Anesth Analg 2008; 106:1593-
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e31816a31ad
LETTER TO THE EDITOR
Section Editor:
Lawrence Saidman
Aprotinin and Urinary Neutrophil Gelatinase-Associated Lipocalin After Cardiac Surgery
Gebhard Wagener, MD, and
H. Thomas Lee, MD, PhD
Department of Anesthesiology; College of Physicians and Surgeons; Columbia University; New York City, New York; gw72{at}columbia.edu
To the Editor:
In a previous study, we detected increased urinary neutrophil gelatinase- associated lipocalin (NGAL) levels in patients undergoing cardiac surgery and anesthesia who eventually developed acute renal dysfunction,1 whereas in a second study, we showed a positive correlation between urinary NGAL and aprotinin.2 We wish, however, to clarify an issue raised by McEvoy et al. who, in a recent review,3 pointed out that NGAL levels in the aprotinin study were lower than in the study correlating urinary NGAL with renal dysfunction after cardiac surgery and anesthesia.
In our initial study,1 we measured urinary NGAL with semiquantitative immunoblotting technique, whereas in the subsequent study regarding the association of urinary NGAL and aprotinin,2 we used a commercially available and more quantitative enzyme-linked immunosorbent assay (ELISA) kit for the detection of NGAL. When measuring the urinary NGAL with both techniques in 396 samples, we found that NGAL levels measured with immunoblotting technique were on average 2.7 times higher than those measured with ELISA. However, there was a strong positive correlation between the two methods. [Spearman r = 0.776; 95% CI = 0.732–0.813; P < 0.0001)]. Unfortunately, ELISA was not commercially available when we were performing the initial study. In our second study, the mean urinary NGAL levels of patients who received aprotinin were approximately the same as the mean urinary NGAL levels of patients who later developed acute renal dysfunction. For example 3 h after cardiopulmonary bypass, mean NGAL in the aprotinin group was 2006 ± 114 ng/mL and in the group with acute renal dysfunction 1640 ± 117 ng/mL (ns).
We would like to also postulate on a possible mechanism of exacerbated renal injury by aprotinin not mentioned in the review by McEvoy et al.3 It is well-known that aprotinin inhibits plasma and tissue kallikrein and kinin cascade in vitro as well as in vivo as McEvoy et al. reference in their review. Several animal studies have shown that kinins and kallikrein system plays a crucial role in protecting the kidney after renal insult including ischemia reperfusion injury.4–6 Inhibition of kinin and kallikrein cascade by aprotinin may reduce the kidney's endogenous protective mechanism and amplify renal injury during cardiopulmonary bypass.
REFERENCES
- Wagener G, Jan M, Kim M, Mori K, Barasch JM, Sladen RN, Lee HT. Association between increases in urinary neutrophil gelatinase-associated lipocalin and acute renal dysfunction after adult cardiac surgery. Anesthesiology 2006;105:485–91[Web of Science][Medline]
- Wagener G, Gubitosa G, Jalbout M, Sladen RN, Lee HT. Aprotinin increases urinary NGAL, a marker for renal tubular injury after cardiac surgery. Anesthesiology 2006;105:A1732–0
- McEvoy MD, Reeves ST, Reves JG, Spinale FG. Aprotinin in cardiac surgery: a review of conventional and novel mechanisms of action. Anesth Analg 2007;105:949–62[Abstract/Free Full Text]
- Bledsoe G, Shen B, Yao Y, Zhang JJ, Chao L, Chao J. Reversal of renal fibrosis, inflammation, and glomerular hypertrophy by kallikrein gene delivery. Hum Gene Ther 2006;17:545–55[Web of Science][Medline]
- Kakoki M, McGarrah RW, Kim HS, Smithies O. Bradykinin B1 and B2 receptors both have protective roles in renal ischemia/reperfusion injury. Proc Natl Acad Sci USA 2007;104:7576–81[Abstract/Free Full Text]
- Zhang JJ, Bledsoe G, Kato K, Chao L, Chao J. Tissue kallikrein attenuates salt-induced renal fibrosis by inhibition of oxidative stress. Kidney Int 2004;66:722–32[Web of Science][Medline]
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