Introduction: Chronic kidney disease (CKD) and glaucoma are major health burdens, yet their phenotypic and genotypic relationships remain poorly understood. This population-based study aims to explore the phenotypic and genotypic relationship between CKD and glaucoma.
Methods: European-descended individuals aged 55 + from the Lifelines Cohort and UK Biobank were analyzed. Logistic regression assessed the phenotypic association of CKD and estimated glomerular filtration rate (eGFR) with glaucoma, adjusting for demographic and clinical factors. Genetic analysis included linkage disequilibrium score regression (LDSR), polygenic risk scores (PRS), and Mendelian randomization (MR).
Results: In Lifelines, no association between eGFR and glaucoma was found, but eGFR quintile 5 showed increased glaucoma risk when excluding possible cases (OR, 1.58; 95% CI, 1.07-2.23; p = 0.02). In the UK Biobank, per 10 ml/min/1.73m² eGFR increase was associated with higher glaucoma risk (OR, 1.04; 95% CI, 1.02-1.07; p = 0.001), and quintile 5 exhibited increased risk regardless of whether all cases were included (OR, 1.14; 95% CI, 1.03-1.25; p = 0.01) or possible cases were excluded (OR, 1.13; 95% CI, 1.02-1.25; p = 0.02). No significant associations were found between CKD and glaucoma. LDSR showed no genetic correlations, but PRS indicated a significant association between glaucoma PRS and higher eGFR. MR revealed no causal relationship between eGFR and glaucoma.
Conclusions: Higher eGFR is associated with increased glaucoma risk, challenging the assumed link between low eGFR and glaucoma. These findings emphasize the need for integrated nephrology-ophthalmology care to improve patient outcomes.
Key words: chronic kidney disease; glaucoma; estimated glomerular filtration rate; polygenic risk