Hyponatremia—What Is Cerebral Salt Wasting?

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Jasminder Momi, MD; Christopher M Tang, MD; Antoine C Abcar, MD; Dean A Kujubu, MD; John J Sim, MD

Summer 2010 - Volume 14 Number 2



Background: Hyponatremia is a common electrolyte imbalance in hospitalized patients. It is associated with significant morbidity and mortality, especially if the underlying cause is incorrectly diagnosed and not treated appropriately. Often, the hospitalist is faced with a clinical dilemma when a patient presents with hyponatremia of an unclear etiology and with uncertain volume status. Syndrome of inappropriate antidiuretic hormone (SIADH) is frequently diagnosed in this clinical setting, but cerebral salt wasting (CSW) is an important diagnosis to consider.

Objective: We wanted to describe the diagnosis, treatment, and history of CSW to provide clinicians with a better understanding of the differential diagnosis for hyponatremia.

Conclusion: CSW is a process of extracellular volume depletion due to a tubular defect in sodium transport. Two postulated mechanisms for CSW are the excess secretion of natriuretic peptides and the loss of sympathetic stimulation to the kidney. Making the distinction between CSW and SIADH is important because the treatment for the two conditions is very different.

Case Presentation

A man, age 43 years, is evaluated for hyponatremia. He was admitted to the hospital six days earlier for an intracranial hemorrhage that required emergency evacuation. The patient was later extubated when his neurologic status improved. His medical history includes poorly controlled hypertension and rheumatoid arthritis.

On hospital day 6, his serum sodium level is noted to be 121 mEq/L. He has been receiving 0.9% normal saline since admission, and his sodium level has been gradually decreasing from 141mEq/L, the level at admission. A hyponatremia workup reveals a low serum osmolarity of 256 mOsm/kg, a normal serum creatinine level of 0.6 mg/dL, a urine sodium level of 89 mmol/L, and an inappropriately high urine osmolarity of 588 mOsm/kg. His urinalysis reveals a specific gravity of 1.030, with no blood or protein. His levels of serum thyroid-stimulating hormone and random cortisol are within normal limits. His brain natriuretic peptide (BNP) and fractional excretion of uric acid are elevated, at 686 pg/mL and 83.8%, respectively.

The patient appears euvolemic, with a blood pressure of 115/70 mm Hg and pulse of 90 beats per minute. His intake and outtake documentation reveals that his urine output has been 2 to 4 L/d despite a fluid restriction of <1.5 L/d that was initiated two days earlier. His sodium level has continued to decline after the fluid restriction. The working diagnosis is syndrome of inappropriate antidiuretic hormone (SIADH).


Hyponatremia (sodium level of <136mEq/L) has been associated with confusion, lethargy, seizures, coma, and even death.1 The differential diagnosis for hyponatremia is broad and includes hormone disorders (eg, thyroid and adrenal insufficiency), medications, and volume-related problems. In the acute-care setting, hyponatremia has been reported to occur in up to 30% of patients with subarachnoid hemorrhage (SAH).2,3 The physician often faces a clinical dilemma when hyponatremia has an unclear etiology and volume status is uncertain. Early and accurate diagnosis of the etiology of the hyponatremia is important in order to institute proper therapy. An incorrect diagnosis can cause significant morbidity and mortality.

SIADH is a frequent diagnosis in a patient with hyponatremia and a concurrent intracranial process.4 However, cerebral salt wasting (CSW) is an important diagnosis to consider and differentiate from SIADH.

CSW was first described by Peters et al in 19505 when they reported the cases of three patients with an intracranial process who exhibited renal salt wasting, but the existence of CSW was questioned after the identification of SIADH in 1957 by Schwartz et al.6 For years afterward, CSW was considered either a condition that was an element of SIADH or one that did not exist. CSW now is again being recognized as a separate entity altogether. A retrospective review of data for 316 patients who presented with SAH and hyponatremia found that the diagnosis was SIADH in 69% and was CSW in 6.5%.7 Both conditions have been reported to occur in the setting of head trauma, intracranial or metastatic neoplasm, carcinomatous or infectious meningitis, SAH, and central nervous system surgery.8 The distinction between these two conditions is important because their treatments are different.


CSW and SIADH share many similar laboratory and clinical findings (Table 1). Both conditions present with low serum osmolality, high urine osmolality, and a high urine sodium level. The fundamental difference between the two processes is the extracellular fluid volume (ECFV) status. CSW is defined by the renal loss of salt with concomitant extracellular fluid loss.2,3,8-10 Consequently, patients with CSW have hypovolemia compared with patients with SIADH, who have euvolemic or mild ECFV expansion. The clinical history and assessment findings may be helpful if postural blood pressure changes, tachycardia, or poor skin turgor are present. Unfortunately, this difference is not always clinically apparent. In a study conducted by Chung et a11 to evaluate the clinical assessment of the ECFV status in 58 patients without edema and hyponatremia, only 47% of those with hypovolemia and 48% of those with euvolemia were accurately classified.

Uric acid excretion may be one measure for differentiating between CSW and SIADH. Initially, both conditions are associated with a low serum uric acid level and a high fractional excretion of uric acid.4,8,9 Uric acid is normally resorbed in the proximal tubule along with sodium. In SIADH, sodium resorption in the proximal tubule may be decreased because of an expanded ECFV, which can lead to less uric acid absorption and increased uric acid loss in the urine. Another contributing mechanism in SIADH, proposed by Decaux et al,12 involves the stimulation of the V1 receptor by antidiuretic hormone, which enhances excretion of uric acid in the renal tubules. The exact mechanism of uric acid loss in CSW has not been well defined. It is generally believed to be part of the solute diuresis that occurs in CSW with impaired urate transport in the proximal tubules.4,8 The key differentiation is that patients with SIADH have a serum uric acid level and fractional excretion of uric acid that normalize after correction of the serum sodium level, whereas the uric acid level remains low and uric acid excretion remains elevated in patients with CSW, despite correction of hyponatremia.2,4,8,9

Response to fluid therapy is also a key distinction between SIADH and CSW. The treatment of choice for SIADH is free water restriction when increased fluid intake will worsen the hyponatremia. In contrast, CSW is a volume-depleted and sodium-wasting state requiring fluid replacement with isotonic solutions.

The renal wasting of sodium in CSW is poorly understood. Two postulated mechanisms are disruption of sympathetic neural input to the kidney and natriuresis induced by natriuretic peptides. Both mechanisms can lead to downstream inhibition of the renin-angiotensin-aldosterone system.2,4,8,9 Sympathetic stimulation normally causes proximal tubule absorption of sodium. Depression of this sympathetic input to the kidney results in less sodium resorption in the proximal tubule and an increase in sodium delivery to the distal tubule. This leads to a decrease in the effective arterial blood volume, triggering the baroreceptors to release antidiuretic hormone to help maintain intravascular volume. A depressed sympathetic drive has also been associated with a decrease in renin and aldosterone levels, further inhibiting sodium retention.2,4,8,9

Elevated natriuretic peptides levels have been described with CSW.13 Atrial natriuretic peptide (ANP) and BNP have both been studied in patients with intracranial pathology and hyponatremia. Although both ANP and BNP have been described to be elevated for up to two weeks, BNP elevation is more consistent. BNP is primarily released by the cardiac ventricles in response to the increased ECFV but can also be secreted by the brain.13 The natriuretic peptides have been described as causing direct tubular inhibition of sodium resorption and inhibition of intramedullary collecting-duct sodium absorption.8,9,13 They are also believed to cause direct inhibition of renin and aldosterone release from the juxtaglomerular cells and the adrenal gland, respectively.8,9,13

Berendes et al13 studied BNP levels in patients with an intracranial process and compared them with study control participants. Sixty patients were divided into three groups. Group 1 included 10 patients with SAH who underwent clipping of ruptured aneurysms within 24 hours, group 2 included 10 patients with intracranial tumors who underwent craniotomy, and group 3 included 40 healthy individuals. Natriuretic peptides (ANP, BNP), aldosterone, renin, and antidiuretic hormone levels were assessed before surgery and at 1 hour, 4 hours, 12 hours, and daily for 7 days after surgery. Patients with SAH had elevated baseline BNP levels but normal ANP levels when compared with healthy individuals. Urine output and urinary excretion of sodium were greater in the SAH group than in the other groups. Aldosterone levels were also lower in this group. BNP appeared to be the primary natriuretic peptide that caused salt wasting in patients with SAH.


Early appropriate therapy of hyponatremia is important to prevent complications. CSW is a volume-depleted state treated with intravenous administration of isotonic or hypertonic fluids to obtain positive fluid balance and correct volume depletion. Depending on the acuity and clinical manifestation of the hyponatremia, isotonic or hypertonic solutions would be indicated. Additionally, sodium tablets can be combined with the intravenous fluids. Doses of sodium of up to 12 g/d may be used.2 Rapid correction of the serum sodium by more than 12 mmol/d should be avoided because of the risk of osmotic demyelination.1 Once euvolemia is achieved, the goal of therapy is to maintain a positive salt balance and to prevent volume depletion by matching the urinary output with volume repletion.

Fludrocortisone, a potent mineralocorticoid, has also been used for the treatment of CSW at doses of 0.1 to 1 mg/d. It exerts its effects by stimulating reabsorption of sodium and water in the distal tubule, leading to expansion of the ECFV. When fludrocortisone therapy was used in patients with SAH, less natriuresis occurred and sodium balance was achieved more frequently.14,15 Thus, volume depletion and hyponatremia are preventable in patients treated with fludrocortisone. The most common adverse effect associated with fludrocortisone was hypokalemia, which was observed in up to 73% of patients.15

The length of therapy depends on the clinical course of the hyponatremia and the underlying pathology associated with CSW (Table 2). Once the underlying pathology is corrected, CSW is usually a transient condition that resolves within three to four weeks. Hence, long-term therapy is usually not needed.9

Case Outcome

The case presented here illustrates the dilemma that clinicians face. The patient's condition did not respond to fluid restriction, although his laboratory test results and presentation appeared to suggest SIADH. However, the fact that his hyponatremia continued to worsen with fluid restriction raised some questions. In addition, his fractional excretion of uric acid was persistently elevated. The patient also continued to have a high urine output. He was immediately given isotonic saline, keeping his net fluid balance positive. The serum sodium level started to improve, but he continued to require 3 L to 4 L of isotonic saline daily to keep his fluid balance between even and positive. Although there is no absolute certainty in a diagnosis of a clinical syndrome, the patient's condition was diagnosed as probable CSW. He was eventually discharged with a serum sodium level of 140 mEq/L.


Hyponatremia in the setting of a central nervous system event is a diagnostic challenge to physicians. Both SIADH and CSW are likely etiologies, as they present with very similar biochemical profiles. Levels of natriuretic peptides and changes in fractional excretion of uric acid may help differentiate between the two conditions. The key difference is that SIADH is a euvolemic to mildly hypervolumic state, whereas CSW is a volume-depleted state. Unfortunately, the volume status is not always clinically apparent in every patient. It is important to consider CSW in addition to SIADH in patients who present with hyponatremia and an intracranial process. A correct and timely diagnosis is important in order to obtain a good outcome, because the two conditions are treated very differently.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


Katharine O'Moore-Klopf, ELS, of KOK Edit provided editorial assistance.

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