographic tests at baseline and 5 years later were used to estimate the prevalence of LVH using the left-ventricular mass index (LVMI). For the major objectives of cardiac decompensation and atherosclerotic cardiovascular disease, patients were followed for 5.1 ± 2.1 years (ASCVD).

Carriers of the various alleles did not vary in terms of baseline LVMI or LVMI changes between baseline and follow-up. One hundred and four individuals experienced cardiac decompensation, and 144 had ASCVD. The time to cardiac decompensation and ASCVD did not differ across allele carriers.

The findings of this investigation do not support a clinical function for either FGFR4 stimulation or soluble Klotho deficiency in the development of LVH added the authors in conclusion.

Reference

Sellier A, B, Seiler-Mußler S, Emrich I, E, Böhm M, Fliser D, Zawada A, M, Heine G, H: FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease. Am J Nephrol 2021. doi: 10.1159/000519274