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16-01-2012 | Cardiology | Article

Urinary biomarkers help detect kidney injury in the ED


Free abstract

MedWire News: Urinary biomarkers of nephron damage help to identify emergency department (ED) patients who have subclinical kidney damage, shows a multicenter study.

"Our analysis prospectively validated the concept that the addition of urinary biomarkers and their interpretation together with sCr [serum creatinine] levels identified patients at risk who otherwise would have been missed during triage," say Kai Schmidt-Ott (Max Delbrück Center for Molecular Medicine, Berlin, Germany) and colleagues.

The research was conducted in one German and two US centers and involved 1635 unselected patients who were admitted to hospital from the ED and remained there for at least 24 hours.

The researchers note that their study was "limited by the absence of a diagnostic gold standard" for intrinsic acute kidney injury (iAKI). They say: "We addressed this limitation by establishing a standardized adjudication procedure to define iAKI, which was based on sCr dynamics, the etiology of AKI, and the response to therapy considering kidney physiology in addition to AKI pathogenesis."

With this approach, the team was able to assign 75.5% of patients to a diagnostic category - 96 to iAKI, 254 to prerenal (p)AKI, 154 to stable chronic kidney disease, and 730 to normal renal function.

Overall, urinary neutrophil gelatinase-associated lipocalin (uNGAL) was the most useful biomarker, giving good discriminatory ability in area under the receiver operating characteristic curve analysis. Urinary kidney injury molecule (KIM-1) and urinary liver-type fatty acid binding protein had fair discriminatory ability and urinary cystatin C and interleukin-18 had poor discriminatory ability.

Notably, sCr level at presentation and its change from baseline discriminated iAKI patients better than did any of the urinary biomarkers.

"This may in part be related to the fact that sCr level was a major determinant of the diagnostic adjudication procedure itself and that most patients had already achieved their peak RIFLE [risk, injury, failure, loss of function, end-stage renal disease] severity class at presentation to the ED," say the researchers.

However, sCr levels in the middle tertile (0.9 to 1.2 mg/dL) had poor discriminatory value, and nearly 40% of patients did not have baseline sCr values recorded.

"This […] implies that urinary biomarkers will be most useful when sCr dynamics are unknown or when the sCr level is in the middle of its range," the team writes in the Journal of the American College of Cardiology.

uNGAL, with a cutoff at the 75th percentile (104 ng/mL), had a sensitivity and specificity for iAKI of 68% and 81%, respectively. With a cutoff at the 60th percentile (47 ng/mL), the corresponding values were 82% and 67%.

In all, 4.4% of patients required dialysis or died in hospital; this occurred in 33.3% of patients with iAKI, compared with just 1.8% of those without. When stratifying patients into three risk categories for this outcome (<2%, 2-15%, >15%), adding uNGAL to sCr resulted in a net reclassification improvement of 26.1%. Adding uKIM-1 to sCr resulted in a net reclassification improvement of 23.8%.

"In contrast, the combination of uNGAL and uKIM-1 did not further improve risk classification, nor were we able to find evidence of the superiority of one of the two markers in head-to-head comparisons," say the researchers.

By Eleanor McDermid

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