Initial experience: ex-vivo perfused pig kidney to study urinary oxalate excretion

Existing animal models of renal oxalate excretion utilize either gut or peritoneal cavity for oxalate absorption. Ex vivo renal perfusion is an established tool for graft preservation. We sought to repurpose this concept to study the early pathogenesis of urinary lithiasis. Juvenile female Yorkshire porcine kidneys were removed laparoscopically and placed on an ex vivo cardiopulmonary bypass circuit utilizing whole-blood based perfusate. Pre-defined goals were identified for each attempt (n = 5) with plans to increase physiologic model complexity. Tissue perfusion and oxygenation were monitored by serial perfusate iSTAT testing. Once steady urine production was achieved, aqueous oxalate was injected into the perfusate. Renal outcomes were assessed by histology and blood/urinary assays. After demonstrating proof-of-concept in early trials, normothermic (37 °C) ex vivo whole-blood perfusion with Steen Solution™ was performed exceeding three hours at physiologic mean arterial pressures. Circuit parameters remained in the physiologic range for electrolytes, temperature, mean arterial pressure, lactate, and pH. Urine was produced in three experiments. Urinary filtrate demonstrated consistently higher urine creatinine compared to perfusate, and arterial perfusate oxalate boluses lead to urinary oxalate spikes followed by continuous oxalate clearance. Histopathologic analysis with H&E and Pizzolato's method staining demonstrated formation of calcium oxalate crystals. In light of these promising metabolite clearances, ex vivo porcine renal perfusion appears to be a feasible alternative to study oxalate excretion. Longer validation studies are necessary to establish this technique as a model for kidney stone pathogenesis.