The inflammatory response in blood and in remote organs following acute kidney injury

Abstract

In patients with acute kidney injury (AKI) mortality remains high, despite the fact that the patients are treated with continuous renal replacement therapy. The interaction between the kidney and the immune system might explain the high mortality observed in AKI. In order to elucidate the interaction between the kidney and immune system we developed a two-hit model of AKI and endotoxemia. Our hypothesis was that ischemia/reperfusion (I/R) of the kidney simultaneously with endotoxemia would generate a more extensive inflammatory response compared to I/R of the hind legs. Our expectation was that elevated levels of cytokines would be found in both blood and in organs distant to the kidneys. Forty mice were divided into five groups. The mice were subjected to the following operations: A: Sham only, no lipopolysaccharide (LPS); B: I/R of both kidneys + LPS; C: LPS only; D: Nephrectomy + LPS; E: I/R of both hind legs + LPS. In groups B and E, I/R times were identical. All mice were kept alive for 24 h and then sacrificed. Levels of interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-α were measured in the blood. The activity of myeloperoxidase (MPO) in lungs, kidneys, and liver was evaluated as an indirect measurement of accumulation of granulocytes. In this study, significantly higher amount of IL-6 and IL-10 in the plasma was observed following renal I/R compared to hind leg I/R. The elevated levels of cytokine in plasma were observed following nephrectomy and endotoxemia. The neutrophil infiltration of distant organs measured by the levels of MPO in the lung and liver also showed a significantly higher level in renal I/R compared to hind leg I/R. Renal I/R is associated with a more pronounced inflammatory response in blood and distant organs. The high cytokine levels measured following nephrectomy might be explained by compromised elimination of cytokines by the kidney in AKI.

A histological study on the effect of pentoxifylline on acute lung injury induced by renal ischemia–reperfusion

“…In addition, mononuclear cellular infiltration including macrophages, neutrophils, and lymphocytes was widely detected. They concluded that, as neutrophils increased in number and infiltrated the lung tissue, lung IRI increased [19]. This was in accordance with the findings of previous studies [15,17].…”

Interleukin-6 and interleukin-10 as acute kidney injury biomarkers in pediatric cardiac surgery

“…Studies in children and adults have demonstrated that these cytokines may be potential biomarkers of AKI [9-12]. It also has been demonstrated in animal models that AKI itself, not just the pro-inflammatory state of sepsis or CPB, induces higher IL-6 and IL-10 levels [13, 14]. …”

Most Important Cellular Changes Involved in Renal Ischemia Reperfusion Injury and the Consequent Impact on Selected Remote Organs

“…Brøchneret et al compared 5 mice (C57BL/6) groups with different subtypes of AKI. This study revealed that Myeloperoxydase production in the lung significantly increased in the groups with acute kidney injury than in limb ischemia and sham groups 82 . Additionally, interleukin (IL)-6 and IL-10 blood levels significantly increased in the AKI groups compared to sham group, suggesting the role of ischemia reperfusion to the systemic inflammatory response.…”