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Causal Effect of Low-Density Lipoprotein Cholesterol on Chronic Kidney Disease: A Mendelian Randomization Study

Dongming Zhou1, Kangchao Zheng2, Suwei Zhang1

  • 1Department of Clinical Laboratory, Shantou Central Hospital, Shantou, Guangdong, China, sthospital.com.

Biochemistry Research International
|April 8, 2026
PubMed

Insights

Low-density lipoprotein cholesterol (LDL-C) is causally linked to increased chronic kidney disease (CKD) risk. This Mendelian randomization study confirms LDL-C as an independent risk factor for CKD, even after accounting for other lipids and lifestyle factors.

Area of Science:

  • Nephrology
  • Cardiovascular Science
  • Genetics

Background:

  • Dyslipidemia is frequently observed in patients with chronic kidney disease (CKD).
  • Establishing a causal link between specific lipid profiles, like low-density lipoprotein cholesterol (LDL-C), and CKD has been challenging due to limitations in observational studies.
  • Previous Mendelian randomization (MR) studies investigating the causal relationship between LDL-C and CKD have yielded inconsistent results.

Purpose of the Study:

  • To investigate the potential causal relationship between LDL-C and CKD using a robust MR framework.
  • To evaluate the independence of the association between LDL-C and CKD, considering other lipid traits and lifestyle factors.

Main Methods:

  • A two-sample and multivariable Mendelian randomization (MVMR) approach was utilized.
  • Genetic data from the IEU Open GWAS and UK Biobank were employed for two-sample and reverse MR analyses.
  • MVMR was performed to assess the independent effect of LDL-C, adjusting for other lipids, body mass index (BMI), smoking, and alcohol consumption, with sensitivity analyses for robustness.

Main Results:

  • Two-sample MR analyses revealed a significant causal effect of higher LDL-C on increased CKD risk, with consistent findings across different data sources and no evidence of reverse causation.
  • MVMR confirmed that LDL-C remained significantly associated with CKD risk after adjusting for other lipid traits (OR=1.21, p=0.0007).
  • Further adjustment for BMI, smoking, and alcohol in the MVMR model also indicated a consistent, albeit slightly attenuated, association between LDL-C and CKD risk (OR=1.14, p=0.068).

Conclusions:

  • LDL-C may act as an independent risk factor contributing to the development or progression of CKD.
  • The independent contribution of LDL-C to CKD risk warrants further investigation and validation.
  • These findings underscore the importance of managing LDL-C levels in the context of CKD prevention and management.
Abstract

Keywords:
IEU Open GWASMendelian randomizationUK Biobankchronic kidney diseaselow-density lipoprotein cholesterol

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