Endocrine Abstracts

Background: Acute kidney injury (AKI) is common and serious, with no specific treatment. AKI may increase the risk of dysfunction in organs other than the kidney, further increasing the morbidity associated with AKI. The mechanisms of organ cross-talk after AKI are unclear. Small animal models have suggested that infiltration of inflammatory cytokines into extra-renal organs leads to cellular extravasation, oedema and further injury. In this study we used a large animal model to investigate the remote organ effects of AKI.

Design: We used an established porcine model of warm ischaemia–reperfusion induced AKI (control, n=12 and AKI, n=17). We assessed remote organ (liver, lung, and brain) effects at 48 h after ischaemia–reperfusion injury. Leukocyte infiltration and apoptosis were assessed using immunofluorescence; cytokines were measured using a cytokine multiplex array. A clinical chemistry analyser measured liver enzymes and gene expression for inflammatory markers was determined by qPCR.

Results: There were no indications of remote organ histopathology or oedema at 48 h after AKI. The number of TUNEL⁺ apoptotic cells varied between organs but was not affected by AKI, and gene expression of caspase-3 was unaffected. There was no evidence of increased leukocyte infiltration at 48 h in the AKI group. Cytokine concentrations in liver and lung lysate, and gene expression of TNF-α or TGFβ1 were not different between groups. However, animals with AKI had a significantly greater increment in enzymes associated with liver injury (AST, ALT, and ALP) relative to controls that lasted for 24 h but returned to baseline by 48 h.

Conclusions: In our large animal model of AKI, in contrast to small animal models, there was little evidence of any remote organ effects. The greater increment in liver enzymes in animals with AKI is an interesting example of hepato-renal cross-talk but is unlikely to represent acute liver injury.