Renal ischemia-reperfusion injury (IRI) occurs during many procedures and conditions such as renal transplantation and partial nephrectomy and might lead to renal impairment. The efforts to reduce the impact of IRI are ongoing. Dexpramipexole, an orally-bioavailable selective dopaminergic agonist, was found to inhibit inflammation and injury sequelae in different conditions including stroke, chronic neuropathy and myocardial ischemia. However, the effects of dexpramipexole on any form of renal injury has not been investigated yet. Therefore, the aim of this study was to investigate the effects of dexpramipexole in a rat model of bilateral warm renal ischemia-reperfusion injury.

Studies were performed on Wistar rats. Dexpramipexole (0.5 mg/kg) was administrated intraperitoneally twice daily for two days prior to intervention (IRI/sham surgery) and continued for 72 hours post-intervention. G-Sham and G-Sham/Dx (n=10 each) underwent sham surgery whereas G-IRI and G-IRI/Dx (n=10 each) underwent bilateral warm renal ischemia for 35 minutes. G-Sham and G-IRI received the vehicle whereas G-Sham/Dx and G-IRI/Dx received dexpramipexole. Renal functions were assessed 72 hours after ischemia. From previous similar studies in rats, ten animals per group was sufficient demonstrate any significant differences [1, 2].

Dexpramipexole did not affect the basal renal functions. Dexpramipexole significantly attenuated the IRI-induced alterations in serum creatinine (0.34±0.04 vs. 0.64±0.11), serum urea (79.4±6.3 vs.145.6±26.1), creatinine clearance (1.56±0.16 vs. 0.69±0.16) and urinary albumin creatinine ratio (0.12±0.01 vs. 0.18±0.02) when comparing G-IRI/Dx to G-IRI (P<0.05 for all). Dexpramipexole also ameliorated the alterations in markers of renal injury, pro-apoptotic gene, oxidative stress markers and histological changes. For instance, the gene expression of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the G-IRI/Dx and G-IRI were (402.4±51.6 vs.789.5±82.9) and (20.3±1.6 vs. 28.2±3.2), respectively (P<0.05 for both).

Dexpramipexole mitigated the alteration in renal functions, markers of renal injury, pro-apoptotic gene, oxidative stress markers and histological changes caused by renal ischemia-reperfusion injury

Dexpramipexole has a reno-protective effect on the IRI-induced renal dysfunction as it significantly ameliorated the alterations in kidney functions, kidney injury markers, pro-apoptotic gene, oxidative stress markers and the histological changes. These findings could have clinical implications

Hammad, F.T., et al., The Effect of Nerolidol Renal Dysfunction following Ischemia-Reperfusion Injury in the Rat. Nutrients, 2023. 15(2).
Hammad, F.T., et al., Endotelin ETA and ETB receptor antagonism during cold preservation in renal transplantation. Transplantation, 2001. 71(5): p. 619-27.