Markers of Kidney Failure During Bypass

In a new study, researchers report the discovery of a series of early biomarkers that may dramatically reduce from three days to two hours the time needed to identify the first signs of potential kidney failure in patients undergoing open heart surgery. The results were reported in The American Journal of Nephrology (2005;25:318-326).

The study involved 60 children and young adults undergoing cardiopulmonary bypass surgery. The researchers reported finding four distinct urinary biomarkers that predict acute renal injury, based on recent advances in proteomics and proprietary technology from Ciphergen Biosystems, Inc. (Freemont, CA, USA). These biomarkers were then confirmed by conventional methods.

"Despite major achievements in treating patients with kidney failure, little has changed in the last four decades to enable early diagnosis of kidney failure before it progresses to a potentially deadly condition,” observed Dr. Prasad Devarajan, professor of pediatrics and developmental biology at Cincinnati Children's Hospital Medical Center (OH, USA), who led the study. Dr. Devarajan noted that the Ciphergen method that detects proteins captured on protein biochips is rapid, enabling researchers to identify the key proteins in urine with a turn-around time of only 90 minutes and requiring only a microliter of urine.

By identifying the first signs of kidney problems following surgery in a matter of hours, doctors can launch therapeutic measures immediately. Currently, doctors measure changes in serum creatinine, a waste product of protein metabolism found in muscle and blood and excreted in normal urine. However, evaluating creatinine levels in the blood is considered an unreliable indicator of sharp changes in kidney function.

The researchers pointed out that everyone in the study started with normal kidney function and similar urinary proteomic patterns. Yet for 25% of the group, their cardiac surgery led to acute renal failure that was predictable, based on their biomarker patterns. The participants provided urine samples before their surgery, two hours after surgery, and again at six hours after surgery. Researchers found that 15 of the 60 participants subsequently developed renal failure. These patients were found to have a 50% or greater increase in serum creatinine after their procedures. All patients who subsequently developed acute renal failure revealed characteristic changes in their urine biomarker patterns within two hours of their surgery.

"In addition to cardiac surgery patients, this method and test could be very useful in the early diagnosis and prediction of kidney surgery in a variety of other common clinical situations, including kidney transplantation, abdominal surgery, trauma, bleeding, shock, myocardial infarction, stroke, sepsis, and the use of nephrotoxic medications such as antibiotics and chemotherapy,” said Dr. Devarajan.





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