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Ann Thorac Surg 2006;82:1575
© 2006 The Society of Thoracic Surgeons

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Correspondence

Does the Combination of Aprotinin and Angiotensin-Converting Enzyme Inhibitor Cause Renal Failure After Cardiac Surgery?

Anesthesia and Critical Care, Royal Brompton and Harefield NHS Trust, Harefield Hospital, Middlesex UB9 6JH United Kingdom

(Email: d.royston{at}rbht.nhs.uk).

To the Editor:

Dr Royston discloses a financial relationship with Bayer HealthCare, GSK, Organon.

 

I would like to comment on the article by Kincaid and colleagues [1] suggesting an adverse interaction between aprotinin and inhibitors of angiotensin-converting enzyme inhibitor (ACEI).

First, the authors claim a "plausible mechanism" for their observations is induced by vasoconstriction of the efferent glomerular artery. A source reference is not cited. Studies thus far fail to show an effect of aprotinin on angiotensin-stimulated afferent or efferent artery tone [2], or additional effects of aprotinin on renal tubular function after heart surgery [3].

Second, one of three referenced articles suggesting potential nephrotoxic action of aprotinin (reference 7 [1]) showed that creatinine clearance increased from 110.7, to 122.0 and finally 132.9 mL/minute with increasing doses of aprotinin making a direct nephrotoxic effect unlikely.

Third, we have also been interested in interactions between ACEI administration and aprotinin therapy [4]. Of 1,870 patients in our analysis, 381 (20.4%) were taking ACEI until surgery. Biochemical renal impairment was recorded in 6.9% patients allocated to high-dose aprotinin and 6.7% to a placebo. Two other studies from hospitals in which aprotinin was not routinely used showed renal impairment in 7.7% [5] and 7.74% of patients [6]. The Kincaid and colleagues' [1] data showed renal impairment in 1.9% of patients not receiving aprotinin. Compared with our own report [4] and those of others [5, 6], the remarkably low incidence of renal impairment in the nonaprotinin group reported by Kincaid and colleagues' [1] raises the issue of whether risk factors for adverse outcome were similar between aprotinin and nonaprotinin groups. In particular, the authors show a very strong relationship between incidence of renal impairment and blood transfusions (Fig 2 [1]). Figures 3 and 4 [1] suggest some patients received up to 8 units of red cells in addition to aprotinin, a rare scenario for this patient population.

Finally, the authors may agree that the causal relationship suggested in the title, and the conclusion that a combination of ACEIs and aprotinin should be avoided, is somewhat overstated. The article shows administration of a blood transfusion was numerically more important than ACEI and aprotinin combination. Construction of relationships (eg, Fig 3 [1]) using the data of 13 patients (approximately 1% of the study population) may be mathematically sound, but clinically misleading, until more data is forthcoming.

	References

Top References

 

1. Kincaid EH, Ashburn DA, Hoyle JR, Reichert MG, Hammon JW, Kon ND. Does the combination of aprotinin and angiotensin-converting-enzyme inhibitor cause renal failure after cardiac surgery? Ann Thorac Surg 2005;80:1388-1393.[Abstract/Free Full Text]
2. Marchetti J, Helou CM, Chollet C, et al. ACE and non-ACE mediated effect of angiotensin I on intracellular calcium mobilization in rat glomerular arterioles Am J Physiol 2003;284:H1933-H1941.
3. Fauli A, Gomar C, Campistol JM, et al. Kidney-specific proteins in patients receiving aprotinin at high- and low-dose regimens during coronary artery bypass graft with cardiopulmonary bypass Eur J Anaesthesiol 2005;22:666-671.[Medline]
4. Royston D, Spiess B, Levy J, et al. Abnormal rise in plasma creatinine is not associated with administration of high dose aprotinin in patients taking inhibitors of angiotensin converting enzyme having isolated valve or CABG Anesthesiology 2005;103:A413.
5. Mangano CM, Diamondstone LS, Ramsay JG, et al. Renal dysfunction after myocardial revascularization: risk factors, adverse outcomes, and hospital resource utilization Ann Intern Med 1998;128:194-203.[Abstract/Free Full Text]
6. Conlon PJ, Stafford-Smith M, White WD, et al. Acute renal failure following cardiac surgery Nephrol Dial Transplant 1999;14:1158-1162.[Abstract/Free Full Text]

This article has been cited by other articles:

				E. H. Kincaid, N. D. Kon, and J. W. Hammon Reply. Ann. Thorac. Surg., October 1, 2006; 82(4): 1575 - 1576. [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): David Royston Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Royston, D. Search for Related Content PubMed PubMed Citation Articles by Royston, D. Related Collections Extracorporeal circulation