Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have an established role as part of the work-up for determining if acute kidney injury (AKI) is due to a prerenal or intrarenal cause. Although both the FENa and FEUrea are helpful, they both have their limitations.
FENa measures the ratio of sodium excreted in the urine compared to how much is filtered through the kidney. A FENa of less than 1% in oliguric patients suggests prerenal azotemia. A FENa greater than 2% is typically seen with acute tubular necrosis (ATN). FENa values between 1-2% is a gray zone and other clinical indicators are needed to establish the cause of AKI.
One big problem is that there are a number of factors that affect the FENa other than volume status. A FENa of less than 1% can also occur in hypervolemic states such as cirrhosis or heart failure, radiocontrast nephropathy rhabdomyolysis with myogloblobinuria, acute glomerulonephritis, and in acute interstitial nephritis (AIN). Also, about 10% of patients with nonoliguric ATN have a FENa less than 1%, so ATN more frequently is associated with elevated FENa values, but it can be decreased in a minority of cases. FENa can be elevated with diuretic use or in patients with chronic kidney disease (CKD) who have impaired sodium reabsorption. In these cases, diuretics or patients with CKD can have elevated FENa values even though they are intravascularly depleted.
The FENa is the most accurate when patients are oliguric. It is best utilized when urine sodium and creatinine are collected at the same time as the serum values, because serum creatinine levels tend to fluctuate with time and are not often accurate markers of GFR. FEUrea is used primarily for diagnostic evaluation in patients who have an AKI with recent use of diuretics. Because urea is absorbed and excreted in the proximal tubule, the value should not be altered by the use diuretics. The FEUrea will be less than 35% in prerenal azotemia and greater than 50% in ATN. The current evidence suggests that the FEUrea is most reliable in diagnosing prerenal azotemia in patients who have used diuretics when the FENa is high but the FEUrea is low.
Many of the limitations of the FENa also apply to the FEUrea, including interpretation in the elderly and use in acute volume changes. However, the FEUrea has unique limitations, particularly in patients with sepsis, as cytokines released in sepsis may interfere with urea transporters in the kidney and colon. The interpretation of FEurea also relies on the intact functioning of the proximal tubule. Overall, the FENa and FEUrea are helpful to determine the etiology of AKI as individual data points, but it is important to know their limitations. Always use these values to support your clinical suspicion, not to change your clinical thoughts.