ArticleKidney research and clinical practice2023
Genetic variations in HMGCR and PCSK9 and kidney function: a Mendelian randomization study.
Article in Kidney research and clinical practice, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Moving Mendelian Randomization From Traditional Risk Factors to Molecular Targets for Drug Development and Clinical Trials in Nephrology.Kidney international reports · 2026Review
- Therapeutic monoclonal antibodies for diabetic kidney disease: a narrative review from basic mechanisms to clinical evidence.Frontiers in endocrinology · 2026Review
- Lipid-lowering drugs and risk of rapid renal function decline: a mendelian randomization study.BMC medical genomics · 2024Article
- The role of PCSK9 in glomerular lipid accumulation and renal injury in diabetic kidney disease.Diabetologia · 2024Article
- Impact of hyperuricemia on CKD risk beyond genetic predisposition in a population-based cohort study.Scientific reports · 2024Article
- Lipid-lowering and kidney.Kidney research and clinical practice · 2023Article
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Authors and funding
14 authors.
Funding
Abstract
backgroundThe genetically predicted lipid-lowering effect of HMGCR or PCSK9 variant can be used to assess drug proxy effects on kidney function.
methodsMendelian randomization (MR) analysis-identified HMGCR and PCSK9 genetic variants were used to predict the low-density lipoprotein (LDL) cholesterol-lowering effects of medications targeting related molecules. Primary summary-level outcome data for log-estimated glomerular filtration rate (eGFR; creatinine) were provided by the CKDGen Consortium (n = 1,004,040 European) from a meta-analysis of CKDGen and UK Biobank data. We also conducted a separate investigation of summary-level data from CKDGen (n = 567,460, log-eGFR [creatinine]) and UK Biobank (n = 436,581, log-eGFR [cystatin C]) samples. Summary-level MRs using an inverse variance weighted method and pleiotropy-robust methods were performed.
resultsSummary-level MR analysis indicated that the LDL-lowering effect predicted genetically by HMGCR variants (50-mg/dL decrease) was significantly associated with a decrease in eGFR (-1.67%; 95% confidence interval [CI], -2.20% to -1.13%). Similar significance was found in results from the pleiotropy-robust MR methods when the CKDGen and UK Biobank data were analyzed separately. However, the LDL-lowering effect predicted genetically by PCSK9 variants was significantly associated with an increase in eGFR (+1.17%; 95% CI, 0.10%-2.25%). The results were similarly supported by the weighted median method and in each CKDGen and UK Biobank dataset, but the significance obtained by MR-Egger regression was attenuated.
conclusionGenetically predicted HMG-CoA reductase inhibition was associated with low eGFR, while genetically predicted PCSK9 inhibition was associated with high eGFR. Clinicians should consider that the direct effect of different types of lipid-lowering medication on kidney function can vary.
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