Finding the cause of acute kidney injury: Which index of fractional excretion is better?

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Diskin et al (2010)

In 2010, Diskin et al33 published a prospective, observational study of 100 consecutive patients with oliguric azotemia referred to a nephrology service. They defined acute kidney injury as serum creatinine concentration greater than 1.9 mg/dL and urine output less than 100 mL in 24 hours. They used a higher FEU cutoff for prerenal azotemia of less than 40% to reflect the known urea secretion rate in oliguric patients (600 mL/24 hours). They used an FENa of less than 1% and greater than 3% to distinguish prerenal azotemia from acute tubular necrosis.

Findings. The FEU was more accurate than the FENa, giving the right diagnosis in 95% vs 54% of cases (P < .0001). The difference was exclusively due to the FEU’s greater utility in the 67 patients who had received diuretics (98% vs 49%, P < .0001). Both the FEU and the FENa accurately detected acute tubular necrosis. As expected, the FENa outperformed FEU in the setting of infection, in which cytokine stimulation interferes with urea excretion.

Limitations of the study. Approximately 80% of the patients had prerenal azotemia, potentially biasing the results toward a test geared toward detecting this condition. However, since prerenal causes are more common than intrinsic causes, the authors argued that their cohort more accurately reflected the population encountered in clinical practice.

Additionally, only patients with oliguria and more advanced kidney injury (serum creatinine > 1.9 mg/dL) were included in the study, potentially limiting the applicability of these results in patients with preserved urine output in the early stages of renal failure.

The authors concluded that the FEU should be used in patients with suspected prerenal azotemia on diuretic therapy and should not be used in patients with sepsis.

Table 2 summarizes the findings of the studies discussed above.8,15,30,32,33


The FEU has also been validated in populations at the extremes of age.

In children, Fahimi et al34 performed a cross-sectional study in 43 patients referred to a nephrology service because of acute kidney injury.

An FEU less than 35% had greater sensitivity and specificity than an FENa less than 1% for differentiating prerenal from intrinsic causes in pediatric populations. An FEU of less than 30% had an even greater power of distinguishing between the two. Interestingly, 15 of the 26 patients in the group with prerenal azotemia had an FENa greater than 1%, 8 of whom had an obvious cause (diuretic therapy in 5, salt-losing congenital adrenal hyperplasia in 2, and metabolic alkalosis in 1).

In elderly people, urinary indices are less reliable because of reduced sodium and urea reabsorption and urinary concentrating capability. Thus, the FENa and FEU are increased, making the standard cutoff values unreliable and unpredictable for distinguishing prerenal from intrinsic causes of acute kidney injury.35


Both the FENa and the FEU have been validated in prospective trials as useful clinical indices in identifying prerenal azotemia. Results of these studies vary as to which index is superior and when. This may be attributable to the various definitions of acute kidney injury and diagnostic criteria used in the studies as well as the heterogeneity of patients in each study.

However, the preponderance of evidence indicates that the FEU is more useful than the FENa in patients on diuretics. Since diuretics are widely used, particularly in acute care settings in which acute kidney injury is prevalent, the FEU is a useful clinical tool and should be utilized in this context accordingly. Specifically, when there is a history of recent diuretic use, the evidence supports ordering the FEU alone, or at least in conjunction with the FENa. If the two indices yield disparate results, the physician should look for circumstances that would alter each one of them, such as sepsis or an unrecognized dose of diuretic.

In managing acute kidney injury, distinguishing prerenal from intrinsic causes is a difficult task, particularly because prolonged prerenal azotemia can develop into acute tubular necrosis. Therefore, a single index, calculated at a specific time, often is insufficient to properly characterize the pathogenesis of acute kidney injury, and a combination of both of these indices may increase diagnostic sensitivity and specificity.36 Moreover, urine samples collected after acute changes in volume or osmolarity, such as blood loss, administration of intravenous fluids or parenteral nutrition, or dialysis may compromise their diagnostic utility, and care must be taken to interpret the results in the appropriate clinical context.

The clinician must be aware of both the respective applications and limitations of these indices when using them to guide management and navigate the differential diagnosis in the appropriate clinical settings.

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