Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization
Background Metformin, widely used for type 2 diabetes, raises concerns about its use in chronic kidney disease (CKD) due to risks like lactic acidosis and renal function impact. This study uses Mendelian randomization (MR) and summary data-based MR (SMR) to explore metformin’s potential causal relat...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Renal Failure |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486551 |
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| _version_ | 1850140507116666880 |
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| author | Xiaopei Liu Xingyao Li Peng An Qi Gao Yanhong Zhao Xingmin Shi Xili Wu |
| author_facet | Xiaopei Liu Xingyao Li Peng An Qi Gao Yanhong Zhao Xingmin Shi Xili Wu |
| author_sort | Xiaopei Liu |
| collection | DOAJ |
| description | Background Metformin, widely used for type 2 diabetes, raises concerns about its use in chronic kidney disease (CKD) due to risks like lactic acidosis and renal function impact. This study uses Mendelian randomization (MR) and summary data-based MR (SMR) to explore metformin’s potential causal relationship with CKD and associated genes.Methods We employed MR methods (MR-Egger, weighted median, IVW) and sensitivity analyses to explore the causal relationship between metformin and CKD. SMR was used to analyze eQTL and CKD data from the UK Biobank and FinnGen, intersecting these with metformin drug targets to identify genes associated with CKD.Results MR analysis indicated that metformin may increase CKD risk (IVW model: OR = 144.67, p < 0.01). However, given the high OR value, additional studies are warranted to validate this finding. SMR identified genes ANPEP, STK11, ACACB, and RPS6KB as significantly associated with CKD risk.Conclusion The study suggests metformin could elevate CKD risk and identifies relevant genes. Clinicians should exercise caution when prescribing metformin, particularly for patients with renal issues. Further research is needed to confirm these findings and guide clinical practices. |
| format | Article |
| id | doaj-art-ad6766a3a94a4fdea64ee3faa8533754 |
| institution | OA Journals |
| issn | 0886-022X 1525-6049 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Renal Failure |
| spelling | doaj-art-ad6766a3a94a4fdea64ee3faa85337542025-08-20T02:29:46ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2486551Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomizationXiaopei Liu0Xingyao Li1Peng An2Qi Gao3Yanhong Zhao4Xingmin Shi5Xili Wu6Department of Traditional Chinese Medicine, Huangling Hospital of Traditional Chinese Medicine, Yan’an, Shaanxi, ChinaDepartment of Traditional Chinese Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Traditional Chinese Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Traditional Chinese Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Traditional Chinese Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaKey Laboratory for Disease Prevention and Control and Health Promotion of Shaanxi Province, School of Public Health, Medical Science Center, Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaDepartment of Traditional Chinese Medicine, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, ChinaBackground Metformin, widely used for type 2 diabetes, raises concerns about its use in chronic kidney disease (CKD) due to risks like lactic acidosis and renal function impact. This study uses Mendelian randomization (MR) and summary data-based MR (SMR) to explore metformin’s potential causal relationship with CKD and associated genes.Methods We employed MR methods (MR-Egger, weighted median, IVW) and sensitivity analyses to explore the causal relationship between metformin and CKD. SMR was used to analyze eQTL and CKD data from the UK Biobank and FinnGen, intersecting these with metformin drug targets to identify genes associated with CKD.Results MR analysis indicated that metformin may increase CKD risk (IVW model: OR = 144.67, p < 0.01). However, given the high OR value, additional studies are warranted to validate this finding. SMR identified genes ANPEP, STK11, ACACB, and RPS6KB as significantly associated with CKD risk.Conclusion The study suggests metformin could elevate CKD risk and identifies relevant genes. Clinicians should exercise caution when prescribing metformin, particularly for patients with renal issues. Further research is needed to confirm these findings and guide clinical practices.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486551Mendelian randomizationmetforminchronic kidney diseasesummary data-based Mendelian randomizationcausal relationship |
| spellingShingle | Xiaopei Liu Xingyao Li Peng An Qi Gao Yanhong Zhao Xingmin Shi Xili Wu Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization Renal Failure Mendelian randomization metformin chronic kidney disease summary data-based Mendelian randomization causal relationship |
| title | Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization |
| title_full | Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization |
| title_fullStr | Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization |
| title_full_unstemmed | Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization |
| title_short | Metformin and risk factors for chronic kidney disease in a European population based on Mendelian randomization |
| title_sort | metformin and risk factors for chronic kidney disease in a european population based on mendelian randomization |
| topic | Mendelian randomization metformin chronic kidney disease summary data-based Mendelian randomization causal relationship |
| url | https://www.tandfonline.com/doi/10.1080/0886022X.2025.2486551 |
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