Limitations of Fractional Excretion of Urea in Clinical Practice.

Abstract

Potential conflict of interest: Nothing to report. To The Editor: We read an article written by Patidar et al.1 with interest. The researchers performed an analysis in patients with cirrhosis who were taking diuretics and diagnosed with acute kidney injury (AKI). The objective was to determine the diagnostic ability of fractional excretion of urea (FEUrea) to differentiate prerenal azotemia (PRA), type 1 hepatorenal syndrome (HRS), and acute tubular necrosis (ATN). The researchers concluded that FEUrea was an excellent tool for differential diagnosis of AKI in patients with cirrhosis. However, there are limitations of applying FEUrea in clinical settings that should be considered. FEUrea is one of several diagnostic tools to differentiate causes of AKI. Low FEUrea (≤35%) has greater sensitivity and specificity than fractional excretion of sodium (FENa) in differentiating between AKI attributed to PRA and ATN when diuretics are used.2 The diagnostic ability to diagnose PRA for both FENa and FEUrea were assessed in the oliguric state (urine output <500 mL/day). As urine flow increases, FENa and FEUrea are lower and therefore the calculated cutoffs might have to be decreased.3 In this study, urine output was not documented, and it is unknown whether the cutoffs for FEUrea would be different between patients with oliguric and nonoliguric AKI. Therefore, the diagnostic accuracy of FEUrea may vary in nonoliguric AKI. Moreover, using FEUrea to differentiate HRS versus PRA will be challenging because of poor sensitivity (68%) and moderate specificity (80%) in the validation cohort. Other limitations of FEUrea include its interpretation when patients are taking medication that interfere with tubular secretion of creatinine, such as cimetidine and trimethoprim, and clinical situations that interfere with urea transporters or urea cycling, such as infectious diarrhea or sepsis.4 Including these limitations in the study would be worthwhile. Apart from FEUrea, urine microscopy can be an invaluable diagnostic tool to differentiate PRA versus ATN. Evidence showed that the urinary sediment scoring system was highly predictive of diagnosis of ATN. Urine sediment examination can also provide information for other causes of AKI, such as acute glomerulonephritis and acute interstitial nephritis. Because the test can provide very quick information and is relatively cheaper than FEUrea, it should be emphasized as one of the first tools in diagnosis of AKI. In conclusion, there are limitations in using and interpreting FEUrea to differentiate cause of AKI. Clinical advantages of urine microscopy and examination should be stressed.