Appraising the causal relationship between kidney function and hearing performance: a two-sample Mendelian...

Epidemiological studies have reported an association between chronic kidney disease and hearing impairment, but the causal relationship remains uncertain. We conducted a bidirectional two-sample Mendelian randomization study to examine whether genetically predicted kidney function traits causally influence speech reception threshold, an objective measure of auditory performance. Genetic instruments for estimated glomerular filtration rate, chronic kidney disease, and blood urea nitrogen were obtained from large-scale genome-wide association studies conducted by the CKDGen Consortium, and summary statistics for speech reception threshold in the left and right ears were derived from the UK Biobank. The inverse variance weighted method was used as the primary analytical approach, complemented by MR-Egger, weighted median, and mode-based estimators. No robust causal associations were identified between genetically predicted kidney function traits and SRT in either ear. IVW estimates for BUN, CKD, and eGFR were non-significant (all P > 0.05). Although the IVW estimate for eGFR and left-ear SRT approached nominal significance and some secondary analyses showed nominal associations, these findings were inconsistent across methods and did not meet our criteria for robust causal inference. Reverse Mendelian randomization analyses also showed no significant associations. Sensitivity analyses showed no evidence of directional horizontal pleiotropy, and outlier correction did not materially change the results. This study provides no robust genetic evidence supporting a causal relationship between genetically predicted kidney function traits and hearing function, as measured by speech reception threshold, in either direction under the current MR framework. The observed epidemiological association may instead reflect shared systemic, developmental, or environmental mechanisms.