#6758 THE CASUAL ASSOCIATION OF ALCOHOL CONSUMPTION AND CHRONIC KIDNEY DISEASE: A MENDELIAN RANDOMIZATION STUDY
Authors: Dekai Liu , Tang Lei , Zeng Xiaoxi , Fu Ping 
Published: June 2023

Abstract

Background and Aims
Many previous views believed that alcohol intake increases the risk of chronic kidney disease progression. Even in the previous KDIGO guidelines, alcohol restriction was included in the guidelines. However, in recent years, some research contradicted these views and removed alcohol restriction from the KDIGO guidelines. The causal relationship between alcohol intake and the risk of progression of chronic kidney disease was explored using the methods of Mendelian randomized studies.

Method
Using data from a large sample of genome-wide association studies, the Society for Genome-wide Association Analysis and Sequencing of alcohol and nicotine consumption or use (GSCAN) database (1.2 million individuals) was used to identify independent genetic loci strongly associated with alcohol consumption. Then select the corresponding genetic loci in the CKDgen consortium database (one million individuals) as instrumental variables. One is not to use “MR-PRESSO” package for analysis. Then, two sample Mendelian random methods, such as inverse variance weighting method, approximate maximum method, MR-Egger regression method, weighted median method and weighted model method, are adopted. The other one is to use “MR-PRESSO” bag to detect whether there are outlier points, remove them, and then use the inverse variance weighting method of quantity sample Mendelian random method. The causal relationship between alcohol intake and chronic kidney disease was reflected by the change in eGFR value with increased unit alcohol intake.

Results
A total of 44 single nucleotide polymorphisms (SNPS) were screened as instrumental variables. Without the use of “MR-PRESSO” package, the results obtained by using inverse variance weighting method, approximate maximum method and MR-Egger regression method were not statistically significant. The weighted median method showed that alcohol intake increased by one unit per week. The glomerular filtration rate (eGFR) was increased by 0.015ml/min (95%CI 0.005-0.026,P = 0.004). Weighted model results showed that an increase of one unit per week in alcohol intake was associated with an increase of 0.017ml/min in estimated glomerular filtration rate (eGFR) (95%CI 0.005-0.026, P = 0.002). The MR-Egger regression result showed that the genetic pleiotropy did not bias the result (intercept = 0.009,P = 0.507). However, with the removal of six outliers using MR-PRESSO, the inverse variance weighting method showed that an increase of one unit of alcohol intake per week increased the estimated glomerular filtration rate (eGFR) by 0.014ml/min (95%CI 0.010-0.020, P = 0.004).

Conclusion
This study provides an association between alcohol intake and progression of chronic kidney disease. Overall, increased alcohol intake is protective against progression of chronic kidney disease. Clinically, alcohol intake is associated with many diseases. Although this study concluded that alcohol has a protective effect on the progression of chronic kidney disease, whether increasing alcohol intake can protect kidney function needs to be treated with caution. In addition, the long-term effects of alcohol intake on the progression of chronic kidney disease also need to be studied.