Acute renal failure is a frequent clinical problem with an increasing incidence, an unacceptably high mortality rate that has not improved in more than 40 years, and no specific treatment, yet renal failure is not the usual cause of death. The role of inflammation has been documented in both acute renal injury and cardiac dysfunction. Several investigators have shown that congestive heart failure is associated with increased mortality in patients with acute renal failure. This article reviews some of the cardiac and other distant organ effects of acute renal injury that may be important in the morbidity and mortality observed clinically. Cardiac changes after experimental renal ischemia include cytokine induction, leukocyte infiltration, cell death by apoptosis, and impaired function. I propose that the extrarenal effects of kidney injury must be considered in designing therapies. Acute renal failure has systemic consequences and must be thought of as more than a kidney disease.