Kidney Week

Abstract: SA-PO263

Late Clinical-Stage Candidate Rilparencel's Effect on Kidney Function and Biological Pathways in a Type 2 Diabetes and CKD Patient Subset

Session Information

• Diabetic Kidney Disease: Basic - 2
  October 26, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 701 Diabetic Kidney Disease: Basic

Authors

• Narayan, Prakash, ProKidney, Winston-Salem, North Carolina, United States

Prakash Narayan, PhD

• Bauer, Brooke, ProKidney, Winston-Salem, North Carolina, United States

Brooke Bauer

• Filler, Guido, Western University, London, Ontario, Canada

Guido Filler, MD, PhD

• Freedman, Benjamin S., University of Washington, Seattle, Washington, United States

Benjamin S. Freedman, PhD

• Trachtman, Howard, Renal Strategies LLC, New York, New York, United States

Howard Trachtman, MD, FASN

• Stavas, Joseph, ProKidney, Winston-Salem, North Carolina, United States

Joseph Stavas, MD, MPH

• Butler, Emily Lynn, ProKidney, Winston-Salem, North Carolina, United States

Emily Lynn Butler, PhD

• Bruce, Andrew T., ProKidney, Winston-Salem, North Carolina, United States

Andrew T. Bruce

Background

Kidney cortical biopsy-derived rilparencel is a 1^st-in-class autologous kidney epithelial cell platform being evaluated in late-stage clinical trials for patients with type 2 diabetes (T2D) & chronic kidney disease (CKD). Data from 2 Phase 2 studies suggest that kidney cortical injection of rilparencel may preserve estimated glomerular filtration rate (eGFR). In a proof-of-concept, limited retrospective cohort study we sought to evaluate biological pathways associated with rilparencel’s effect on kidney function.

Methods

Banked rilparencel samples from 5 patients with T2D&CKD (NCT02836574) were analyzed with scRNAseq. Kidney cell types were identified with unsupervised clustering & projection on to the KPMP atlas. For each rilparencel cell type, cell-level & pseudo-bulk differentially expressed genes (DEGs) were identified by Wilcoxon Rank Sum test & DESeq2, respectively, based on each patient’s response to rilparencel, i.e. eGFR slope computed across 12 mo post-treatment. Biological pathways were identified with GO.

Results

KPMP-anchored molecularly profiled kidney cell types in rilparencel include glomerular parietal epithelial cells (PECs), adaptive proximal tubules (PT), ascending thin limb (ATL) & adaptive thick ascending limb-2 (TAL-2), distal convoluted tubule, connecting tubule & intermediate collecting ducts (DCT/CNT/IMCD). For each cell type, DEGs correlating with renal function were identified. Increased epithelial cell differentiation (PEC), negative regulation of inflammatory response genes (PT), increased expression of cell migration genes within Loop of Henle limbs & decreased cell adhesion (DCT/CNT/IMCD) appear to exhibit improved eGFR slopes.

Conclusion

In a limited retrospective cohort of T2D&CKD patients reparative & restorative pathways can be detected with rilparencel’s effect on kidney function. Our approach might serve as a roadmap for unveiling the mechanism of action of cell-based therapies.

Funding

• Commercial Support – ProKidney