Cellular adaptive changes in AKI: mitigating renal hypoxic injury

Hypoxia plays a role in ischemic, toxic and sepsis-induced acute kidney injury. Evolving hypoxia triggers renal adaptive responses that may mitigate the insult, leading to sublethal forms of cell injury. The unique capability of the kidney to downregulate oxygen consumption for tubular transport could represent one such adaptive response which promotes maintenance of renal oxygenation, thereby preserving cellular integrity. Tran et al. recently explored a novel mechanism that might prevent tubular damage by downregulation of mitochondrial biogenesis and oxygen consumption. Using expression profiling of kidney RNA in endotoxemic rodents and complementary studies in vitro and in PGC-1α knockout mice, they found a sepsis-related decline in PPARγ coactivator-1α (PGC-1α) expression and of PGC-1α-dependent genes involved in oxidative phosphorylation. This response may explain their observation of a paradoxical preservation of kidney oxygenation and structural integrity in sepsis, despite reduced renal blood flow and oxygen delivery. Thus, resetting of mitochondrial respiration and oxygen consumption during sepsis might be added to the growing list of adaptive responses that occur during hypoxic stress. This review will focus on these mechanisms that mitigate evolving hypoxic injury, even at the expense of transient renal dysfunction.