Kidney Week

Abstract: TH-OR96

Endothelial-Released CD93 Predicts Poor Clinical Outcomes in Idiopathic Nephrotic Syndrome: A Study from the NEPTUNE Consortium

Session Information

• Podocytopathies and Membranous Nephropathy: Clinical Advances
  October 24, 2024 | Location: Room 1, Convention Center
  Abstract Time: 05:20 PM - 05:30 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Cara-Fuentes, Gabriel M., Nationwide Children's Hospital, Columbus, Ohio, United States

Gabriel M. Cara-Fuentes, MD, PhD

• Bauer, Colin D., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Colin D. Bauer

• Piani, Federica, Universita degli Studi di Bologna, Bologna, Emilia-Romagna, Italy

Federica Piani, MD, PhD

• Troost, Jonathan P., University of Michigan, Ann Arbor, Michigan, United States

Jonathan P. Troost, PhD

• Bjornstad, Petter, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Petter Bjornstad, MD

• Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States

Laura H. Mariani, MD, MS, FASN

• Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States

Matthias Kretzler, MD

• Sethna, Christine B., Northwell Health, New Hyde Park, New York, United States

Christine B. Sethna, MD, MEd

• Srivastava, Tarak, Mercy Health Children's Hospital, Kansas City, Missouri, United States

Tarak Srivastava, MD, FASN

• Johnson, Richard J., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States

Richard J. Johnson, MD

Background

Idiopathic nephrotic syndrome (INS) is a complex podocytopathy with highly diverse clinical trajectories. This study investigates the role of CD93, a protein primarily expressed by endothelial cells, as a predictive biomarker in INS.

Methods

We included 298 patients with INS (unbiopsied, minimal change disease -MCD-, focal segmental glomerulosclerosis -FSGS) from the NEPTUNE study. Soluble CD93 was measured in serum (n=108) and/or urine (n=228) samples, using commercial ELISA, collected at month-4 of enrollment. Mean follow-up was 38.2 months. We evaluated the relationship between soluble CD93 and 1) kidney disease progression including time to end-stage kidney disease or 40% decline in kidney function (eGFR), 2) time to complete remission, and 3) time to develop proteinuria. Kaplan-Meier curves including CD93 quartiles were used for data visualization; and Cox-Proportional hazards models (adjusting for histological diagnosis [FSGS vs. MCD] proteinuria [log transformed UPCR], and histology [interstitial fibrosis]) were used for analyses of time to event. Experimental studies were performed to identify cellular source of soluble CD93 in INS.

Results

Soluble CD93 levels were high in urine (Figure 1a) and sera from ~90% patients during relapse, irrespective of the histological pattern. Remarkably, levels remained high in ~50% patients during remission. High urinary CD93 levels associated with faster decline in kidney function (p<0.0001, Figure 1b), slower response to immunosuppression (p<0.0001), and higher risk to develop proteinuria (p=0.06). Serum CD93 levels showed no association with the studied outcomes. In cell culture studies, sera from patients in relapse, compared to controls, stimulated human glomerular endothelial cells to release CD93.

Conclusion

High urinary CD93 is a predictor of poor clinical outcomes in INS.

Funding

• Private Foundation Support