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Subjects and Methods: Using two-sample and multivariable Mendelian randomization (MR), we examined the causal effects of serum lipids and apolipoproteins on kidney function, indicated by glomerular filtration rate estimated using creatinine (eGFRcrea) or cystatin C (eGFRcys), and urinary albumin to creatinine ratio (UACR). We obtained lipid- and apolipoprotein-associated genetic variants from the Global Lipids Genetics Consortium (n=331,368) and UK Biobank (n=441,016), respectively, and kidney function markers from the Trøndelag Health Study (HUNT; n=69,736) and UK Biobank (n=464,207). The reverse causal direction was examined using variants associated with kidney function markers selected from recent genome wide association studies (GWASs).
Results: There were no strong associations between genetically predicted lipid and apolipoprotein levels with kidney function markers. Some, but inconsistent evidence suggested a weak association of higher genetically predicted atherogenic lipid levels (indicated by low-density lipoprotein cholesterol (LDL-C), triglycerides and apolipoprotein B) with increased eGFR and UACR. For high-density lipoprotein cholesterol (HDL-C), results differed between eGFRcrea and eGFRcys, but neither analysis suggested substantial effects. We found no clear evidence of a reverse causal effect of eGFR on lipid or apolipoprotein traits, but higher UACR was associated with higher LDL-C, triglyceride and apolipoprotein B levels.
Conclusion: Our MR estimates suggest that serum lipid and apolipoproteins levels do not cause substantial changes in kidney function. A possible weak effect of higher atherogenic lipids on increased eGFR and UACR warrants further investigation. Processes leading to higher UACR may lead to more atherogenic lipid levels.
|Journal||International Journal of Epidemiology|
|Publication status||Accepted/In press - 18 Jan 2021|
- Mendelian randomization
- urinary albumen to creatinine ratio