Chronic kidney disease and glaucoma: from phenotype to genotype
Chronic kidney disease and glaucoma: from phenotype to genotype
This thesis of Wei Liu explores the phenotypic and genetic associations of chronic kidney disease and uric acid with glaucoma, employing a dual-strategy design that combines large-scale population-based analyses with targeted clinical investigation. Using data from the Lifelines Cohort Study and the UK Biobank, we examined the relationships of kidney function and serum uric acid with primary open-angle glaucoma, complemented by a case-control study measuring serum and aqueous humor uric acid levels in primary angle-closure glaucoma patients.
The findings reveal that higher estimated glomerular filtration rate—rather than chronic kidney disease itself—is paradoxically associated with increased odds of primary open-angle glaucoma, challenging the conventional assumption that impaired renal function drives glaucoma risk. While serum uric acid showed a phenotypic association with primary open-angle glaucoma in meta-analysis, comprehensive genetic analyses—including linkage disequilibrium score regression, polygenic risk scores, and bidirectional Mendelian randomization—provided no evidence of shared genetic architecture or causal relationships, suggesting that uric acid is not a direct causal factor. In contrast, aqueous humor uric acid levels were significantly lower in primary angle-closure glaucoma patients compared to controls, whereas systemic levels did not differ, indicating that local ocular uric acid metabolism—rather than systemic levels—may play a role in angle-closure pathogenesis.
Collectively, these findings dissociate systemic and local mechanisms linking renal physiology to glaucoma, highlight the potential involvement of glomerular hyperfiltration in open-angle glaucoma, and underscore the importance of subtype-specific glaucoma research to unravel the complex interplay between renal function, oxidative stress, and glaucomatous optic neuropathy.