Causal relationship between chronic kidney disease and senile cataract: a bidirectional two-sample Mendelian...

Despite observed epidemiological associations, the direct causality between chronic kidney disease (CKD) and senile cataract remains unclear. This bidirectional Mendelian randomization (MR) study assessed the causal associations between CKD-including glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (UACR), dialysis, and rapid eGFR decline-and senile cataract. Summary statistics from genome-wide association studies (GWAS) of European ancestry were analyzed. Data for senile cataract comprised 404,086 individuals, while data for CKD and related kidney function traits were sourced from large-scale meta-analyses (sample size up to 1,004,040). Instrumental variables with F-statistics greater than 10 were utilized to estimate causality via inverse-variance weighted (IVW) regression, complemented by weighted median, weighted mode, and MR-Egger methods. Sensitivity analyses included MR-PRESSO for pleiotropy adjustment and Cochran's Q for heterogeneity assessment. Additionally, a multivariable MR (MVMR) analysis was conducted to adjust for type 2 diabetes (T2D). Univariable MR analyses did not support causal relationships between general CKD, eGFR, UACR, or dialysis and senile cataract. However, in the MVMR analysis adjusting for T2D, a genetically predicted rapid eGFR decline (Rapid3) was significantly associated with an increased risk of senile cataract (OR = 1.089, P = 0.014). Reverse MR analyses indicated no causal effect of senile cataract on CKD or kidney function traits. This study found no evidence for a direct causal link between general CKD and senile cataract. However, the findings suggest that rapid deterioration of kidney function may be a causal risk factor for cataract, independent of shared genetic pathways with T2D. These results underscore the clinical importance of monitoring ocular health in patients experiencing accelerated kidney function loss.