Evidence-Based Renal Protection in Cardiac Surgery

Abstract

Acute renal dysfunction is a common serious complication of cardiac surgery. Although a diversity of mechanisms exist by which the kidney can be damaged during cardiac surgery, atheroembolism, ischemia-reperfusion, and inflammation are believed to be primary contributors to perioperative renal insult. In addition, the high metabolic demands of active tubular reabsorption and the oxygen diffusion shunt characteristic of renal circulation make the kidney particularly vulnerable to ischemic injury. Remote effects of acute renal injury likely contribute to the strong association of this condition with other major postoperative morbidities and mortality and justify the search for renoprotective agents, even when dialysis is never required. Nonpharmacologic preventive strategies include procedure planning that is based on risk stratification, avoidance of nephrotoxins, and meticulous perioperative clinical care, including optimizing intravascular volume and attention to modifiable risk factors such as minimizing hemodilution. Although numerous pharmacologic interventions to prevent or treat acute renal injury have shown promise in animal models, randomized placebo-controlled clinical trials that have looked at measures of significant adverse outcomes such as death and dialysis have not confirmed a benefit.

Effects of N-acetylcysteine and pentoxifylline on remote lung injury in a rat model of hind-limb ischemia/reperfusion injury

“…Pentoxifylline acts by increasing intracellular cyclic adenosine monophosphate on red blood cells, thus improving oxygen delivery to ischemic tissues, increasing cyclic adenosine monophosphate on polymorphonuclear leukocytes, and decreasing oxygen free radical production. ( 30 - 33 ) Recent reports suggest that pentoxifylline can enhance the chemotactic response of neutrophils, as well as inhibiting phagocytosis and superoxide production by neutrophils and monocytes. ( 34 ) Those findings have translated into clinical benefits, pentoxifylline having been used in order to attenuate I/R injury in patients with lung, intestinal, or kidney damage.…”

The effects of pentoxifylline into the kidneys of rats in a model of unilateral hindlimb ischemia/reperfusion injury

“…Although histological evidence of injury was demonstrated only in the lung, the biochemical evidence of simultaneous hepatic and renal dysfunction indicates that multiple organ dysfunctions following hindlimb ischemia reperfusion occur as a central systemic event rather than sequential failure of individual organs 4,5,6 . Multiple pharmacological agents could potentially limit reperfusion injury, including substances that target free radicals, limit initiation of the inflammatory response, or serve as substrate for compounds that preserve endothelial function 7 . Pentoxifylline (PTX) is a methylxanthine derivative with multiple hemorheologic properties.…”

“…Pentoxifylline (PTX) is a methylxanthine derivative with multiple hemorheologic properties. PTX through effects of increasing intracellular cyclic AMP on red blood cells improve the oxygen delivery to ischemic tissues and also increases the AMP cyclic on PMN and decreased oxygen free radical production [7][8][9][10][11] . In addition, PTX limited the inflammatory response with reduction in cellular activation, phagocytosis and endothelium adhesion.…”

Evaluation of cystatin C with iohexol clearance in cardiac surgery

“…R enal dysfunction after cardiac surgery is not unusual, with 1–5% of the patients requiring dialysis 1,2 . It causes discomfort for the patients and generates an additional cost for the healthcare system.…”