Assessing causal associations of FGF23 and α-Klotho with urolithiasis using Mendelian randomization analysis

Fibroblast growth factor 23 (FGF23) and α-Klotho may involve in the occurrence and development of urolithiasis. However, the underlying relationship is still unclear. Mendelian randomization (MR) analysis was performed on datasets from genome-wide association studies (GWASs) to investigate the causal relationship between FGF23, α-Klotho, and urolithiasis. The main focus was on determining the odds ratio (OR) using the inverse-variance weighted (IVW) approach. Reverse causal associations were also examined. IVW estimates suggested that a correlation between a heightened α-Klotho level and a reduced likelihood of kidney and ureter calculi (OR = 0.86, 95%CI: 0.81-0.92, P = 8.90e - 06), And reverse MR analysis revealed a unidirectional correlation (p > 0.05). However, no causal relationship was observed between FGF23 and urolithiasis. It was found that genetically predicted elevations in FGF23 (IVW OR = 0.98, 95%CI = 0.83-1.16) did not show any correlation with the likelihood of developing kidney and ureter calculi. We did not find any causal relationship between FGF23 and lower urinary tract stones (IVW OR = 0.91, 95%CI = 0.69-1.21, p = 0.529). There was no heterogeneity or pleiotropy evident in any of the results. Elevated levels of circulating α-Klotho may have a protective effect against kidney and ureter calculi. These findings could offer valuable insights into the underlying mechanisms involved in this pathway and help identify potential targets for preventing kidney and ureter calculi.