Mitochondrial Dysfunction in Cardiorenal Syndrome.

SIGNIFICANCE

Acute kidney injury (AKI) has a significant impact on the outcomes of critically ill patients, although no effective and specific treatment against AKI is currently available in the clinical setting. It is assumed that reactive oxygen species production by the mitochondria plays a crucial role in renal damage especially caused by cellular apoptosis. Mitochondrial injury in the heart is reported as an important determinant of myocardial contractility. Clinical epidemiological data indicate that remote organ effects induced by AKI, especially organ cross talk between the kidney and heart, might contribute to the poor outcome of AKI patients.

RECENT ADVANCES

Cardiorenal syndrome (CRS) has recently been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these two organs have been suggested; however, the precise mechanisms are still unclarified. Mitochondrial injury in the kidney and heart has been shown as a crucial pathway of AKI and acute heart failure by several animal studies.

CRITICAL ISSUES

Clinical evidence clearly shows cardiorenal interactions in clinically ill patients, but evidence for distant organ effects of AKI on the heart is lacking. We recently found dysregulation of mitochondrial dynamics caused by increased Drp1 expression and cellular apoptosis of the heart in an experimental AKI animal model of renal ischemia-reperfusion.

FUTURE DIRECTIONS

Precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclarified. A recently suggested concept of mitochondrial hormesis may need to be considered in chronic cardiorenal interaction. Identifying the role of mitochondrial injury for CRS will enable the development of novel interventional approaches to reduce mortality associated with AKI. Antioxid. Redox Signal. 25, 200-207.