Exploring Causal Relationships Between Kidney Function and the Risk of Senile Cataract and Primary Open-Angle Glaucoma: A Mendelian Randomization Study and Bioinformatics Analyses.

Abstract

Purpose: To explore causal relationships between kidney function and the risk of senile cataract and primary open-angle glaucoma (POAG) using Mendelian randomization (MR).

Methods: Summary statistics for kidney function traits were obtained from the CKDGen consortium to identify genetically predicted chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). Data on senile cataract and POAG were sourced from the FinnGen consortium. Initially, we applied the bidirectional univariate MR method (UVMR) to assess the causal effects between kidney function and the risk of senile cataract and POAG. Inverse-variance weighted method (IVW) served as the primary analysis, supplemented by weighted median and MR-Egger methods. Subsequently, multivariable MR (MVMR) was conducted to validate significant causal associations identified in UVMR. Bioinformatics analyses were conducted through enrichment analysis and a protein-protein interaction network to elucidate potential molecular mechanisms.

Results: UVMR showed that higher genetically predicted UACR was associated with an increased risk of senile cataract (IVW OR = 1.29, 95% CI: 1.05 to 1.58, P = 0.016), but no reverse causality was observed. No causal associations were found between CKD or eGFR and cataract, or between kidney function and POAG. MVMR further indicated that the associations of UACR with senile cataract remained robust after adjusting for potential confounders, including eGFR, telomere length, diabetes, hypertension, and smoking. Enrichment analysis highlighted significant associations with retinol metabolism, xenobiotic metabolism by cytochrome P450, and glycine/serine/threonine metabolism pathways.

Conclusion: Our results suggested that kidney damage, as measured by UACR, causally increased the risk of cataract, but no causal relationship was found between kidney function and POAG. This study underscores the importance of regular ophthalmic screening for individuals with albuminuria.