Renal regeneration in diabetic nephropathy

Abstract

Diabetic nephropathy (DN) causes chronic kidney disease (CKD) and end‐stage renal disease (ESRD). We now introduce a method of renal regeneration by infusing cells expressing the tubulogenic protein SAA1. We tested in obese/diabetic Zucker diabetic/SHHF (ZS) rats the hypothesis that CKD can be abrogated by infusions of cells. We studied four groups, diabetic ischemic (subjected to bilateral renal ischemia for 20 min) and transplanted with cells expressing an empty vector (ADI, n = 9), diabetic ischemic transplanted with SAA expressing cells (BDI, n = 9), sham operated diabetic transplanted with SAA negative cells (ADS, n = 6), and diabetic sham transplanted with renal cells expressing SAA (BDS, n = 6). ZS rats were subjected to ischemia or sham surgery at 10 weeks of age, and given two infusions (1.5 × 106 cells per injection) at 15 and 20 weeks of age. The rats were terminated at 34 weeks of age. ADI had severe renal failure with creatinine clearance of 0.8 ± 0.1ml/min, 1.5 ±0.2, in BDI (p = 0.009), and unchanged in ADS 1.5 ± 0.2, and BDS 1.3 ± 0.3. Fractional interstitial fibrosis (IF) was 25 ± 2 % in ADI, 8 ± 1 in BDI (p <0.001). In ADS, IF was 12 ± 1 and 7 ± 1 in BDS, (p<0.01). Microvascular density was lowest in ADI, 7±1, and 16±2 in BDI, (p<0.05), 13±1 in ADS, and 18±1 in BDS (p<0.05). We conclude: infused primary kidney cells regenerate the vasculature and epithelial mass and stop renal decline in progressive CKD due to DN.