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: β = .016, P = .002; weighted median: β = .012, P = .022; GRS: β = .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.