A Review of Studies of Perfusion Storage of Pig Kidneys and Their Relevance to Clinical Xenotransplantation.

Abstract

Kidney allotransplantation remains the optimal treatment for end-stage renal disease, but the shortage of donor organs is a persistent issue. Xenotransplantation using gene-edited pig kidneys has shown promise in overcoming this limitation. However, there remain hurdles that include ischemic injury during transportation. The impact of prolonged storage on gene-edited porcine kidneys is not well understood, and few studies have evaluated preservation methods under conditions relevant to xenotransplantation. The present review examines various methods of kidney preservation, focusing on their applicability to xenotransplantation. Methods such as static cold storage (SCS), hypothermic machine perfusion (HMP), and normothermic machine perfusion (NMP) each offer advantages and drawbacks. SCS is widely used but can lead to poor outcomes when kidneys are stored for extended periods. HMP improves renal function and reduces ischemia-reperfusion injury but is limited by its low-temperature metabolic restrictions and benefits from oxygenation. NMP, by maintaining kidneys at physiological temperatures, allows for metabolic activity and real-time viability assessment, though it is associated with logistical challenges. Recent studies suggest that for long periods of storage NMP may better preserve kidney function than HMP. Techniques such as supercooling and partial freezing are in their infancy but offer the prospect of long-term preservation. In summary, long-term storage of pig kidneys could become feasible with advances in machine perfusion or supercooling/cryopreservation techniques. If successful, these innovations would enable the global distribution of gene-edited pig kidneys. However, if meaningful results are to be obtained that are relevant to clinical pig kidney xenotransplantation, future preclinical studies need to be much simpler than those carried out in relation to kidney allotransplantation.