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

Area of Science:

• Nephrology
• Ophthalmology
• Genetics

Background:

• Epidemiological studies suggest a link between chronic kidney disease (CKD) and senile cataract, but direct causality remains unproven.
• Understanding this relationship is crucial for patient management and disease prevention.

Purpose of the Study:

• To investigate the causal associations between CKD (including eGFR, UACR, dialysis, and rapid eGFR decline) and senile cataract using a bidirectional Mendelian randomization approach.
• To determine if senile cataract causally influences CKD or kidney function.

Main Methods:

• Utilized summary statistics from large-scale genome-wide association studies (GWAS) for senile cataract and CKD traits in European ancestry.
• Employed inverse-variance weighted (IVW) regression, weighted median, weighted mode, and MR-Egger methods for causal estimation.
• Conducted sensitivity analyses (MR-PRESSO, Cochran's Q) and multivariable MR (MVMR) adjusting for type 2 diabetes (T2D).

Main Results:

• Univariable Mendelian randomization (MR) analyses found no significant causal links between general CKD, eGFR, UACR, or dialysis and senile cataract.
• Multivariable MR analysis, after adjusting for T2D, revealed a significant association between genetically predicted rapid eGFR decline and increased risk of senile cataract (OR=1.089, P=0.014).
• Reverse MR analyses showed no evidence of a causal effect of senile cataract on CKD or kidney function.

Conclusions:

• There is no direct causal relationship established between chronic kidney disease and senile cataract.
• Rapid deterioration of kidney function emerges as a potential causal risk factor for cataract, independent of shared genetic factors with T2D.
• Clinical monitoring of ocular health is recommended for individuals experiencing accelerated loss of kidney function.