Renal cell transplantation reverses PKD progression (1180.22)

Abstract

Polycystic kidney disease (PKD, including ADPKD1, ADPKD2, ARPKD) are diseases with overlapping phenotypes and are not curable. They can progress to ESRD, and then the only hope to get off of dialysis is kidney transplantation. We have introduced intravenous renal cell transplantation (IRCT) in rats as an alternative to kidney transplantation, and tested the hypothesis that IRCT with Serum Amyloid A protein (SAA) expressing normal adult renal cells improves structure and function in PKD by coordinating the re‐orientation of adjacent host PKD cells. We tested this idea in the PCK rat, an orthologus model of ARPKD. We included six rat groups starting with surgery at 6 weeks of age and IRCT at 6, 8, and 10 weeks of age, termination was at 26 weeks of age: SA, were sham operated and given SAA negative cells, n=7. SB, were sham operated and given SAA positive cells, n=7. IA, had unilateral renal ischemia for 50 min and given SAA negative cells, n=8. IB, had unilateral renal ischemia for 50 min and given SAA positive cells, n=8. CS, were sham operated PCK rats that did not receive cells, n = 5. CI, were PCK rats subjected to unilateral renal ischemia and did not receive cells. We followed renal function and structure with Dynamic Contrast Enhanced CT (DCE‐CT). Donor cells were found on the cyst walls and damaged tubules. The donor cells were identified 16 weeks post‐transplant by PCR of the SRY (male gene in female kidneys), transferred SAA gene, as well as FISH of the Y chromosome, and by renal genotype revealing mutated (endogenous) and wild type (donor) ARPKD genes. The SAA positive “B” cells drastically improved function and structure and diminished the number of cysts. Transplanted “A” cells also had a positive effect but were less effective than “B” cells. IRCT is an effective means to retard cyst development and progression (all “B” groups significantly different than corresponding “A” groups, p <0.05) in the PCK and has a great potential for PKD therapy.Grant Funding Source: NIH, DoD, VA