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Kidney Week

Abstract: FR-OR044

Rilparencel Is Associated with a Graft-Adjacent Remodeling Response and Preserved Vascular Integrity in an Immunocompromised Rat CKD Model

Session Information

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Labonte, Eric D., ProKidney LLC, Morrisville, North Carolina, United States
  • Czerwinski, Michael J., ProKidney LLC, Morrisville, North Carolina, United States
  • Cloer, Caryn M., ProKidney LLC, Morrisville, North Carolina, United States
  • Bruce, Andrew T., ProKidney LLC, Morrisville, North Carolina, United States
  • Conway, Anthony, ProKidney LLC, Morrisville, North Carolina, United States

Group or Team Name

  • Research & Development
Background

Rilparencel, an autologous cell therapy containing selected renal cells (SRC), is in a Phase 3 study (NCT05099770) for patients with advanced CKD and T2DM. To characterize entire kidney tissue effects, we evaluated an immunocompromised rat model with CKD, enabling human SRC persistence, and applied spatial along with snRNA-seq multiomic profiling

Methods

RNU rats were fed adenine to induce CKD, confirmed by biomarker and histopathology, then received kidney intracortical SRC or vehicle injection. Xenium was performed on graft-adjacent regions at Days 1, 3, & 7 to define localized host transcriptional responses near rilparencel. At Day 3, MALDI-MSI and MALDI-IHC compared the SRC injection pole against the matched contralateral pole (Fig 1A,B). At Day 28, snRNA-seq compared treatment vs vehicle kidneys

Results

Xenium showed a transcriptional response localized to graft-adjacent regions, emerging by Day 3 & evolving through Day 7, enriched for ECM remodeling & vascular development/remodeling programs. Consistent with this localized niche, Day 3 MSI identified remodeling at the SRC-parenchyma interface enriched in phospholipid species & IBA-1, PDGFR-β, vimentin, & CD44 (Fig 1C–E). By Day 28, snRNA-seq of treated vs vehicle kidneys revealed preserved peritubular vascular integrity (Nos3, Klf2, Epas1 ↑; Edn1 ↓; Fig 2A), improved proximal tubule metabolism (Cpt1a, Hmgcs2; Fig 2B) & iron buffering (Fth1, Ftl1 ↑; Fig 2C), reduced tubular injury markers (Havcr1, Spp1, Lcn2; Fig 2D), coherent TLR/NF-κB suppression (Fig 2E), & reparative macrophage polarization (Mrc1, Cd163 ↑; Fig 2F)

Conclusion

Rilparencel was associated with an early, spatially localized graft-adjacent remodeling program characterized by ECM & vascular-support transcriptional responses that evolved over the first week; at Day 28, whole-kidney transcriptomics revealed signatures of preserved vascular integrity, improved tubular metabolism, and broadly reduced injury vs vehicle

Funding

  • Commercial Support – ProKidney