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Abstract: SA-PO953

Biomarker-Enriched Risk Scores and Prognostication of Kidney Outcomes Among African Americans With High-Risk APOL1 Variants

Session Information

Category: CKD (Non-Dialysis)

  • 2202 CKD (Non-Dialysis): Clinical‚ Outcomes‚ and Trials

Authors

  • Chauhan, Kinsuk, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Vasquez-Rios, George, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Naik, Nidhi, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Pattharanitima, Pattharawin, Thammasat University Faculty of Medicine, Khlong Nueng, Pathum Thani, Thailand
  • Chan, Lili, Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai Department of Medicine, New York, New York, United States
Background

Apolipoprotein L1 (APOL1) variants confer a high-risk for chronic kidney disease (CKD) among African American (AA) individuals. Adequate measures to understand abnormal pathophysiologic domains associated with this condition and risk-stratify those with high-risk APOL1 variants are lacking.

Methods

Participants with APOL1 high-risk (G1/G2 variants) genotype were selected from the Mount Sinai BioMe Biobank. Plasma TNFR1, TNFR2, KIM-1, MCP-1, YKL-40, IL-18, and suPAR were measured on banked specimens. The association between biomarkers and the composite kidney outcome (sustained ≥40% eGFR decline or ESKD during follow-up) was determined. A biomarker risk score was derived for each patient by summing the integer assigned to each biomarker tertile based on the coefficient in the hazard ratio (HR) model. The total score was divided into 8 categories and then further into low, moderate, and high-risk groups.

Results

Among 498 participants, the median age was 56 years, 67.6% were females, median eGFR was 83.3 ml/min/1.73m2, and 16.1% reached the outcome. Biomarkers were independently associated with a higher risk of the composite kidney outcome: adjusted HR per doubling for suPAR 1.7 (95% CI: 1.1-2.7), TNFR1: 2.2 (1.5-3.3), TNFR2: 1.6 (1.3-2.1), KIM-1: 1.5 (1.2-1.8), and IL-18: 1.4 (1.1-1.8). The incidence of the composite kidney outcome significantly increased with escalating risk scores. Overall, only 7% of participants in the low-risk group experienced the outcome compared with 15% in the moderate-risk group, and 33% in the high-risk group (Figure).

Conclusion

Inflammation and injury pathways may be differentially and independently associated with kidney events among patients with APOL1 high-risk variants. Measuring biomarkers may assist in risk stratification to inform during patient care and potentially serve to enrich clinical trials.

Higher biomarker risk scores show the increased risk of the composite kidney outcome