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Abstract: TH-PO411

Plasma Biomarkers and the Association with Kidney Outcomes in African Americans with High-Risk Apolipoprotein L1 Variants

Session Information

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Chauhan, Kinsuk, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Verghese, Divya Anna, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Wadhwani, Shikha, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Debnath, Neha, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Chan, Lili, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

The high-risk Apolipoprotein L1 (APOL1) genotype is associated with incident and progressive chronic kidney disease (CKD) in people of African ancestry. Previous studies have demonstrated that suPAR is associated with CKD in individuals with the APOL1 high-risk genotype. We assessed the associations of suPAR and other plasma biomarkers with CKD in this population.

Methods

We measured plasma suPAR, IL-18, MCP-1 and YKL-40 in 498 BioMe Biobank participants with a high-risk APOL1 genotype. Using multivariable Cox Regression, we determined the association of these biomarkers with a composite kidney outcome of ESRD or ≥ 40% sustained decline in eGFR during the follow-up period using sequentially adjusted models.

Results

Among 498 participants, median age was 56 years, 67.7% were female and baseline eGFR was 83.3 ml/min/1.73 m2. 80 of the 498 (16.1%) experienced the composite outcome over a median of 5.9 years. After adjusting for demographics, comorbidities, medications, and eGFR, suPAR (adjusted HR 1.9 per doubling, 95% CI 1.2-3), IL-18 (adjusted HR 1.4 per doubling, 95% CI 1.1-1.9), MCP-1 (adjusted HR 1.6 per doubling, 95% CI 1.1-2.1), and YLK40 (adjusted HR 1.3 per doubling, 95% CI 1.1-1.5) were associated with increased risk of the composite kidney outcome (Figure left panel). After adjustment for 3 previously measured biomarkers (plasma TNFR1, TNFR2 and KIM-1), however, the independent associations between all 4 biomarkers and the kidney outcome were attenuated (Figure right panel).

Conclusion

Plasma suPAR, IL-18, MCP-1 and YLK40 were individually associated with kidney function decline or ESRD in individuals with high-risk APOL1 genotype. However, the relevance of these biomarkers in the setting of other commonly measured biomarkers is unclear.

Figure. Adjusted Hazard Ratio for the Kidney Endpoint per Doubling in Plasma Biomarkers

Funding

  • NIDDK Support