Renoprotective effect of pulsatile perfusion machine RM3: pathophysiological and kidney injury biomarker characterization in a preclinical model of autotransplanted pig

Abstract

To assess the effect of machine perfusion (MP) on renal function recovery vs kidney preservation in static cold storage (CS), in a large animal preclinical model. To assess whether MP benefits are dependent on the preservation solution used. Using an established autotransplantation pig kidney model associated with a contralateral nephrectomy we studied the impact of MP against the deleterious effects of warm ischaemia (WI; 60 min), then 22 h of cold ischaemia using MP or static CS, followed by autotransplantation. We used Berzer MP solution (MPS), recommended for MP, and Institut Georges Lopez preservation solution (IGL-1), designed for CS. The pigs were divided into four study groups: MPS-CS: static CS with MPS (n = 7); MPS-MP: renal perfusion with MPS using the Waters Medical Systems (Rochester, MN, USA) RM3 pulsatile machine (n = 7); IGL-CS: static CS with IGL-1 solution (n = 7); IGL-MP: renal perfusion with IGL-1 solution (n = 7). The effect of ischaemia was determined using different variables: pig survival; plasma creatinine; proteinuria; oxidative stress; tubular sodium reabsorption rate; and tissue damage at 1 month. Pig survival was higher in MP and IGL groups compared to MPS-CS. Plasma creatinine levels did not differ among the groups, but proteinuria assay showed significant benefits for the MP vs static CS groups. Histological evaluation of kidney grafts showed more injury in the CS groups than in the MP groups. Urinary measurement of tubular enzyme activity differed substantially among the groups, highlighting the benefits of MP in maintaining brush border integrity. In our model reproducing the conditions of deceased after cardiac arrest donors we show that MP decreases the risk of renal dysfunction and preserves kidney parenchyma. A non-invasive urinary enzyme assay can provide valuable information on graft integrity. The preservation solution used is important as the wrong solution can decrease the benefits of MP.