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To review the current literature on possible mechanisms by which mechanical ventilation may initiate or aggravate acute renal failure.A Medline database and references from identified articles were used to perform a literature search relating to mechanical ventilation and acute renal failure.Acute renal failure may be initiated or aggravated by mechanical ventilation through three different mechanisms. First, strategies such as permissive hypercapnia or permissive hypoxemia may compromise renal blood flow. Second, through effects on cardiac output, mechanical ventilation affects systemic and renal hemodynamics. Third, mechanical ventilation may cause biotrauma—a pulmonary inflammatory reaction that may generate systemic release of inflammatory mediators. The harmful effects of mechanical ventilation may become more significant when a comorbidity is present. In these situations, it is more difficult to maintain normal gas exchange, and moderate arterial hypoxemia and hypercapnia are often accepted. Renal blood flow is compromised due to a decreased cardiac output as a consequence of high intrathoracic pressures. Furthermore, the effects of biotrauma are not limited to the lungs but may lead to a systemic inflammatory reaction.The development of acute renal failure during mechanical ventilation likely represents a multifactorial process that may become more important in the presence of comorbidities. Development of optimal interventional strategies requires an understanding of physiologic principles and greater insight into the precise molecular and cellular mechanisms that may also play a role.