The mechanisms of kidney–lung interactions in chronic kidney disease-associated pulmonary diseases: A two-sample Mendelian randomization study

The aim of this study was to investigate the relationship between chronic kidney disease and pulmonary diseases, and explore the mechanisms of kidney-lung interactions. Two-sample Mendelian randomization (MR) was performed to explore the causal effect of chronic kidney disease (CKD) on pulmonary diseases, and two-step MR was performed to explore the mechanisms of lung–kidney interactions in chronic kidney disease-associated pulmonary diseases. The inverse variance weighted (IVW) meta-analysis was used as the main method for obtaining the MR estimate, and complementary analysis were performed using the weighted median method, maximum-likelihood, MR-RAPS. IVW analysis showed that genetically predicted CKD was positively associated with the increased risks of asthma (OR:1.005, 95%CI:1.001, 1.009), pneumonia (OR:1.066, 95%CI: 1.009, 1.127), adult respiratory distress syndrome (ARDS) (OR:2.110, 95%CI: 1.053, 4.231), and chronic obstructive pulmonary disease (COPD) (OR, 1.004; 95%CI:1.000, 1.008). Mediation analysis revealed that interleukin-1β mediated CKD’s effect on pneumonia risk, tumor necrosis-α mediated its effects on both asthma and COPD, and parathyroid hormone (PTH) mediated its effects on pneumonia and ARDS, with mediated effects size ranging from 3.53% to 27.15%. Predicted CKD was positively associated with the increased risk of asthma, pneumonia, ARDS, and COPD. Furthermore, interleukin-1β and tumor necrosis-α, 25-hydroxyvitamin D and PTH mediated the kidney–lung interactions in CKD-associated pulmonary diseases.