Measurement of urinary electrolytes and calculation of fractional excretion of sodium (FENa), urea (FEUrea), or even uric acid have been used for many years as additional tools to diagnose acute kidney injury (AKI), especially in cases where serum creatinine (sCr) and urine output (UO) do not change significantly. However, if these tests are not interpreted correctly they can be misleading; also, reports of their correlation with clinical and histopathological findings have been inconsistent. In situations associated with transient hypovolemia or hypoperfusion, healthy kidneys respond by increasing urine osmolarity and reducing sodium and/or urea or uric acid excretion. However, this physiological response may be variable and confounded by chronic kidney disease (CKD) and interventions such as diuretics, aminoglycosides, and cardiopulmonary bypass. This is particularly relevant for ICU patients in whom critical illness is usually accompanied by fluid overload, muscle wasting, sepsis, and reduced effective circulating volume, all of which may mask the diagnosis of AKI.(1, 2)
Fractional Excretion of Sodium (FENa)
The FENa is a measure of the extraction of sodium and water from the glomerular filtrate. It is the ratio of the sodium filtration rate to the overall glomerular filtration rate (GFR). An euvolemic person with normal renal function and moderate salt intake in a steady state will have FENa approximately 1%. Patients with pre-existing CKD might exhibit FENa >1% in the absence of AKI depending on their GFR and sodium intake. Traditionally FENa has been used to discriminate between pre-renal and intrinsic AKI (in which there is tubular damage leading to an inability to properly reabsorb electrolytes, including sodium).
In pre-renal azotemia, the proximal tubules reabsorb filtered sodium resulting in a very low urine sodium concentration (<20 mmol/L) and FENa <1%, whereas in intrinsic AKI the urine sodium concentration is >40 mmol/L and the resulting FENa is >1%. A low FENa or low urine sodium (together with normal urinary sediment) reflects poor renal perfusion of any cause, not exclusively volume depletion. However there are many reasons why FENa might be low in the setting of intrinsic AKI, or might be high in the setting of pre-renal AKI, including diuretic use, sepsis, myoglobinuria, acute glomerulonephritis, cirrhosis, congestive heart failure, and contrast induced nephropathy. A detailed list of the limitations of FENa is presented by Perazella and Coca.(3, 4)
Fractional Excretion of Urea (FEUrea)
Calculation of FEUrea is based on the same principle as FENa. However, urea reabsorption occurs mainly at the proximal tubule, which should theoretically make FEUrea more reliable than FENa during use of diuretic agents, which act distally to the proximal tubule. However studies evaluating the performance of FEUrea in various clinical settings (including ICU patients) have produced discordant results. A low FEUrea is usually indicative of pre-renal AKI, however recent studies indicate that aging and sepsis may alter FEUrea.(5, 6)
How Can the Clinical Lab Be of Help?
It is easy to implement these calculated tests in a clinical lab’s routine. A fresh random urine collection (not catheterized) is required, together with a blood sample, and calculations can be made within the laboratory information system. However, the utility of standardized interpretive comments for these tests are a matter of debate. Personalized interpretive comments can be made by the Clinical Chemist only if he/she has access to patients history and putative diagnosis, and may be limited by regulatory restrictions.
The interpretation of urinary electrolytes is challenging, with many limitations affecting urine concentrations and fractional excretion indices. Serial monitoring of urinary electrolytes may be more useful than individual measurements, as sequential alterations in urine composition have been shown to parallel the development and severity of AKI. However, whether serial measurement of urine electrolytes can also help diagnosing the etiology of AKI remains unclear.
The original article please refer to AACC CLN News:https://www.aacc.org/community/aacc-academy/publications/scientific-shorts/2018/urinary-sodium-urea-and-fractional-excretion-calculations
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