Abstract: FR-PO0257
Adiponectin, Leptin, APOL1 Genotypes, and Kidney Outcomes in the REGARDS Cohort
Session Information
- CKD: Omics, Systemic Stressors, and Targeted Pharmacotherapy
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Djelmami-Hani, Rayan, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
- Madere, Joseph, The University of Alabama at Birmingham School of Public Health, Birmingham, Alabama, United States
- Brooks, Marquita, The University of Alabama College of Arts and Sciences, Tuscaloosa, Alabama, United States
- Neupane, Raghavee, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
- Short, Samuel, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina, United States
- Shah, Silvi, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States
- Winkler, Cheryl Ann, National Cancer Institute Center for Cancer Research, Bethesda, Maryland, United States
- Bullen, Alexander L., University of California San Diego School of Medicine, La Jolla, California, United States
- Cheung, Katharine L., The University of Vermont Medical Center, Burlington, Vermont, United States
- Cushman, Mary, The University of Vermont Medical Center, Burlington, Vermont, United States
- Ilori, Titilayo O., Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
Background
While adiponectin is anti-inflammatory and leptin pro-inflammatory, both adipokines are paradoxically elevated in chronic kidney disease (CKD). Their roles in CKD onset and progression remain unclear, particularly in people of African ancestry, who bear a disproportionate CKD burden partly attributable to high-risk APOL1 variants. As APOL1 is modulated by inflammation, adipokines may interact with APOL1 to influence kidney outcomes. We examined leptin and adiponectin associations with incident CKD and progression, and tested APOL1 effect modification.
Methods
We analyzed the REGARDS BioMediOR sub-cohort (n=3,300; baseline eGFR ≥15 mL/min per 1.73m2, no kidney failure). Plasma adiponectin and leptin were measured by LINCOplex assay and log2-transformed. APOL1 high-risk genotype was defined as two risk alleles (G1/G1, G2/G2, or G1/G2). Incident CKD was defined as eGFR decline to <60 mL/min per 1.73m2 with ≥40% reduction from baseline or kidney failure; CKD progression as ≥40% eGFR decline or kidney failure (USRDS-linked). Modified Poisson and logistic regression estimated incident CKD RRs (adjusted for baseline eGFR) and CKD progression ORs (stratified by eGFR ≥60 or 30-60), with adipokines modeled per doubling and in quartiles. Models adjusted for age, sex, race, region, BMI, HTN, diabetes, smoking, CVD, education/income, CRP, and albuminuria. Interaction terms tested APOL1 effect modification.
Results
In fully adjusted models, both adipokines were associated with incident CKD (RR per doubling: leptin 1.04 [95% CI 1.03-1.06], adiponectin 1.05 [1.02-1.07]) and with CKD progression at eGFR ≥60 (OR per doubling: leptin 1.20 [1.18-1.22], adiponectin 1.07 [1.04-1.10]; quartile-based estimates attenuated for adiponectin; Figure 1) but not at eGFR 30-60. APOL1 modified these associations: significant interactions for adiponectin with incident CKD (p<0.001) and progression (p<0.001), and for leptin with incident CKD (p=0.01) but not progression.
Conclusion
Higher leptin and adiponectin are each associated with incident CKD and CKD progression at eGFR ≥60. APOL1 modifies these associations, supporting shared inflammatory pathways linking adipose biology, APOL1, and kidney disease.
Fully adjusted ORs; Q1 reference. Blue: eGFR ≥60; gray: eGFR 30-60.
Funding
- NIDDK Support