Association Between Chronic Kidney Disease and Glaucoma: Results from the Lifelines Cohort Study and UK Biobank

Purpose: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:In this cross-sectional study, European-descended individuals aged 55 years + from the Lifelines Cohort (n = 21,475; 906 CKD cases) and UK Biobank (n = 90,133; 3323 CKD cases) were analyzed. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². In Lifelines, glaucoma was defined using a previously established algorithm, which integrated self-reported glaucoma diagnosis and treatment with NEI-VFQ-25 scores. In the UK Biobank, primary open angle glaucoma cases were identified using a combination of self-reported diagnoses, treatment history, and International Classification of Diseases (ICD) codes. Logistic regression assessed the phenotypic association of CKD and 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:The prevalence of glaucoma was 8.2% in Lifelines and 5.5% in the UK Biobank. In Lifelines, no association between eGFR and glaucoma was found, but eGFR quintile 5 showed increased odds of glaucoma when excluding possible cases (odds ratio [OR] = 1.58, 95% confidence interval [CI] = 1.07-2.23, P = 0.02). In the UK Biobank, per 10 mL/min/1.73 m² eGFR increase was associated with higher odds of glaucoma (OR = 1.04, 95% CI = 1.02-1.07, P = 0.001), and quintile 5 exhibited increased odds 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:No association was found between CKD and glaucoma, but higher eGFR was associated with increased odds of glaucoma. These findings challenge the assumed link between low eGFR and glaucoma and highlight the need for further research into the underlying mechanisms and potential clinical implications of this association.