Cell therapy: intravenous renal cell transplantation for acute and chronic renal failure

Abstract

Acute kidney injury (AKI), chronic kidney disease (CKD) and end‐stage renal disease (ESRD) are major health problems that lack good solutions. We tested the hypothesis that kidney cells from one donor male rat given iv, could regenerate female rat kidneys with AKI or CKD. Isolated rat renal tubules were transfected with empty vector (A) or with SAA cDNA encoding tubulogenic serum amyloid A1 protein (B) and grown. Kidney cells were infused to rats with severe AKI from 50 min of bilateral renal ischemia or CKD from 3 cisplatin injections. Serum creatinine was 3.9 ± 0.7 in A rats and 1.0 ± in B rats after 48 hr. post‐ischemia (mg/dl, mean ± SE, p ≤ 0.05), and renal inflammation and fibrosis were significantly improved. Donor cell engraftment was documented up to 30 days in recipient kidneys. CKD was induced by cisplatin (1.5 mg/Kg), and 3 weeks later rats were infused with either A cells (7 rats) or B cells (7 rats). Twelve days later blood urea nitrogen (BUN) was 101 ± 4 in A rats and 38 ± 18 in B rats (mg/dl, p ≤ 0.05). Renal fibrosis and tubular atrophy was improved in B rats. We also removed one kidney of 6 rats with cisplatin CKD, and auto‐transplanted these cells iv with correction of BUN after 12 days: 53 ± 5 (n = 6 p ≤0.05). We conclude that renal cell transplantation with kidney primary cells restores function and structure in AKI and CKD.