ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: PO0443

Biomarkers of Immune Activation and ESKD: Results from AASK

Session Information

Category: CKD (Non-Dialysis)

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

Authors

  • Chen, Teresa K., Johns Hopkins University, Baltimore, Maryland, United States
  • Estrella, Michelle M., University of California San Francisco, San Francisco, California, United States
  • Appel, Lawrence J., Johns Hopkins University, Baltimore, Maryland, United States
  • Coresh, Josef, Johns Hopkins University, Baltimore, Maryland, United States
  • Luo, Shengyuan, Johns Hopkins University, Baltimore, Maryland, United States
  • Reiser, Jochen, Rush University, Chicago, Illinois, United States
  • Obeid, Wassim, Johns Hopkins University, Baltimore, Maryland, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
Background

Immune activation is fundamental to the pathogenesis of many kidney diseases, and innate immune molecules such as soluble urokinase-type plasminogen activator receptor (suPAR) have been linked to incidence and progression of CKD. Whether other biomarkers of immune activation are associated with ESKD in African Americans with non-diabetic kidney disease is unclear.

Methods

Utilizing baseline serum samples from AASK, we measured 4 biomarkers of immune activation (soluble tumor necrosis factor receptors 1 and 2 [sTNFR1, sTNFR2], tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]) and examined their associations with ESKD and all-cause mortality. Covariates included age, sex, systolic BP, BMI, smoking, baseline GFR and urine PCR. We also considered interactive effects of each biomarker with APOL1 risk status.

Results

Among 500 participants with available samples, mean GFR was 44.7 ml/min/1.73 m2 and median urine PCR was 0.09 g/g at baseline. Over a median follow-up 9.6 yrs, there were 161 (32%) ESKD and 113 (23%) death events. In fully adjusted models, each two-fold higher baseline level of sTNFR1, sTNFR2, and TNF-α was associated with 3.66, 2.29, and 1.35-fold greater risks of ESKD, respectively (Table). In comparison, the association between suPAR and ESKD was 1.39 (95% CI: 1.04, 1.86). These three biomarkers were also significantly associated with death (up to 2.2-fold higher risks per 2-fold higher baseline level; p≤0.01). IFN-γ was not associated with either outcome. None of the biomarkers modified APOL1-associated risks for ESKD (p-interaction>0.05). The C-statistic for the fully adjusted clinical model in predicting ESKD was excellent at 0.849 (95% CI: 0.820, 0.878). Adding sTNFR1, the biomarker with the strongest association, to the clinical model led to a small but statistically significant improvement in the C-statistic at 0.860 (95% CI: 0.833, 0.887; difference of 0.011; 95% CI: 0.001, 0.021).

Conclusion

Among African Americans with CKD attributed to hypertension, baseline levels of sTNFR1, sTNFR2, and TNF-α but not IFN-γ were associated with ESKD and mortality.

Funding

  • NIDDK Support