Ischaemic Preconditioning attenuates Chronic Renal Damage following Ischaemia Reperfusion Injury

Abstract

ABSTRACTAcute Kidney Injury (AKI) is a common cause of Chronic Kidney Disease (CKD). The leading cause of AKI worldwide is Ischaemia Reperfusion Injury (IRI), seen most commonly in the clinical setting as a result of sepsis-driven hypotension. We are increasingly recognising, however, that AKI and CKD are one closely associated continuum of disease, rather than distinct entities. Ischaemic Preconditioning (IPC) is a strategy aimed at reducing the deleterious effects of IRI. This study demonstrates an efficacious model of kidney IRI, and the protective influence of IPC in attenuating renal injury/fibrosis.A rat model of bilateral kidney IRI was used: Male Lewis rats (n=84) were assigned to IRI, sham or IPC. In IRI, renal pedicles were clamped for 45 minutes. IPC groups underwent pulsatile IPC prior to IRI. Kidneys were retrieved at 24-hours, 48-hours, 7-days, 14-days and 28-days, and assessed histologically.IRI led to marked histological damage and renal fibrosis development by 28 days. Histological injury scores and degree of fibrosis were significantly increased following IRI and attenuated with IPC. IPC resulted in a 66% reduction in renal fibrosis at 28 days (p<0.001). IRI also led to a significant increase in serum creatinine acutely, which was attenuated by IPC (p<0.0001). Interestingly at 14-days, there was limited histological damage and differentiation between IRI and IPC kidneys was difficult.IPC can protect from both acute and chronic kidney damage. 14-days post IRI represents a transitional phase, which maybe a timepoint for commitment to either fibrosis or recovery, and hence offers potential for therapeutic intervention.