Observational epidemiology studies have revealed a bidirectional association between erectile dysfunction (ED) and impaired kidney function, but it remains uncertain whether there is a causal relationship between these two traits. In this original study, our objective was to investigate the bidirectional causal association between erectile dysfunction and kidney function biomarkers, such as creatinine-based estimated glomerular filtration rate (eGFRcrea), cystatin C-based estimated glomerular filtration rate (eGFRcys), blood urea nitrogen (BUN), serum urate, and urinary albumin-to-creatinine ratio (UACR). We also discussed the potential mechanisms that underlie this association.

Genetic instruments in the form of single-nucleotide polymorphisms (SNPs) were employed to investigate the association between kidney function traits and erectile dysfunction in a cohort of up to 1,004,040 individuals. SNPs for the latter were derived from a sample of 223,805 Europeans. Cutting-edge techniques, such as contamination mixture, inverse-variance weighted, MR-Egger, and weighted-median, were utilized in the primary analysis. Moreover, traditional Mendelian randomization (MR) approaches were employed in sensitivity analyses. Summary-level data of individuals of European ancestry were sourced from the UK Biobank and Chronic Kidney Disease Genetics Consortium.

The results of multivariable MR provided ED had a significant positive causal effect on the eGFRcrea (β =  1.004, 95% CI:1.000 – 1.008, p  =  0.030), eGFRcys (β =  0.986, 95% CI:0.973 -0.999, p  =  0.041), BUN (β =  1.013, 95% CI:1.002 - 1.024, p  =  0.014), UACR (β =  0.990, 95% CI:0.980 – 1.030, p  =  0.001). The reverse MR also showed that BUN had a significant positive causal effect on ED (OR  =  0.593, 95% CI:0.082 - 1.103, p  =  0.023)

MR leverages the principle of Mendelian inheritance, which entails the random segregation of genes during meiosis and fertilization, to infer causality between a putative exposure and a disease of interest. The MR analysis revealed a significant positive causal effect of erectile dysfunction (ED) on kidney function traits, providing evidence for a potential mechanistic association between renal dysfunction and ED.

Our study provides evidence for a possible causal effect of impaired kidney function on the development of erectile dysfunction. Specifically, we observed a potential causal relationship between creatinine-based estimated glomerular filtration rate (eGFRcrea) and urinary albumin-to-creatinine ratio (UACR) and erectile dysfunction. Several factors, such as endothelial dysfunction, oxidative stress, inflammation, and hormonal imbalances, have been proposed to contribute to the development of both kidney dysfunction and ED.  Overall, this article highlights the importance of recognizing and managing kidney dysfunction as a potential risk factor for ED, and suggests that improving kidney function may have a beneficial effect on sexual health in affected individuals. To fully understand the underlying causal relationship and the precise mechanism of action, larger-scale studies are warranted.