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(Circulation. 2008;117:e475.)
© 2008 American Heart Association, Inc.

Correspondence

Letter by Bouchard et al Regarding Article "Aprotinin Does Not Increase the Risk of Renal Failure in Cardiac Surgery Patients"

Josée Bouchard, MD; Roy Mathew, MD; Ravindra L. Mehta, MD, DM

Department of Nephrology, University of California San Diego, San Diego, Calif

To the Editor:

Two recent publications have given rise to concerns regarding the safety of intraoperative aprotinin on renal function after cardiac surgery.^1,2 Contrary to these studies, Furnary et al³ demonstrated that aprotinin does not increase the risk of acute renal failure (ARF) independently of the number of transfusions administered. We have 3 concerns regarding the findings of these studies that impair an adequate comparison of their results.

First, all 3 studies used different definitions for ARF. Furnary et al³ selected the new requirement of dialysis as the ARF outcome, presumably because the risk predictive score has been validated for ARF requiring dialysis after cardiac surgery. In comparison, Mangano et al¹ and Karkouti et al² included both dialysis- and nondialysis-requiring ARF in their outcome analysis. Moreover, they set different minimum threshold creatinine values (Mangano et al, 177 µmol/L [2 mg/dL]; Karkouti et al, 100 to 110 µmol/L [1.1 to 1.2 mg/dL]) and either a minimal absolute or percentage of increase from baseline (Mangano et al, 62 µmol/L [0.7 mg/dL]; Karkouti et al, 50%) in defining nondialysis–requiring ARF. As a result, all 3 populations are different and their outcomes cannot be compared.

Second, because intercurrent events after surgery, for example, radiocontrast and nephrotoxic antibiotics, can all contribute to ARF risk, the time between exposure and outcome needs to be prospectively defined. Karkouti et al² limited the time period of analysis to 7 days after surgery, whereas the time period is not clear in the other 2 studies. Consequently, these studies could have included more ARF events unrelated to intraoperative events.

Third, the importance of chronic kidney disease as a risk factor for ARF needs to be considered. Mangano et al¹ and Karkouti et al² demonstrated that chronic kidney disease patients had a higher risk of acute renal dysfunction with the use of aprotinin. Over 30% of patients included in the analysis by Furnary et al³ had elevated baseline creatinine 106 µmol per liter (1.2 mg/dL); however, it is unclear if these patients had a higher incidence of ARF.

These findings emphasize the importance of a standardized definition of ARF in research. The Acute Kidney Injury Network (AKIN) has proposed a new definition and classification with the goal of improving outcomes from ARF.⁴ Recent studies have found that even minor short-term changes in serum creatinine (ie, 0.3 mg/dL or 26 µmol/L) are linked to increased morbidity and mortality.⁵ Thus, acute kidney injury is defined as an absolute increase in serum creatinine of 26 µmol/L, a 1.5-fold increase in serum creatinine from baseline or oliguria defined as urine output less than 0.5 mL · kg^–1 · h^–1 for at least 6 hours within 48 hours. This definition is currently being validated in several settings, including after cardiac surgery, and we would propose that it could permit comparisons across different studies and settings. We look forward to new analyses from Furnary et al considering (1) definitions of acute renal dysfunction by Mangano et al and Karkouti et al, (2) AKIN definition of acute kidney injury, and (3) chronic kidney disease as a risk factor for acute kidney injury.

	Acknowledgments

 
Disclosures

None.

	References

Top References

 

1. Mangano DT, Tudor IC, Dietzel C. The risk associated with aprotinin in cardiac surgery. N Engl J Med. 2006; 354: 353–365.[Abstract/Free Full Text]
   
2. Karkouti K, Beattie WS, Dattilo KM, McCluskey SA, Ghannam M, Hamdy A, Wijeysundera DN, Fedorko L, Yau TM. A propensity score case-control comparison of aprotinin and tranexamic acid in high-transfusion-risk cardiac surgery. Transfusion. 2006; 46: 327–338.[CrossRef][Medline] [Order article via Infotrieve]
   
3. 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]
   
4. Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A. Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007; 11: R31.[CrossRef][Medline] [Order article via Infotrieve]
   
5. Lassnigg A, Schmidlin D, Mouhieddine M, Bachmann LM, Druml W, Bauer P, Hiesmayr M. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol. 2004; 15: 1597–1605.[Abstract/Free Full Text]
   

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