Abstract
Background and Aims
Acute kidney injury (AKI) is associated with significant in-hospital morbidity and mortality, particularly in those admitted to the Intensive care units, where mortality rates may exceed 50%. Besides increased mortality rates, there are chronic consequences that carry high risk of developing or exacerbating chronic kidney disease and accelerated development of the end-stage renal disease. Renal ischemia/reperfusion injury is a common cause of AKI and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of combined hyperbaric oxygen (HBO) preconditioning and apocynin treatment on kidney hemodynamics, function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury.
Method
Male SHR were randomly selected in three experimental groups: sham-operated group (SHAM, n=9), AKI control group (AKI, n=11) and AKI group with HBO preconditioning and apocynin treatment (AKI+APO+HBO, n=13). HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes and day before AKI induction. All surgical procedures were performed in anaesthetized rats and AKI was induced by removal of the right kidney and atraumatic clamp occlusion of the left renal artery for 45 minutes. NADPH oxidase inhibitor, apocynin (40 mg/kg b.m., intravenously) was applied as a bolus injection 5 minutes before clamp removal. All hemodynamic parameters were measured 24 hours after reperfusion. After hemodynamic measurements, blood samples were collected and used for further analysis. Animals were sacrificed by pentobarbital overdose injection. Kidney tissue was removed and then prepared for histological examination.
Results
AKI significantly increased renal vascular resistance (RVR, p<0.001) and reduced renal blood flow (RBF, p<0.001), which were significantly improved in group with HBO preconditioning with apocynin treatment (RVR, p<0.05; RBF, p<0,01). AKI induction significantly increased plasma creatinine (p<0.001), urea (p<0.001), phosphate (p<0.001) levels. Remarkable improvement, with decrease in creatinine (p<0.001), urea (p<0.01) and phosphate (p<0.001) levels was observed in treated group. While AKI induction significantly increased plasma KIM – 1 levels (p<0.001), HBO preconditioning with apocynin treatment decreased its levels (p<0.05). Considering renal morphology, in SHAM operated rats, normal morphology of glomeruli, tubulointerstitium, and blood vessels were observed including rare kidney specimens with a few PAS positive casts in the lumen of the tubules. In animals with AKI significant morphological alterations were present: tubular cells necrosis, dilatation of certain segments of the proximal and distal tubules, mostly with loss of brush-border. The most notable changes were present in the cortico-medullary zone, where the broad areas of tubular necrosis and a large number of PAS positive casts in the collecting ducts were observed. In treated animals degrees of morphological changes were significantly lower compared to AKI control. There were reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation.
Conclusion
HBO preconditioning and apocynin treatment improve renal hemodynamics, function and in SHR which suffer AKI. These results suggest that it is reasonable to assume that HBO preconditioning and NADPH oxidase inhibition potentially may have beneficial effects, but further comprehensive experimental and clinical studies are needed to confirm these promising results.
The Impact of High Mobility Group Box 1 Protein (HMGB1) on Renal Ischemia‐Reperfusion Injury in Male and Female Spontaneously Hypertensive Rats (SHR)
