#6774 CAUSAL ASSOCIATION OF COVID-19 AND KIDNEY FUNCTION: A MENDELIAN RANDOMIZATION ANALYSIS

Abstract Background and Aims Previous observational studies suggest that there are potential relationships between COVID-19 and kidney functions. However, whether COVID-19 had causal effects on different kidney traits is currently unclear. We aimed to investigate the causal link between genetically determined COVID-19 and following kidney traits. Method We performed univariate Mendelian randomization (MR) studies using summary genome-wide association studies (GWAS) statistics of COVID-19 severity (n case/n control: 13,769/1,072,442 for European, n case/n control: 794/4862 for Asian), COVID-19 hospitalization (n case/n control: 32,519/2,062,805 for European, n case/n control:2882/31,200 for Asian) and COVID-19 susceptibility (n case/n control: 122,616/2,475,240 for European, n case/n control: 4459/36,121 for Asian) derived from THE COVID-19 Host Genetics Initiative (r7) as exposure. Phenotypic outcomes analyzed for Europeans included chronic kidney disease (CKD), creatinine-based estimated glomerular filtration rate, Cystatin C-based estimated glomerular filtration rate, Urine albumin-to-creatinine ratio, acute and chronic glomerulonephritis, membranous nephropathy, diabetic nephropathy, acute and chronic nephritic syndrome, acute renal failure, glomerular diseases and IgA nephropathy. While for Asians, outcomes including CKD, estimated glomerular filtration rate, serum creatinine, acute and chronic renal failure, diabetic nephropathy, IgA nephropathy, nephrotic syndrome, acute and chronic glomerulonephritis as well as membranous nephropathy were analyzed. The inverse variance weighted (IVW) MR with multiplicative random effects model was performed as primary analysis to evaluate the causal effects of COVID-19 on different kidney traits, and potential pleiotropy as well as heterogeneity was evaluated by using MR Egger and heterogeneity test, respectively. A series of sensitivity analyses, including weighted median MR, weighted mode MR, MR Pleiotropy Residual Sum and Outlier (MR PRESSO) were performed. In addition, the causal effects of COVID-19 on different kidney traits were validated by using additional GWAS summary data of critical COVID-19 (n case/n control: 5989/42891 for European, n case/n control: 274/366 for Asian) from GenOMICC database (r6) as exposure. After multiple corrections, a P value < 0.0036 for Europeans and P value < 0.0045 for Asians were considered as significant. Results IVW MR indicated that none of the COVID-19 phenotypes were associated with CKD (OR, 0.99: P = 0.16 for COVID-19 severity; OR, 0.99: P = 0.41 for COVID-19 hospitalization; OR, 0.95: P = 0.26 for COVID-19 susceptibility), nor other kidney traits for Europeans. As for Asian ancestry, consistent with the findings in Europeans, none of the COVID-19 phenotypes were associated with CKD (OR, 0.89: P = 0.16 for COVID-19 severity; OR, 0.93: P = 0.42 for COVID-19 hospitalization; OR, 0.95: P = 0.61 for COVID-19 susceptibility), nor other kidney traits as mentioned above. All sensitivity analyses also consistently indicated the absence of causal effects of COVID-19 severity, hospitalization and susceptibility on different kidney traits, neither in the European nor in the Asian population. Conclusion There is no significant evidence supporting the causal effects of genetically predicted COVID-19 phenotype on the following different kidney traits. More deeply explorations focused on the association between COVID-19 and kidney traits should be performed with more data would be available in the future.