Causal associations of renal function and sudden sensorineural hearing loss: Evidence from a two-sample multivariable Mendelian randomization study with case–control validation

Recently, observational studies have reported an association between renal function and sudden sensorineural hearing loss (SSNHL), but the causal relationship remains unclear. To begin with, we filtered single nucleotide polymorphisms from genome-wide association studies at the summary level by implementing quality control measures in genome-wide association studies databases. Afterwards, we employed a two-sample Mendelian randomization (MR) analysis to indirectly evaluate the causal effect of renal function indicators on the risk of SSNHL. Finally, a multivariate MR approach was conducted to account for potential interactions among the positive findings. MR analysis was performed using several methods, including inverse variance weighting (IVW), maximum likelihood, weighted median, MR-Egger regression, and penalized weighted median. In addition, this study included individuals who underwent routine medical examinations at Dongzhimen Hospital, Beijing University of Chinese Medicine, from September 2004 to September 2024, and employed propensity score methodology to assess the potential causal relationship between renal function and SSNHL. In the IVW method, a significant causal relationship was found between urinary albumin excretion (UAER) and cystatin-C (Cys-C) and the risk of SSNHL (via IVW random effects: UAER [odds ratios [ORs] 0.239, 95% confidence intervals [CI] 0.071-0.813, P-value .022]; via IVW-fixed effects: UAER [OR 0.239, 95% CI 0.082-0.698, P-value .009]; Cys-C [OR 0.824, 95% CI 0.712-0.955, P-value .010]). These findings remained consistent in multivariate MR analysis, which accounted for mutual adjustments. (via IVW: UAER [OR 0.343, 95% CI 0.119-0.991, P value .048]; Cys-C [OR 0.808, 95% CI 0.697-0.936, P value .0005]). Additionally, our case-control study revealed a significant trend towards elevated Cys-C and reduced serum uric acid in patients with SSNHL. There appears to be a causal relationship between renal function and SSNHL, particularly the levels of UAER, Cys-C and serum uric acid. These findings imply that renal function should be specifically focused on in the prevention and treatment of SSNHL.