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Abstract: SA-PO633

Plasma Biomarkers and Renal Outcome in African Americans with High-Risk APOL1 Variants and Preserved Renal Function

Session Information

Category: Genetic Diseases of the Kidney

  • 803 Genetic Epidemiology and Other Genetic Studies of Common Kidney Diseases

Authors

  • Nadkarni, Girish N., Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • 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
  • Parikh, Chirag R., Yale University and VAMC, New Haven, Connecticut, United States
  • Do, Ron, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Horowitz, Carol, Icahn School of Medicine at Mount Sinai, New York, New York, United States
  • Bottinger, Erwin P., 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

Variants in Apolipoprotein L1 (APOL1) gene are associated with end stage renal disease (ESRD) in African Americans (AAs). However, risk stratification in AA’s with high risk APOL1 genotype (G1/G1; G2/G2 or G1/G2) is poor. We assessed the association between plasma biomarkers and renal outcomes in AAs with high-risk APOL1 genotype.

Methods

We genotyped AA BioMe Biobank participants for high-risk APOL1 genotype. We measured soluble tumor necrosis factor receptor 1/2 (sTNFR1/2) and kidney injury molecule-1 (KIM1) in plasma specimens via MesoScale Discovery multiplex assay and determined their association with a composite renal outcome of ESRD or 40% sustained decline in eGFR. We assessed improvement in area under curve (AUC) with addition of biomarkers from a baseline model using kidney failure risk equation (KFRE) with age, sex and eGFR.

Results

Among 498 APOL1 high-risk participants, median age was 56 years, 68% were female and baseline eGFR was 83 ml/min. 80 (16%) experienced the composite renal outcome over median of 6.9 years. After adjusting for age, sex and baseline eGFR, sTNFR1, sTNFR2, and KIM1 were independently associated with the renal outcome when expressed continuously or in tertiles, and in sensitivity analyses adjusting for baseline proteinuria in those with available measurements (n=209). (Table) AUC improved from 0.57 with the KFRE model to 0.74 with a biomarker-enhanced model. The event rate for participants with all 3 biomarkers in the top tertile was 40%, compared to 7% and 19% with 0 or 1 biomarker elevated, respectively (p < 0.001).

Conclusion

sTNFR1/2 and KIM1 are independently associated with renal outcome in AA’s with high-risk APOL1 genotype and improve risk discrimination. These markers can be valuable for risk stratification in AA’s with APOL1 high risk.

Associations and Discrimination for plasma biomarkers with Renal Outcome in AA’s with High Risk APOL1 Genotype
BiomarkerUnit of AnalysisAdjusted HR (95% CI)AUC for clinical model plus biomarker
sTNFR1Per log2 increment1.7 (1.3 - 2.2)0.69
3rd vs. 1st tertile4.0 (1.9 - 8.5) 
sTNFR2Per log2 increment2.6 (1.6 - 4.1)0.66
3rd vs. 1st tertile2.6 (1.3 - 5.2) 
KIM1Per log2 increment1.8 (1.3 - 2.4)0.72
3rd vs. 1st tertile3.8 (1.7 - 8.2) 
All three biomarkers NA0.74

HR- hazard ratio; AUC- area under curve

Funding

  • NIDDK Support