ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

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: FR-PO450

Plasma Endostatin and Kidney Outcomes in Patients with Type 2 Diabetes

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Chauhan, Kinsuk, 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
  • Chan, Lili, 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
  • Coca, Steven G., Icahn School of Medicine at Mount Sinai, New York, New York, United States
Background

Additional biomarkers are needed for prognostication of kidney function decline in patients with type 2 diabetes. There are limited data on the association of markers of endothelial dysfunction with longitudinal kidney function decline. We assessed the association of plasma endostatin, an inhibitor of angiogensesis, and kidney outcomes in two settings: a clinical trial and a contemporary clinical cohort.

Methods

We used banked plasma specimens from a nested matched case-control study (187 cases:187 controls) in the Action to Control Cardiovascular Disease (ACCORD) trial and a diverse cohort of patients with type 2 patients from the EMR and USRDS-linked Mount Sinai BioMe Biobank (n=871). We measured endostatin in plasma specimens banked from the time of enrollment in ACCORD and BioMe and examined its association with a composite kidney outcome of sustained 40% decline in eGFR or ESRD, as well as the clinical utility.

Results

Baseline eGFR was 90 ml/min/1.73 m2 in ACCORD and 66 ml/min/1.73 m2 in BioMe. Baseline plasma endostatin levels were higher for participants that achieved the composite kidney endpoint (median 42 ng/ml in 187 ACCORD cases and 45 ng/ml in 121 participants reaching the endpoint in BioMe) vs. those without the CKD endpoint in both cohorts (median 36 and 38 ng/ml, respectively). Each log2 increment in plasma endostatin was independently associated with the kidney outcome in both cohorts (adjusted OR 2.5; 95% CI 1.5-4.3 in ACCORD and adjusted HR 2.6; 95% CI 1.8-3.8). Participants in the highest quartile (>48 ng/ml in both cohorts) vs. lowest quartile of plasma endostatin (< 32 ng/ml in ACCORD and < 31 ng/ml in BioMe) had approximately 4-fold higher risk for the kidney outcome (adjusted OR 3.6; 95% CI 1.8-7.3 in ACCORD and adjusted HR 4.4; 95% CI 2.3-8.5 in BioMe). In BioMe, at a predicted probability threshold of 30% using clinical variables (age, sex, BMI, history of CVD,CHF, baseline eGFR, baseline mean arterial pressure, and ACEi/ARB usage) plus endostatin, the NPV was 0.90 (95% CI 0.89-0.91) and the PPV was 0.45 (95% CI 0.37-0.54) for the outcome of composite kidney endpoint.

Conclusion

Higher baseline plasma endostatin associated with kidney outcomes during follow-up in patients with type 2 diabetes from two diverse cohorts.

Funding

  • NIDDK Support