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Abstract: FR-PO307

Genetically Determined Adiponectin Levels Are Associated With CKD

Session Information

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Triozzi, Jefferson Lorenzo, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wang, Guanchao, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Bick, Alexander, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States
Background

Adiponectin is a potent insulin-sensitizing hormone with multiple anti-inflammatory, anti-oxidant and anti-atherogenic properties. Insulin resistance is associated with chronic kidney disease (CKD) incidence and progression. We investigated the causal relationship between genetically determined adiponectin levels and chronic kidney disease using a mendelian randomization experiment.

Methods

We performed a mendelian randomization experiment using 12 single nucleotide polymorphisms (SNPs) from a genome wide association study of adiponectin as the exposure (ADIPOGen Consortium, n = 25,513), and CKD defined as eGFR creatinine <60 mL/min/1.73 m2 from a genome wide association study of European ancestry individuals with and without diabetes as the outcome (CKDGen, n = 12,385 cases, n = 104,780 controls). Mendelian randomization was performed using inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression analyses.

Results

Genetically predicted adiponectin levels demonstrated a causal relation with risk of chronic kidney disease in the IVW analysis (OR: 0.72, 95% CI: 0.58–0.89) and weighted median analysis (OR: 0.73, 95% CI: 0.55–0.96). Results were consistent in sensitivity analyses and there was no evidence of pleiotropy.

Conclusion

Our study finds that higher levels of adiponectin may have protective effects for CKD consistent with previous observational and pre-clinical data regarding the protective role for adiponectin in kidney disease. The mendelian randomization methodology supports a causal relationship and is less susceptible to confounding and reverse causation biases.

Funding

  • Veterans Affairs Support