A 50-year old woman naive to the health care system presents to the ED with nausea, malaise, and decreased exercise tolerance for several weeks. Physical exam reveals mild bilateral lower extremity edema. Her labs are notable for an elevated creatinine of 7.0. She is admitted for work-up of her renal disease.
Nephrology was consulted and recommended obtaining urine electrolytes. The admitting hospitalist is unsure which urine electrolytes are appropriate to order, and in turn orders all of the urine electrolytes in the order set.
Which urine electrolytes should be ordered in various clinical contexts?
Hospitalists have been on the forefront of efforts to tailor testing and resource utilization to eliminate wasteful practices in health care. To order and interpret diagnostic tests appropriately, a hospitalist needs to have a thorough understanding of the diagnostic utility of laboratory tests. There is a lack of clear diagnostic guidelines, so ordering all the urine electrolytes in a “blanket” strategy is a common practice. We will discuss the diagnostic utility of each of the urine electrolytes in a variety of clinical scenarios.
Acute kidney injury
Both the fractional excretion of sodium (FENa) and the fractional excretion of urea (FEUrea) have long been used as part of the standard work-up for determining if acute kidney injury (AKI) is due to prerenal causes. Although these markers prove to be beneficial in the work-up of AKI, both the FENa and FEUrea have several 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 may indicate prerenal azotemia, as an increased reabsorption of sodium is the appropriate response of functioning nephrons to decreased renal perfusion. Values greater than 3% may be consistent with acute tubular necrosis (ATN) due to inappropriate sodium excretion in the setting of tubular damage.
Importantly, a FENa value of less than 1% occurs in a number of conditions other than prerenal azotemia due to dehydration, including hypervolemic prerenal states such as cirrhosis or heart failure; AKI due to radiocontrast or heme pigments; acute glomerulonephritis; transition from prerenal to postischemic ATN or sepsis, and in acute interstitial nephritis (AIN).1,2 Approximately 10% of patients with nonoliguric ATN have a FENa less than 1.0%. Moreover, use of diuretics can falsely elevate the FENa due to inhibition of sodium reabsorption. FENa values above 3% can occur in volume contraction in patients with chronic kidney disease (CKD) or in elderly patients as their sodium reabsorption is impaired.3 Acute volume loss (e.g. blood loss), or more commonly, administration of diuretics or intravenous fluids, can also alter the interpretation of the FENa.2
When is the FENa reliable? FENa measurements were first validated and studied in patients with a marked reduction in glomerular filtration rate (GFR) and oliguria.2 Subsequent studies have shown that when patients are oliguric, the FENa is more accurate.3 The FENa 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.3 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 will theoretically 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.2
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.2 Its interpretation also relies on intact functioning of the proximal tubule, which can be altered in many conditions including uncontrolled diabetes. Overall, the FENa and FEUrea can be helpful to determine the etiology of AKI, but only in certain clinical scenarios.
Hyponatremia is the most common electrolyte abnormality in hospitalized patients, with a prevalence of up to 30% in critically ill patients.4 It often is acquired during the hospitalization itself. A detailed history and physical exam, including careful assessment of volume status, is as important as laboratory values in establishing the cause of hyponatremia.
Urine sodium and urine osmolality are measured to understand whether the renin-aldosterone-angiotensin system (RAAS) and antidiuretic hormone (ADH) are activated. If renal blood flow or renal delivery of sodium is decreased, renin secretion from the juxtaglomerular apparatus will be activated, ultimately leading to increased reabsorption of sodium in the distal tubules and collecting ducts. Thus, low urine sodium signals that the RAAS is activated due to decreased serum sodium concentration or decreased renal blood flow from hypovolemia or low effective arterial circulation from cirrhosis or heart failure.
Most causes of hyponatremia will have low urine sodium values, including hypovolemia, cirrhosis, heart failure, “tea-and-toast” diet, beer potomania, and primary polydipsia. However, the urine sodium may be unreliable in patients who are not oliguric or who have CKD.
Diuretic-induced hyponatremia from thiazide or loop diuretics will likely have elevated urine sodium levels. Similarly, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) will have an elevated urine sodium above 20-40 mEq/L.
Urine osmolality becomes elevated when ADH is secreted in response to reduced plasma volume or increased plasma osmolality. Urine osmolality is low in cases such as primary polydipsia, which creates a maximally dilute urine of 40-100 mEq/L, and in tea-and-toast diets or beer potomania due to low solute intake. Urine osmolality can be elevated in hypovolemic states as well as SIADH, and is variable in hypothyroidism and selective serotonin reuptake inhibitor administration. Thus, urine sodium, and not urine osmolality, is the most useful differentiator between SIADH and hypovolemic states.
In a study of 555 patients with hyponatremia secondary to SIADH, mean urine sodium was found to be 72 (range 30-251) and the median urine osmolality was 379 (range 123-1019).5
In cases of marked hyperglycemia, serum osmolality should be measured to evaluate hyperglycemia as a cause of hyperosmolar hyponatremia. Pseudohyponatremia in the setting of hyperlipidemia, hypertriglyceridemia, or hyperparaproteinemia represents a laboratory artifact due to lower plasma water concentration in the specimen sample and should be excluded.