The Domestic Pig as a Translational Model of Hyperoxaluria: Application to the Study of Oxalate-Dependent Renal Dysfunction

The purpose of this pilot study was to develop and characterize an in vivo porcine model of oxalate-induced renal injury using intravenous infusion of sodium oxalate (NaOx). 2 experimental regimens were developed to replicate acute and chronic hyperoxaluria. In the acute model, 3 different doses of 1% NaOx were administered over 15 hours, resulting in a dose-dependent increase in plasma oxalate concentration (Cmax: 42.4-122.4 µM) and transient hyperoxaluria, with a return to baseline values 6-8 hours after stopping the infusion of NaOx solution. In the chronic model, repeated infusions of NaOx for 7-11 days led to persistent hyperoxalemia (up to 302.4 µM), decreased appetite and increasing renal failure. Histological analysis revealed dose-dependent calcium oxalate (CaOx) deposits in renal tissue (1.85%-9.55% of renal surface area), consistent with moderate to severe nephrocalcinosis. The model represents the key clinical features of both acute kidney injury and the progressive nephrocalcinosis observed in primary hyperoxaluria and oxalaturia. Due to the physiological similarity between pigs and humans, the proposed porcine model is valuable for studying the pathophysiology of oxalate excess and for testing the efficacy of new therapies to counteract its toxicity.