Furosemide exacerbated the impairment of renal function, oxygenation and medullary damage in a rat model of renal ischemia/reperfusion induced AKI.

Abstract Background: Perioperative Acute Kidney Injury (AKI) caused by Ischemia-Reperfusion (IR) is a significant contributor to mortality and morbidity after major surgery. Furosemide is commonly used in postoperative patients to promote diuresis and reduce tissue edema. However, its effects on renal microcirculation, oxygenation and function after AKI are poorly understood. Herein, we investigated the effects of furosemide in rats subjected to IR insult. Methods: 24 Wistar albino rats were divided into 4 groups, with 6 in each; Sham-operated Control (C), Control + Furosemide (C+F), ischemia/reperfusion (IR), and IR+F. After induction of anaesthesia (BL), supra-aortic occlusion was applied to IR and IR+F groups for 45 minutes followed by ongoing reperfusion for 15 minutes (T1) and 2 hours(T2). Furosemide infusion was initiated simultaneously in the intervention groups after ischemia. Renal blood flow (RBF), vascular resistance (RVR), oxygen delivery (DO2ren) and consumption (VO2ren), sodium reabsorption (TNa+), oxygen utilization efficiency (VO2/TNa+), cortical (CμO2) and medullar (MμO2) microvascular oxygen pressures, urine output (UO) and creatinine clearance (Ccr) were measured. Biomarkers of inflammation, oxidative and nitrosative stress were measured and kidneys were harvested for histological analysis. Results: IR significantly decreased RBF, mainly by increasing RVR, which was exacerbated in the IR+F group at T2 (2198 vs 4223 dyne/s/cm5, p<0.05). CμO2 (61.65±6.8 vs 86.02±6.67 mmHg) and MμO2 (51.18±4.16 vs 68.79±4.98 mmHg, p<0.05) were both reduced after IR and did not improve by Furosemide. Moreover, VO2/TNa+ deteriorated in the IR+F compared to IR (78,5±63% vs IR+F:422,5±707% compared to BL values, p=0,07) suggesting a possible harm. Ccr did not change and plasma creatinine increased significantly in IR+F. Histopathology revealed widespread damage both in the cortex and medulla in IR+F and C+F groups. Conclusion: Renal oxygen delivery, medullar and cortical oxygenation and oxygen utilization all declined by furosemide administration after IR insult. Our study suggests that furosemide may cause additional structural and functional impairment to the kidney following ischemic injury and should be used with caution.