Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats

Abstract

Background: The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury.

Methods: Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured.

Results: Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups.

Conclusions: Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

Keywords: Acute kidney injury; Blood transfusion; Endothelial dysfunction; Microcirculation; Renal oxygenation; Sepsis.

Figures

Fig. 1

Experimental protocol. Time frame of the study. BT blood transfusion, FR fluid resuscitation, LPS lipopolysaccharide, MAP mean arterial pressure

Fig. 2

Renal oxygenation parameters. a Evolution of microvascular oxygen tension in the renal cortex (CμPO2) in the four groups at baseline (T0), T1, T2, and T3. b Renal venous partial pressure of oxygen (PO2) at T3 in the four groups. c Evolution of renal oxygen delivery (DO2ren) in the four groups at T0, T1, T2, and T3. d Renal oxygen consumption (VO2ren) at T3 in the four groups. ##P < 0.01, ###P < 0.001, versus control; *P < 0.05, **P < 0.01, ***P < 0.001, versus LPS; †P <0.05, versus LPS + FR. The values are shown as mean ± SEM. See Fig.1 for definitions of the time points. BT blood transfusion, FR fluid resuscitation, LPS lipopolysaccharide

Fig. 3

Hemoglobin, pH, serum lactate, and liver function during septic shock and resuscitation. a Hemoglobin concentrations at T0, T1, T2, and T3 in the four groups. b pH at T3 in the four groups. c Serum lactate levels at T2 and T3 in the four groups. d Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels at T3 in the four groups. #P < 0.05, ##P < 0.01, versus control; *P < 0.05, **P < 0.01, versus LPS; †††P <0.001, versus LPS + FR. The values are shown as mean ± SEM. See Fig.1 for definitions of the time points. BT blood transfusion, FR fluid resuscitation, LPS lipopolysaccharide

Fig 4

Kidney function and metabolic cost during septic shock and resuscitation. a Serum creatinine (SCr; μmol/l) at T0 and T3 in the four groups. b Creatinine clearance (ml/mn) at T0 and T3 in the four groups. c VO2/TNa+ (oxygen consumption per sodium reabsorbed (metabolic cost)) at T3 in the control group, LPS + FR group and LPS + BT group. #P < 0.05, ##P < 0.01, versus control; *P < 0.05, **P < 0.01, versus LPS; †P <0.05, versus LPS + FR. The values are shown as mean ± SEM. See Fig.1 for definitions of the time points. BT blood transfusion, FR fluid resuscitation, LPS lipopolysaccharide

Fig. 5

Renal histological changes and renal expressions of eNOS and iNOS during septic shock and resuscitation. a Representative periodic acid Schiff staining in the kidneys of the control, LPS, LPS + FR, and LPS + BT rats (original magnification × 400) and tubular injury scores in the four groups. Tubular vacuolization images of the LPS and LPS + FR groups further demonstrate the considerable tubular vacuolization (asterisks) as well as the loss of the brush border in the renal tubule (closed arrows). b Quantification of the tubular injury scores in the kidney sections. c Quantification of endothelial nitric oxide synthase (eNOS) staining intensities (H-score) in the kidney sections. d Quantification of inducible nitric oxide synthase (iNOS) staining intensities (H-score) in the kidney sections. The values are shown as mean ± SEM. ###P < 0.001, versus control; **P < 0.01, versus LPS; †P <0.05, †††P <0.001, versus LPS + FR. BT blood transfusion, FR fluid resuscitation, LPS lipopolysaccharide