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Letter by Landis et al Regarding Article “Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients”

Landis, R.C., Taylor, K.M., and Poston, R.S.

Clive Landis






Cardiopulomonary bypass

To the Editor: We read with interest the article by Furnary and colleagues1 showing that aprotinin does not increase the risk of renal failure in cardiac surgery patients, casting further doubt on the conclusions of a study by Mangano et al.2 The article by Furnary et al demonstrates that risk for kidney failure is solely attributed to the greater numerical need for packed red blood cell transfusion in high-risk patients selected by physicians to receive aprotinin, and that packed red blood cells carry with them a highly significant independent risk of causing renal failure. These conclusions echo the concerns expressed in the aftermath of the article by Mangano et al,3 that such an important confounding factor had not been corrected for in multivariate analysis. On the other hand, it is important to discriminate between renal failure and renal insufficiency in the early postoperative period, which does appear to increase in patients receiving aprotinin. Through the use of radiolabeled aprotinin, it has been illustrated that this drug is actively reabsorbed in the proximal convoluted tubule.4 The resulting aprotinin deposits are thought to saturate mechanisms responsible for creatinine reabsorption, thereby leading to a transient change in creatinine clearance. Physicians noticing a rise in creatinine in the postoperative period might be tempted to conclude that aprotinin increases the risk for renal failure. However, clinical data from randomized trials,5 animal models,4 and now the study by Furnary et al,1 are all quite clear in demonstrating a return to normal renal function and no long-term risk of renal failure or dialysis following aprotinin use. In conclusion, we commend Furnary and colleagues for introducing hard new evidence to the issue of aprotinin safety in an article distinguished by the quality of its science, clarity of methodology, and completeness of the clinical dataset.


Lippincott Williams & Wilkins for the American Heart Association