Urine Na⁺ excretion is influenced by a number of hormonal and other factors. Changes in water excretion by the kidney can result in changes in urine Na⁺ concentration [Na⁺] . For example, patients with diabetes insipidus can excrete 10 L of urine per day. Their urine [Na⁺] may be inappropriately low due to dilution, suggesting the presence of volume depletion. Conversely, increased water reabsorption by the kidney can raise the urine [Na⁺] and mask the presence of hypovolemia. To correct for water reabsorption, the renal handling of Na⁺ can be evaluated directly by calculating the FE_Na, which is defined as the ratio of urine to plasma Na⁺ divided by the ratio of urine (U_Cr) to plasma creatinine(P_Cr), multiplied by 100.

The FE_Na is the excreted fraction of filtered Na⁺. The major use of FE_Na is in patients with AKI . Patients with prerenal azotemia have low (< 1 %) FE_Na compared to patients with acute tubular necrosis (ATN) , whose FE_Na is generally high (> 2 %). When ATN is superimposed on decreased effective arterial blood volume due to hepatic cirrhosis or congestive heart failure, the FE_Na is < 2 % because of the intense stimulus to Na⁺ reabsorption. Similarly, patients with ATN, due to radiocontrast agents or rhabdomyolysis have low FE_Na for unknown reasons.

It was shown that FE_Na in children with nephrotic syndrome is helpful in the treatment of edema with diuretics. In these patients, FE_Na < 0.2 % is indicative of volume contraction, and > 0.2 % is suggestive of volume expansion. Therefore, patients with FE_Na > 0.2 % can be treated with diuretics to improve edema.

The FE_Na is substantially altered in patients on diuretics . In these patients, the FE_Na is usually high despite hypoperfusion of the kidneys. In such patients, the FE_Urea may be helpful. In euvolemic subjects, the FE_Urea ranges between 50 and 65 %. In a hypovolemic individual, the FE_Urea is < 35 %. Thus, a low FE_Urea seems to identify those individuals with renal hypoperfusion despite the use of a diuretic .

Uric acid excretion is increased in patients with hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH) secretion or syndrome of inappropriate antidiuresis and cerebral salt wasting. As a result, serum uric acid level in both conditions is low (< 4 mg/dL). Since serum uric acid levels are altered by volume changes, it is better to use FE_UA. In both SIADH and cerebral salt wasting, FE_UA is > 10 % (normal 5–10 %). In order to distinguish these conditions, FE_PO4 is used. In SIADH, the FE_PO4 is < 20 % (normal < 20 %), and it is > 20 % in cerebral salt wasting.

Transtubular K⁺ gradient (TTKG) is an indirect measure of K⁺ secretion in the distal nephron (cortical collecting duct and to some extent late distal convoluted tubule). In a healthy individual, determination of urine [K⁺] reflects the amount of dietary K⁺ because of its secretion in the distal nephron. TTKG reflects the activity of aldosterone, the major hormone that regulates K⁺ secretion. In hypokalemic and hyperkalemic conditions, the urinary excretion of K⁺ is low and high, respectively. However, water reabsorption in the cortical and medullary collecting ducts is an important determinant of urinary K⁺ concentration. For example, an increase in water reabsorption increases and a decrease in water reabsorption decreases urine [K⁺]. Therefore, an appropriate method to calculate urine [K⁺] is the transtubular K⁺ gradient (TTKG) , which is calculated as follows:

where U_K and P_K are urine and plasma K⁺ concentrations, respectively, and P_Osm and U_Osm are plasma and urine osmolalities, respectively. The urine to plasma osmolality ratio is used to correct the [K⁺] in the urine for the amount of water reabsorbed in the distal nephron. TTKG is mostly useful in the evaluation of patients with hyperkalemia, but it can also be used in the evaluation of hypokalemia.

In normal subjects on a regular diet, the TTKG varies between 6 and 8. A TTKG value < 5–7 in a patient with hyperkalemia indicates impaired distal tubular secretion of K⁺ due to aldosterone deficiency or resistance. Patients with mineralocorticoid excess should have a TTKG > 10. In a patient with hypokalemia, the distal nephron should decrease the secretion of K⁺, and a TTKG value should be < 2.

Two assumptions must be met before using the TTKG formula: (1) there must be adequate ADH activity, which is verified by measuring urine osmolality that should exceed serum osmolality, and (2) there must be adequate delivery of filtrate to the distal nephron for K⁺ secretion. This can be verified by determining urine Na⁺, which should be > 25 mEq/L.

Urine anion gap (U_AG) is an indirect measure of NH₄ ⁺ excretion, which is not routinely determined in the clinical laboratory. However, it is measured by determining the urine concentrations of Na⁺, K⁺, and Cl⁻ and is calculated as [Na⁺] + [K⁺] − [Cl⁻]. In general, NH₄ ⁺ is excreted with Cl⁻. A normal individual has a negative (from 0 to −  50) U_AG (Cl⁻ > Na⁺ + K⁺), suggesting adequate excretion of NH₄ ⁺. On the other hand, a positive (from 0 to + 50) U_AG (Na⁺ + K⁺ > Cl⁻) indicates a defect in NH₄  excretion. The U_AG is used clinically to distinguish primarily hyperchloremic metabolic acidosis due to distal renal tubular acidosis (RTA) and diarrhea. Both conditions cause normal anion gap metabolic acidosis and hypokalemia. Although the urine pH is always > 6.5 in distal RTA, it is variable in patients with diarrhea because of unpredictable volume changes. The U_AG is always positive in patients with distal RTA, indicating reduced NH₄ ⁺ excretion, whereas, it is negative in patients with diarrhea because these patients can excrete adequate amounts of NH₄ ⁺. Also, positive U_AG is observed in acidoses that are characterized by low NH₄ ⁺ excretion (type 4 RTA).