Remote Ischemic Conditioning in a Model of Severe Renal Ischemia–Reperfusion Injury

Abstract

Ischemia-reperfusion (I/R) injury is a leading cause of acute renal dysfunction. Remote ischemic conditioning (rIC) is known to protect organs exposed to I/R. We sought to investigate whether rIC would influence renal function recovery in a severe renal I/R injury rat model. Rats were randomly assigned to four experimental groups following median laparotomy and right nephrectomy: Sham (n = 6); 30-min left renal ischemia (RI) only (n = 20); RI+rIC (n = 20) (four 5-min cycles of limb ischemia interspersed with 5-min limb reperfusion during RI); RI+erythropoietin pre-treatment (EPO) (n = 20). Renal function was evaluated by assessing blood urea nitrogen (BUN) and serum creatinine (Cr) levels before surgery and after 1 day of reperfusion. All animals were monitored for 7 days for survival analysis. BUN and Cr baseline levels did not significantly differ between groups. At Day 1, BUN and Cr were significantly higher than baseline values in all groups. BUN and Cr levels did not significantly differ at Day 1 between RI and RI+rIC (p = 0.68). Conversely, EPO pre-treatment injected 60 minutes before RI was associated with lower BUN and Cr levels compared to RI (p < 0.001 and p = 0.003, respectively) and RI+rIC (p < 0.001 and p = 0.001, respectively). In addition, 7-day survival rates were significantly higher in the Sham group (100%) compared to RI (50%; p = 0.039 vs Sham) and RI+rIC (45%; p = 0.026 vs Sham). Conversely, survival rate did not significantly differ between the Sham and RI+EPO groups (70%, p = 0.15). In conclusion, rIC affected neither acute renal dysfunction nor early mortality in a severe I/R renal injury rat model, contrary to EPO pre-treatment.

Pharmacological prevention of renal ischemia–reperfusion injury in a rat model

“…It can arise from various aetiologies including sepsis, haemorrhage, organ transplantation and shock. 1,2 IRI remains a leading cause of acute kidney injury (AKI) in the setting of renal transplants as it can lead to both acute and chronic graft failure. 3,4 The harmful effects of IRI are twofold.…”

“…17 Non-pharmacological interventions such as remote ischaemic preconditioning have been tested with varying degrees of success in animal models. 2,18 However, there remains a need for the discovery of a therapeutic agent which can be suitable for use in humans. We investigate the efficacy of three different therapeutic agents which could potentially be used in patients with multi-organ IRI.…”

“…Renal ischemia–reperfusion injury (IRI) can cause significant morbidity and mortality. It can arise from various aetiologies including sepsis, haemorrhage, organ transplantation and shock 1,2 . IRI remains a leading cause of acute kidney injury (AKI) in the setting of renal transplants as it can lead to both acute and chronic graft failure 3,4 …”

“…A number of pharmacological agents have been investigated to prevent the effects of renal IRI in animal models such as erythropoietin, 15 allopurinol 16 and hydrogen sulphide 17 . Non‐pharmacological interventions such as remote ischaemic preconditioning have been tested with varying degrees of success in animal models 2,18 . However, there remains a need for the discovery of a therapeutic agent which can be suitable for use in humans.…”