Introduction: Despite major advances in renal replacement therapy acute kidney injury (AKI) is still associated with high morbidity and mortality. Beside risk factors like mechanical ventilation, acidosis has been identified as one factor contributing to AKI. However, in critically ill patients with multiple risk factors a differentiated analysis of the influence of acidosis is hard to perform. Therefore, the aim of our study was to evaluate the impact of an acidaemia on renal function excluding sepsis or other infections. Methods: 35 young and healthy pigs were randomized into 6 groups. Three test pairs were settled with or without exposition to a continuos veno-venous haemofiltration (CVVH), respectively. The groups differed by: normoxaemia-balanced acid-base- status (NB-CVVH and NB-CTRL), normoxaemia-acidaemic (NA-CVVH and NA-CTRL) and hypoxaemia-acidaemic (HA-CVVH and HA-CTRL). Due to low-tidal-volume- ventilation and acid-infusion a mixed acidaemia (pH 7.19-7.24) was induced into acidaemic groups. HA-groups underwent an additional hypoxaemia. Acidemia and hypoxaemia were maintained for five hours. Haemodynamics, ventilation parameter, blood gas analysis and diuresis were monitored constantly as well as interleukin-6 (IL-6), TNF-aplha and interleukin-18 (IL-18) in blood and tissue samples, neutrophil gelatinase-associated lipocalin (NGAL) was analyzed in urine specimen. Tissue samples of the kidneys were (immuno-) histologically examined. Results: All animals were haemodynamically stable throughout the entire experiment. Animals had sufficient diuresis facing a physiologic cardiac output at any time. Interestingly, diuresis increased in acidemia groups while urine-pH decreased. Increased plasma levels of IL-18 and NGAL indicated a developing AKI in the acidaemia groups. Concordantly, normoxic- acidaemia groups had significantly more reversible and irreversible cell damage in histopathological examination, just exceeded by hypoxaemia- acidaemia groups. Due to measurements of proinflammatory cytokines in tissue and plasma a biotrauma induced AKI was excluded, because subgroup analysis of immunohistology revealed an inverse correlation between tissue levels of proinflammatory cytokines and histopathological cell damage. Conclusion: We were able to demonstrate that an isolated acidaemia without concomitant sepsis already leads to a relevant histologically detectable damage of the kidneys after only five hours exposition to acidaemia. Immunohistochemical investigations showed that other than inflammatory factors induced the renal damage. Results are leading to the hypothesis that the acidaemia works as a kind of „first hit“ by increasing renal workload with respect to the correction of acid-base-status abnormalities and thereby contributing to a depletion of renal energy reserves. Initially increasing diuresis clinically masks the early onset of an AKI due to the compensation for acidosis by the kidneys. Advisors/Committee Members: [email protected] (contact), m (gender), N.N. (firstReferee), N.N. (furtherReferee).