Adiponectin Affects Estimated Glomerular Filtration Rate: A Two-Sample Bidirectional Mendelian Randomization Study

Background The causal relationship between adiponectin (ADPN) and estimated glomerular filtration rate (eGFR) is unclear. This study adopts a two-sample bidirectional Mendelian randomization (MR) study to explore the causal relationship between ADPN and eGFR.Methods Using eight single nucleotide polymorphisms (SNP) of ADPN and 26 SNP of eGFR as instrumental variables, the study performs a two-sample bidirectional MR study using MR inverse-variance weighted (IVW), MR-Egger and weighted median approach to evaluate the causal relationship between ADPN and eGFR. Using the genetic risk score (GRS) of ADPN and eGFR as instrumental variables, the study performs a second MR analysis to assess the association between ADPN and eGFR.Results In ADPN to eGFR MR analysis, the IVW, weighted median and GRS analysis all showed that ADPN had a causal effect on eGFR after removing potential confounders of the ADPN-eGFR relation (IVW: beta = .016, P = .002; weighted median: beta = .012, P = .022; GRS: beta = .016, P = 1.48E-05). As both ADPN and eGFR were natural log-transformed in the corresponding GWAS, eGFR increased by 0.15% for any 10% increase in ADPN. In eGFR to ADPN MR analysis, eGFR had no causal effect on ADPN after removing potential confounders of the eGFR-ADPN relation (All P values > 0.05). The heterogeneity test and sensitivity analysis indicated some heterogeneity, but no directional pleiotropy.Conclusion Adiponectin has a causal effect on eGFR, while eGFR has no causal effect on ADPN. ADPN may be a clinical target for improving eGFR and treating chronic kidney disease caused by decreased eGFR.