Renal Impairment and Age-related Macular Degeneration: A Comprehensive Systematic Review and Meta-Analysis.

Abstract

Chronic kidney disease (CKD) and age-related macular degeneration (AMD) share vascular and inflammatory pathways. Clarifying their association could inform risk stratification across nephrology and ophthalmology. In adults with renal impairment, especially those with more advanced kidney dysfunction, closer AMD risk surveillance may be warranted, supporting integrated care between ophthalmology and nephrology even though causality cannot be fully confirmed from observational evidence alone. We systematically searched MEDLINE, Embase, Scopus, and Web of Science from inception to 11 August 2025. Eligible human observational studies and Mendelian randomization (MR) analyses assessed CKD/renal metrics (eGFR, albuminuria/proteinuria, dialysis) in relation to AMD. Random-effects meta-analyses used REML with Hartung-Knapp adjustments, and pooled evidence using odds ratios (ORs) and 95% confidence intervals (95%CI). Heterogeneity was quantified using I², subgroup analyses explored design, phenotype, and CKD severity, and small-study effects were assessed using funnel plots and Egger's test when appropriate. Certainty of evidence was rated using the GRADE prognostic-factor framework. Nineteen studies contributed to the primary meta-analysis. CKD was associated with higher odds of AMD (OR = 1.27, 95% CI 1.07-1.50; I² = 95.1%). Effects were similar by design (P for subgroup difference = 0.84): cohorts OR = 1.29 (0.98-1.69) and cross-sectional studies OR = 1.25 (0.96-1.62). By phenotype, associations were significant for non-exudative AMD (OR = 1.46, 1.06-1.99), while exudative AMD showed an imprecise increase (OR = 1.71, 0.72-4.08), and early AMD was not statistically significant (OR = 1.32, 0.90-1.93). CKD severity analyses suggested significantly higher odds with eGFR <60 mL/min/1.73 m² (OR = 1.40, 1.15-1.72), and a stronger association in dialysis ≥90 days (OR = 1.74, 1.52-2.00). Continuous renal markers aligned with a biological gradient (per SD decrease in eGFR OR = 1.30, 1.11-1.52). Two Mendelian randomization studies supported a causal association between lower eGFR and AMD (pooled OR = 1.65, 1.54-1.76). Overall certainty ranged from moderate (any AMD overall, non-exudative AMD, dialysis exposure, MR) to low/very low for most subgroups due to heterogeneity and imprecision. Renal impairment, particularly reduced eGFR (<60 mL/min/1.73 m²), elevated serum creatinine, and dialysis exposure, was associated with modestly higher odds of AMD, and the association was most consistent for non-exudative disease. A biological gradient across continuous renal markers and concordant Mendelian randomization evidence support a plausible eye-kidney link, but the very high heterogeneity (I² = 95.1%) means the pooled estimate should be read as a central tendency of a diverse evidence base rather than a precise, individually applicable risk. Causal inference therefore remains premature. In practice, these findings support integrated ocular surveillance in patients with CKD, shared vascular risk reduction across nephrology and ophthalmology, and standardized prospective studies with harmonized CKD and AMD definitions to confirm the association and clarify its direction. CRD420251123871.