New urine tests may help predict kidney problems post surgery

Oct 26 2009

Two studies presented at this week's Annual Meeting of the American Society of Anesthesiologists offer new information as to how physicians might better determine which surgical patients may be at risk for developing kidney injury after surgery.

Acute kidney injury is a common complication in patients admitted to the intensive care unit (ICU) and in those undergoing heart surgery. About 1 in 5 ICU patients will develop acute kidney injury, and it will occur in anywhere from 20-30 percent of adult heart surgery patients.

In the study focused on patients admitted to the ICU, Evan Kharasch, M.D., Ph.D., and colleagues from the Washington University School of Medicine, St. Louis, compared two new urine tests that might soon be used to predict which patients are likely to develop kidney problems after surgery.

These new tests - the NGAL test and KIM-1 test - measure small protein molecules that are released by the kidney cells in response to injury.

"In developing new tests, it is important to determine both the sensitivity and specificity of the test," said Dr. Kharasch.

One important factor Dr. Kharasch found that could skew test results was the presence of undetected kidney cancer, which accounts for 3 percent of adult malignant cancers and often has no symptoms.

Dr. Kharasch noted that patients with kidney cancer had greater levels of KIM-1 in their urine than regular surgical patients and healthy study volunteers. The KIM-1 test also was able to indicate the stage and severity of the tumor.

"Our results show that kidney cancer increases the concentrations of KIM-1 in urine," said Dr. Kharasch. "This suggests that kidney cancer can be a confounder if urine KIM-1 concentration is used as a test for acute kidney injury."

NGAL concentrations in the kidney cancer patients were no different than the other surgical patients and the healthy volunteers. There also was no relationship between urine NGAL and kidney cancer stage or severity.

NGAL levels were the focus of a study by H.T. Lee, M.D., Ph.D., and his research group from the College of Physicians and Surgeons at Columbia, who are the first to report the significance of baseline kidney function when trying to predict with NGAL tests which patients will develop kidney problems.

"Baseline kidney function" is simply a term used to describe how the kidneys were functioning before they were injured.

In previous studies of children undergoing heart surgery, presurgical NGAL tests were able to predict kidney injury almost 100 percent of the time. However, only patients with normal kidneys before surgery were included in these studies.

Dr. Lee said that NGAL appears much less able to identify actute kidney injury in studies of adult heart surgery that include patients with a wide spectrum of baseline kidney function.

To understand this discrepancy, Dr. Lee studied 426 adult heart surgery patients with a wide range of pre-surgical kidney function and hypothesized that the relationship between NGAL and kidney injury would be influenced by baseline kidney function and that grouping these patients by their respective levels of kidney function would improve the ability of NGAL to identify those who may experience kidney injury.

Dr. Lee's research group found that NGAL tests were highly accurate at predicting kidney injury after surgery, but only for those who had normal baseline kidney function before surgery.

"For all other groups of baseline kidney function," said Dr. Lee, "NGAL was no better than chance at identifying acute kidney injury within 24 hours of surgery."

One possible explanation for this discrepancy, said Dr. Lee, is that significant pre-existing kidney damage limits the ability of the kidneys to rapidly synthesize and release NGAL in response to injury.

Although Dr. Lee's study supports the utility of using NGAL tests in heart surgery patients who have normal kidney function, the test seems to offer little benefit to the 25-30 percent of patients with impaired kidney function, the group most at risk of suffering kidney injury during or after surgery.

"Further studies are under way to confirm or refute our findings," said Dr. Lee. "However, if confirmed, they represent an important step forward in our understanding of the clinical use of NGAL for the early diagnosis of acute kidney injury."