Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis
Background: Serum uric acid (SUA) and renal status are associated with the Cardiovascular-Kidney-Metabolic (CKM) syndrome. However, the causal association among them along with drug therapy need to be explored. Methods: We employed univariable, multivariate, mediation and drug-target mendelian rando...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
|
| Series: | American Heart Journal Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666602225000904 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849330866606571520 |
|---|---|
| author | Lingyun Luo Xuelian Luo Zhen He |
| author_facet | Lingyun Luo Xuelian Luo Zhen He |
| author_sort | Lingyun Luo |
| collection | DOAJ |
| description | Background: Serum uric acid (SUA) and renal status are associated with the Cardiovascular-Kidney-Metabolic (CKM) syndrome. However, the causal association among them along with drug therapy need to be explored. Methods: We employed univariable, multivariate, mediation and drug-target mendelian randomization. Inverse variance weighting was the primary result, with extensive sensitivity analyses conducted to ensure robustness and reliability. Results: Regarding SUA, genetically predicted SUA demonstrated a potential risk effect on stage 4 of CKM syndrome (ischemic heart disease (IHD), OR = 1.090, 95 %CI: 1.003–1.184; peripheral artery disease, OR = 1.174, 95 %CI: 1.058–1.303). SUA remained a significant risk factor after excluding the confounding of eGFR and proteinuria (IHD: OR = 1.137, 95 %CI: 1.043–1.238; peripheral artery disease: OR = 1.224, 95 %CI: 1.107–1.354). SUA mediated the following causal effect: sleep apnea (2.37 %), income (1.92 %) and education (1.79 %) on IHD; C-reactive protein (11.65 %) and education (4.29 %) on peripheral artery disease. Regarding renal status, renal dysfunction led to a wider phenotype of CKM syndrome including hypertension, cerebrovascular disease, chronic kidney disease and renal failure. Similarly, renal status mediated the causal effect of education on hypertension (1.84 %), depression on cerebrovascular (0.46 %) and family history of diabetes on chronic kidney disease (3.49 %) and renal failure (2.81 %). Lesinurad targeting SLC22A11 and SLC22A12 was validated for treating IHD. Conclusion: Our study clarified the complex relationship among SUA, renal status and CKM syndrome. Simultaneously providing innovative drug and social interventions for CKM syndrome. |
| format | Article |
| id | doaj-art-2d70d946e66f4d64ad067f8565124baa |
| institution | Kabale University |
| issn | 2666-6022 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | American Heart Journal Plus |
| spelling | doaj-art-2d70d946e66f4d64ad067f8565124baa2025-08-20T03:46:47ZengElsevierAmerican Heart Journal Plus2666-60222025-09-015710058710.1016/j.ahjo.2025.100587Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysisLingyun Luo0Xuelian Luo1Zhen He2Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China; Hubei Provincial Engineering Research Center of Vascular Interventional Therapy, Wuhan 430030, Hubei, ChinaDepartment of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China; Corresponding authors.Department of Cardiac Surgical Intensive Care Unit, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, China; Corresponding authors.Background: Serum uric acid (SUA) and renal status are associated with the Cardiovascular-Kidney-Metabolic (CKM) syndrome. However, the causal association among them along with drug therapy need to be explored. Methods: We employed univariable, multivariate, mediation and drug-target mendelian randomization. Inverse variance weighting was the primary result, with extensive sensitivity analyses conducted to ensure robustness and reliability. Results: Regarding SUA, genetically predicted SUA demonstrated a potential risk effect on stage 4 of CKM syndrome (ischemic heart disease (IHD), OR = 1.090, 95 %CI: 1.003–1.184; peripheral artery disease, OR = 1.174, 95 %CI: 1.058–1.303). SUA remained a significant risk factor after excluding the confounding of eGFR and proteinuria (IHD: OR = 1.137, 95 %CI: 1.043–1.238; peripheral artery disease: OR = 1.224, 95 %CI: 1.107–1.354). SUA mediated the following causal effect: sleep apnea (2.37 %), income (1.92 %) and education (1.79 %) on IHD; C-reactive protein (11.65 %) and education (4.29 %) on peripheral artery disease. Regarding renal status, renal dysfunction led to a wider phenotype of CKM syndrome including hypertension, cerebrovascular disease, chronic kidney disease and renal failure. Similarly, renal status mediated the causal effect of education on hypertension (1.84 %), depression on cerebrovascular (0.46 %) and family history of diabetes on chronic kidney disease (3.49 %) and renal failure (2.81 %). Lesinurad targeting SLC22A11 and SLC22A12 was validated for treating IHD. Conclusion: Our study clarified the complex relationship among SUA, renal status and CKM syndrome. Simultaneously providing innovative drug and social interventions for CKM syndrome.http://www.sciencedirect.com/science/article/pii/S2666602225000904Serum uric acidRenal statusCardiovascular-kidney-metabolic syndromeMendelian randomization |
| spellingShingle | Lingyun Luo Xuelian Luo Zhen He Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis American Heart Journal Plus Serum uric acid Renal status Cardiovascular-kidney-metabolic syndrome Mendelian randomization |
| title | Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis |
| title_full | Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis |
| title_fullStr | Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis |
| title_full_unstemmed | Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis |
| title_short | Serum uric acid, renal status, cardiovascular-kidney-metabolic syndrome and drug therapy, a wide-angled Mendelian randomization analysis |
| title_sort | serum uric acid renal status cardiovascular kidney metabolic syndrome and drug therapy a wide angled mendelian randomization analysis |
| topic | Serum uric acid Renal status Cardiovascular-kidney-metabolic syndrome Mendelian randomization |
| url | http://www.sciencedirect.com/science/article/pii/S2666602225000904 |
| work_keys_str_mv | AT lingyunluo serumuricacidrenalstatuscardiovascularkidneymetabolicsyndromeanddrugtherapyawideangledmendelianrandomizationanalysis AT xuelianluo serumuricacidrenalstatuscardiovascularkidneymetabolicsyndromeanddrugtherapyawideangledmendelianrandomizationanalysis AT zhenhe serumuricacidrenalstatuscardiovascularkidneymetabolicsyndromeanddrugtherapyawideangledmendelianrandomizationanalysis |