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Association between chronic kidney disease and age-related macular degeneration: a Mendelian randomization study
Yawei Hou1, Qinglin Liu2, Zhenwei Xiao3
1Institute of Chinese Medical Literature and Culture, Shandong University of Traditional Chinese Medicine, Jinan, China.
Insights
This study found no causal link between chronic kidney disease (CKD) and age-related macular degeneration (AMD). However, diabetic nephropathy (DN), IgA nephropathy (IgAN), and membranous nephropathy (MN) may increase AMD risk, suggesting regular eye exams for affected patients.
Area of Science:
- Ophthalmology
- Nephrology
- Genetics
Background:
- Observational studies show conflicting results on the link between chronic kidney disease (CKD) and age-related macular degeneration (AMD).
- Investigating potential causal relationships is crucial for understanding disease pathogenesis and patient management.
Purpose of the Study:
- To investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes (diabetic nephropathy [DN], immunoglobulin A nephropathy [IgAN], membranous nephropathy [MN]), and AMD in European populations.
- To clarify the etiological links between kidney function/disease and AMD subtypes.
Main Methods:
- Utilized Mendelian randomization (MR) analysis with genetic variants from genome-wide association studies (GWAS) and the FinnGen database.
- Employed the inverse-variance-weighted (IVW) method as the primary analysis, with sensitivity analyses including Cochran's Q, MR-Egger intercept, leave-one-out, and RadialMR for outlier detection.
Main Results:
- No causal association was found between CKD or eGFR and any type of AMD.
- Diabetic nephropathy (DN) showed a significant association with increased risk for early AMD, AMD, dry AMD, and wet AMD.
- Immunoglobulin A nephropathy (IgAN) was associated with increased risk for AMD and dry AMD.
- Membranous nephropathy (MN) was linked to increased risk for early AMD, AMD, and wet AMD.
Conclusions:
- This MR study found no evidence of a causal relationship between CKD and AMD.
- DN, IgAN, and MN may be risk factors for developing AMD, highlighting the importance of ophthalmological screening in patients with these conditions.
- Further research is warranted to validate these findings and elucidate the underlying mechanisms.
Purpose:
Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent.
Methods:
Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers.
Results:
IVW results showed that CKD, eGFR were not associated with any type of AMD (p > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, p = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, p = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, p = 4.87 × 10-8), IgAN (OR: 1.373, 95% CI: 1.097-1.719, p = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, p = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, p = 1.57 × 10-4) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, p = 7.55 × 10-4) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, p = 7.56 × 10-4) and MN (OR: 1.071, 95% CI: 1.040-1.103, p = 5.48 × 10-6).
Conclusion:
This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.
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