The renal transcriptome differs between donors after circulatory death and donors after brain death, which may influence the efficiency of ischemic preconditioning

Background: We have developed two types of rat models to investigate the impact of mesenchymal stromal cells (MSC) in the ischemic preconditioning of kidneys from Donor after Circulatory Death (DCD) and Donor after Brain Death (DBD) Methods: Normal saline (S) or 1.5x106 MSC were injected 6h prior to graft harvesting. In the DCD groups, a 20-min warm ischemia occurred. Kidneys were flushed and directly immersed for 14 hours in IGL1 at 4°C. Serum and urine samples were collected before treatment and at the time of nephrectomy. Renal function was evaluated. Kidney histology was assessed by PAS staining and KIM1 immunostaining. Total RNA was extracted from kidney tissue for RNAseq Results: After 6h of anesthesia or brain death, SCr increased in S- and MSC-treated DBDs, but it was lower in MSC-treated rats (MSC-DBD +6h BD 0.5+-0.2mg/dL vs S-DBD +6h BD 0.7+-0.1mg/dL). Urinary KIM1 was lower in MSC-DBD (S-DBD 10.9±4.56 vs MSC-DBD 7.1±1.7). Acute Tubular Necrosis (ATN) and KIM1 expression were higher in S-DBD (ATN: DBD 65±24 % of surface vs DCD 39±27 % of surface and KIM1: DBD 0.39±0.24 % of surface vs DCD 0.10±0.09 % of surface). RNAseq showed that proinflammatory and proapoptotic pathways were upregulated in DBD, whereas transmembrane transport and metabolic pathways were downregulated, compared to DCD. Conclusions: The RNA profiles of the kidneys are different upon donor types, which may impact the response to MSC-based ischemic preconditioning