doi: 10.1161/CIRCULATIONAHA.107.742833
(Circulation. 2008;117:e473.)
© 2008 American Heart Association, Inc.
Correspondence |
Letter by Landis et al Regarding Article "Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients"
Edmund Cohen Laboratory for Vascular Research, Chronic Disease Research Centre, University of the West Indies, Bridgetown, Barbados
Cardiac Surgery Unit, Hammersmith Hospital, Imperial College London, London, UK
Division of Cardiothoracic Surgery, Boston University, Boston, Mass
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.
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Acknowledgments |
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Disclosures
All authors have received speaker’s fees from Bayer Pharmaceuticals. Drs Landis and Poston have received a research grant (phase IV) from Bayer Pharmaceuticals.
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References |
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 Top References |
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1. Furnary AP, Wu Y, Hiratzka LF, Grunkemeier GL, Page US 3rd. Aprotinin does not increase the risk of renal failure in cardiac surgery patients. Circulation. 2007; 116 (suppl I): I-127–I-133.[CrossRef][Medline] [Order article via Infotrieve]
2. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006; 354: 353–365.
3. Ferraris VA, Bridges CR, Anderson RP. Aprotinin in cardiac surgery. N Engl J Med. 2006; 354: 1953–1957.
4. Baran D, Tenstad O, Aukland K. Aprotinin uptake in the proximal tubules in the rat kidney: I: length of proximal tubular uptake segment. J Struct Biol. 2003; 142: 402–408.[CrossRef][Medline] [Order article via Infotrieve]
5. Sedrakyan A, Treasure T, Elefteriades J. Effect of aprotinin on clinical outcomes in coronary artery bypass graft surgery: a systematic review and meta-analysis of randomized clinical trials. J Thorac Cardiovasc Surg. 2004; 128: 442–448.
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