Exploring the causal relationship between COPD and AKI: A bidirectional Mendelian randomization approach

Chronic obstructive pulmonary disease (COPD) and acute kidney injury (AKI) are significant public health burdens, and emerging observational studies have suggested a potential link between them. However, causality remains unclear. This study aimed to investigate the causal relationship between COPD and AKI using two-sample Mendelian randomization (MR) analyses. We utilized 11 independent single-nucleotide polymorphisms associated with COPD to perform two-sample MR analyses on 2 AKI datasets (GCST90018790 and ACUTERENFAIL). Inverse variance weighted (IVW), weighted median, MR-Egger, and weighted mode methods were employed to estimate causal effects. Sensitivity analyses included MR-Egger intercept tests for directional pleiotropy and Cochran Q tests for heterogeneity. A reverse MR analysis was also conducted using 9 AKI-associated single-nucleotide polymorphisms to assess the potential causal effect of AKI on COPD. IVW analysis indicated a significant causal effect of genetically predicted COPD on increased risk of AKI in both GCST90018790 (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.13-1.46, P = 1.19 × 10-4) and ACUTERENFAIL (OR = 1.23, 95% CI: 1.02-1.48, P = .031) datasets. The weighted median method supported these findings in the GCST90018790 dataset. No significant pleiotropy or heterogeneity was detected across sensitivity analyses. In contrast, reverse MR analyses did not reveal a causal effect of AKI on COPD (IVW OR = 0.99, 95% CI: 0.94-1.04, P = .70), with consistent null results across all methods and no evidence of pleiotropy or heterogeneity. Our findings provide genetic evidence supporting a potential causal effect of COPD on increased risk of AKI, but not vice versa. Our results suggest that COPD liability is consistent with an increased propensity for AKI, warranting further exploration of potential biological mechanisms linking pulmonary and renal dysfunction.