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Abstract: TH-PO938

Association of Angiogenesis Markers with 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
  • Verghese, Divya Anna, Icahn School of Medicine at Mount Sinai, New York, New York, 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

Deregulated angiogenesis may play a key role in kidney disease in type 2 diabetes (T2D). We assessed the associations of 7 angiogenesis biomarkers with kidney outcomes in a contemporary clinical cohort.

Methods

We used banked plasma specimens from a cohort of patients with T2D from the EMR and USRDS-linked Mount Sinai BioMe Biobank (n=870). We measured the angiogenesis biomarkers (FLT-1, PIGF, TIE-2, VEGF, VEGF-C, VEGF-D, and bFGF) in plasma specimens banked from the time of enrollment in BioMe using the Mesoscale multiplex platform. Using multivariable Cox Regression, we evaluated the association of biomarkers with a composite kidney outcome of sustained 40% decline in eGFR or ESRD. We also examined the association between biomarker ratios (FLT-1/PIGF and combination of VEGF, VEGF-C, VEGF-D) with kidney outcomes.

Results

Median follow-up time for the population was 4.5 (IQR, 3.3-6.1) years, baseline eGFR was 68 (IQR, 55-80) ml/min/1.73 m2, and UACR was 13 (IQR, 4-66) mg/g. After adjusting for demographics, comorbidities, medications, and baseline eGFR, PIGF (adjusted HR 2.1 per doubling; 95% CI 1.5-3.1) and FLT-1 (adjusted HR 1.6 per doubling; 95% CI 1.1-2.2) were independently associated with the kidney outcomes (Figure). However, when adjusted for TNFR1, TNFR2, and KIM-1, the independent associations between biomarkers and the kidney outcomes were attenuated to null. There were no associations between the biomarker ratios and kidney outcomes.

Conclusion

Higher baseline plasma PIGF and FLT-1 are associated with kidney outcomes during follow-up in patients with T2D. Since models including TNFR1, TNFR2, and KIM-1 nullified the association of FLT-1 and PIGF with kidney outcomes, this indicates the possibilities of shared pathways between these biomarkers. More studies are needed to find a definite association between these biomarkers and kidney outcomes in T2D population.

Funding

  • NIDDK Support