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已发表论文
探究肾功能与老年性白内障及原发性开角型青光眼发病风险之间的因果关系：一项孟德尔随机化研究及生物信息学分析
Authors Li P , Qiu T, Xu L, Wu L , Zhao S, Liu X, Yang Y, Wang J
Received 12 May 2025
Accepted for publication 13 September 2025
Published 23 September 2025 Volume 2025:18 Pages 6051—6061
DOI https://doi.org/10.2147/JMDH.S539951
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr David C. Mohr
Ping Li,1 Tingting Qiu,2 Lvjie Xu,1 Liming Wu,3 Sixuan Zhao,1 Xiao Liu,1 Yiting Yang,4 Jiawei Wang1
1Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People’s Republic of China
Correspondence: Jiawei Wang, Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email wangjw2023@126.com
Purpose: To explore causal relationships between kidney function and the risk of senile cataract and primary open-angle glaucoma (POAG) using Mendelian randomization (MR).
Methods: Summary statistics for kidney function traits were obtained from the CKDGen consortium to identify genetically predicted chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). Data on senile cataract and POAG were sourced from the FinnGen consortium. Initially, we applied the bidirectional univariate MR method (UVMR) to assess the causal effects between kidney function and the risk of senile cataract and POAG. Inverse-variance weighted method (IVW) served as the primary analysis, supplemented by weighted median and MR-Egger methods. Subsequently, multivariable MR (MVMR) was conducted to validate significant causal associations identified in UVMR. Bioinformatics analyses were conducted through enrichment analysis and a protein–protein interaction network to elucidate potential molecular mechanisms.
Results: UVMR showed that higher genetically predicted UACR was associated with an increased risk of senile cataract (IVW OR = 1.29, 95% CI: 1.05 to 1.58, P = 0.016), but no reverse causality was observed. No causal associations were found between CKD or eGFR and cataract, or between kidney function and POAG. MVMR further indicated that the associations of UACR with senile cataract remained robust after adjusting for potential confounders, including eGFR, telomere length, diabetes, hypertension, and smoking. Enrichment analysis highlighted significant associations with retinol metabolism, xenobiotic metabolism by cytochrome P450, and glycine/serine/threonine metabolism pathways.
Conclusion: Our results suggested that kidney damage, as measured by UACR, causally increased the risk of cataract, but no causal relationship was found between kidney function and POAG. This study underscores the importance of regular ophthalmic screening for individuals with albuminuria.
Keywords: senile cataract, chronic kidney disease, Mendelian randomization, primary open-angle glaucoma, urinary albumin-to-creatinine ratio
1Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Institute of Clinical Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Urology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People’s Republic of China; 4Center of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, People’s Republic of China
Correspondence: Jiawei Wang, Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China, Email wangjw2023@126.com
Purpose: To explore causal relationships between kidney function and the risk of senile cataract and primary open-angle glaucoma (POAG) using Mendelian randomization (MR).
Methods: Summary statistics for kidney function traits were obtained from the CKDGen consortium to identify genetically predicted chronic kidney disease (CKD), estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR). Data on senile cataract and POAG were sourced from the FinnGen consortium. Initially, we applied the bidirectional univariate MR method (UVMR) to assess the causal effects between kidney function and the risk of senile cataract and POAG. Inverse-variance weighted method (IVW) served as the primary analysis, supplemented by weighted median and MR-Egger methods. Subsequently, multivariable MR (MVMR) was conducted to validate significant causal associations identified in UVMR. Bioinformatics analyses were conducted through enrichment analysis and a protein–protein interaction network to elucidate potential molecular mechanisms.
Results: UVMR showed that higher genetically predicted UACR was associated with an increased risk of senile cataract (IVW OR = 1.29, 95% CI: 1.05 to 1.58, P = 0.016), but no reverse causality was observed. No causal associations were found between CKD or eGFR and cataract, or between kidney function and POAG. MVMR further indicated that the associations of UACR with senile cataract remained robust after adjusting for potential confounders, including eGFR, telomere length, diabetes, hypertension, and smoking. Enrichment analysis highlighted significant associations with retinol metabolism, xenobiotic metabolism by cytochrome P450, and glycine/serine/threonine metabolism pathways.
Conclusion: Our results suggested that kidney damage, as measured by UACR, causally increased the risk of cataract, but no causal relationship was found between kidney function and POAG. This study underscores the importance of regular ophthalmic screening for individuals with albuminuria.
Keywords: senile cataract, chronic kidney disease, Mendelian randomization, primary open-angle glaucoma, urinary albumin-to-creatinine ratio