Ann Thorac Surg 2010;89:694-695. doi:10.1016/j.athoracsur.2009.11.050
© 2010 The Society of Thoracic Surgeons
Original Articles: Adult Cardiac
Invited Commentary
Mark Stafford-Smith, MD, FRCPC
Department of Anesthesiology, Duke University Medical Center, Box 3094 DUMC, Durham, NC 27710
(Email: staff002{at}mc.duke.edu).
The race is on to identify, beyond serum creatinine, one or more ideal early biomarkers for acute kidney injury (AKI). Few or no equivalents to creatine kinase MB, troponin, and the ST segment for the heart exist for the kidney. Many believe that the lack of tools to quickly diagnose AKI or monitor renal angina must take partial blame for the frustratingly slow development of renoprotective therapies relative to cardioprotective therapies. Much like acute myocardial infarction, AKI is now being viewed as a threshold diagnosis whose treatment paradigm demands prompt intervention.
Ristikankare and colleagues [1] evaluated cystatin C as a candidate for early AKI recognition and found it no better than serum creatinine in elderly postoperative cardiac surgical patients. As reviewed by these authors, with a few notable exceptions, the emerging consensus on cystatin C from perioperative and critical care studies is consistent with these findings. Why cystatin C struggles to improve on creatinine as an early biomarker may relate to similarities in the mechanism by which the two substances reflect AKI. Like creatinine, circulating levels of cystatin C reflect a balance between its steady production in peripheral tissues and clearance through the kidneys. Decreased clearance with AKI causes creatinine and cystatin C to accumulate to diagnostic levels. In both cases, however, perioperative signal-to-noise confounders, such as hemodilution, disrupt steady state assumptions and complicate AKI recognition.
Other rivals exist in the AKI biomarker race, with many candidates heralding renal insult through mechanisms that are fundamentally different from creatinine accumulation. For example, leakage of damaged renal cellular contents directly into urine underpins tubular enzymuria, including β-N-acetyl-β-d-glucosaminidase and at least eight other biomarker candidates. Another novel group, including some frontrunners, manifest renal injury through markers of the kidney's stress response. These include neutrophil gelatinase-associated lipocalin, urinary interleukin-18, and at least three other candidates. Monitoring of urinary oxygen tension is another method to predict subsequent AKI in cardiac surgical patients.
Some competitors in the AKI early biomarker race are poorly suited specifically to cardiac surgical patients. So called tubular proteinuria biomarkers, including urine 
1- and β2-microglobulin and at least 12 other candidates, reflect AKI through impaired reuptake of small filtered proteins by the kidney, manifesting as spillage into the urine. Notably, because antifibrinolytics such as 
-aminocaproic acid and tranexamic acid selectively block tubule receptors, causing this same proteinuria with apparent benign consequences, these biomarkers are of little value in most cardiac surgical settings.
As we look forward to completion of the several large prospective observational studies currently underway that should help identify the winner(s) of the early AKI biomarker race, it will be important for surgical and anesthesia advocates to highlight AKI biomarker issues unique to cardiac surgery lest these be overlooked in the broader pursuit of consensus AKI definitions.
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References
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- Ristikankare A, Pöyhiä R, Kuitunen A, et al. Serum cystatin C in elderly cardiac surgery patients Ann Thorac Surg 2010;89:689-695.[Abstract/Free Full Text]
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