Kidney Week

Abstract: SA-PO354

Selected Renal Cells Improve Renal Function in a Canine Model of CKD

Session Information

• Development, Organoids, Vascularized Kidneys, Nephrons, and More
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 600 Development, Stem Cells, and Regenerative Medicine

Authors

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

Prakash Narayan,

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

Andrew T. Bruce,

• Rivera, Elias A., ProKidney, Winston-Salem, North Carolina, United States

Elias A. Rivera,

• Bertram, Tim A., ProKidney, Winston-Salem, North Carolina, United States

Tim A. Bertram,

• Jain, Deepak, ProKidney, Winston-Salem, North Carolina, United States

Deepak Jain,

Background

Selected renal cells (SRCs) express podocyte, ureteric bud and cap mesenchyme markers associated with glomerular barrier function, renal filtration and urine concentration. In the present study we tested the hypothesis that cortical administration of autologous SRCs improves renal filtration and preserves renal microarchitecture in the canine subtotal nephrectomy (Nx) model of renal hypertensive chronic kidney disease.

Methods

SRCs were sourced from the excised contralateral kidneys of adult male mongrel dogs subjected to Nx. At weeks 15 and 43 post Nx, dogs were administered SRCs (~300x10⁶ cells/dog into the remnant renal cortex, n=4) or placebo (n=4). Renal filtration was monitored over weeks 44 through 57 and renal microarchitecture (Masson’s Trichrome) evaluated at sacrifice. A sham cohort served as control.

Results

There was no difference between the two Nx cohorts prior to randomization. SRC treatment was associated with increased body weight (p<0.01), reduced urine protein (p<0.01) and urine protein to creatinine ratio (p<0.01), and improved serum albumin (p<0.01) and creatinine clearance profiles (p<0.05, A-D). SRCs did not reduce blood pressure, rather their activity appeared to be directly related to preservation of renal microarchitecture evidenced by reduced - glomerular hypertrophy, tubular dilatation, cast deposition, inflammation and fibrosis (E).

Conclusion

These data suggest that SRCs, a standalone cell-based platform, has anti-inflammatory and anti-fibrotic activity and preserves glomerular and tubular microarchitecture and improves multiple indices of renal function in a large animal model of renal disease.

SRCs improve renal filtration (A-D) and preserve renal microarchitecture (E) in a canine model of hypertensive chronic kidney disease.

Funding

• Commercial Support – ProKidney