cerebral salt-wasting syndrome (renal salt wasting)

Lulwah AlThumali

Pediatric ResidentTCH

Objectives

INTRODUCTIONDefinitionPATHOPHYSIOLOGYEtiologyEPIDEMIOLOGYHistoryPhysical Examination

WorkupDIAGNOSISDIFFERENTIAL DIAGNOSISTREATMENTPrognosisSUMMARY 

INTRODUCTION Hyponatremia is a common electrolyte disorder

in the setting of (CNS) disease .

Cerebral salt wasting (CSW) is potential cause of ↓Na˖ in those with CNS disease

Definition cerebral salt-wasting syndrome is defined by the development of extracellular volume depletion due to a renal Na˖ transport abnormality in patients with intracranial disease and normal adrenal and thyroid function

PATHOPHYSIOLOGYThe SNS promotes Na˖, uric acid &water reabsorption in the proximal tubule, as well as renin release. Thus, impaired sympathetic neural input could explain the reductions in proximal Na˖ & urate reabsorption as well as the impaired release of renin and aldosterone. The failure of serum aldosterone to rise in response to volume depletion would explain the absence of potassium wasting despite the increase in distal sodium delivery.

PATHOPHYSIOLOGY

The 2nd theory is that a circulating factor that impairs renal tubular Na˖ reabsorption is released in patients with brain injury. The primary candidate is brain natriuretic peptide (BNP), which decreases Na˖ reabsorption and

inhibits renin release .

mechanisms for cerebral salt-wasting syndromePossible mechanisms for cerebral salt-wasting syndrome. The injured brain may release natriuretic proteins that act directly on the kidney. In addition, cerebral injury may increase sympathetic nervous system activity, elevating renal perfusion pressure and releasing dopamine

Etiology

Head injuryHydrocephalusBrain tumorIntracranial surgeryStrokeIntracerebral hemorrhage Tuberculous meningitis

Craniosynostosis repair

EPIDEMIOLOGY The incidence of CSW is unclear, particularly

given that its existence is disputed . Among patients with CNS disease, cerebral salt wasting is a much less common cause of hyponatremia than SIADH.Although CSW has been most often described in patients with subarachnoid hemorrhage, it accounts for only a small proportion of cases of hyponatremia in these patients (7 percent in one series compared to 69 percent due to SIADH)

History

Hyponatremia and cerebral salt-wasting syndromeAs the decline in serum sodium concentration reduces serum osmolality, a tonicity gradient develops across the blood-brain barrier that causes cerebral edema. Symptoms include lethargy, agitation, headache, altered consciousness, seizures,and coma.

The severity of symptoms typically reflects the magnitude and rapidity of the decrease in serum sodium concentration.Intravascular volume depletionHistorical features suggesting hypovolemia include thirst, abrupt weight loss, decreasing urinary frequency, and negative fluid balance.

Physical Examination

Physical signs intravascular volume depletion

Physical signs associated with severe hyponatremia

orthostatic tachycardia OR hypotension

altered mental status

increased capillary refill time seizures

increased skin turgor coma

dry mucous membranes

sunken anterior fontanel

WorkupThe following lab studies may be indicated in patients with CSW:

Serum Na˖ concentration _ hyponatremicSerum osmolality - If measured serum osmolality exceeds twice the serum sodium concentration and azotemia is not present, suspect hyperglycemia or mannitol as the cause of ↓NaUrinary output - Urine is relatively dilute and the flow rate is often high in CSW

Workup

Urinary Na˖ concentrations

urinary sodium excretion (urinary sodium concentration [mEq/L] x urinary volume [L/24 h]) is substantially higher than sodium intake in CSW syndrome but generally equals sodium intake in SIADH .Therefore ,

net sodium balance (intake minus output) is negative in cerebral salt-wasting syndrome.

WorkupUric acidFractional excretion of uric acid (FEUA) is defined as the percentage of urate filtered by glomeruli that is excreted in urine .

Normal values are less than 10%.Patients with either cerebral salt-wasting syndrome or SIADH can have hypouricemia and elevated FEUA.

However, after correction of hyponatremia, hypouricemia and elevated FEUA may normalize in SIADH but persist in cerebral salt-wasting syndrome (renal salt wasting).]

WorkupPhosphateFractional excretion of phosphate (FEP) should be determined when evaluating patients with hyponatremia and hypouricemia. Elevated FEP suggests cerebral salt-wasting syndrome as opposed to SIADH

DIAGNOSIS  ●Hyponatremia (less than 135 meq/L) with a low

plasma osmolality●An inappropriately elevated urine osmolality

(above 100 mosmol/kg and usually above 300 mosmol/kg)

●A urine sodium concentration usually above 40 meq/L

●A low serum uric acid concentration due to urate wasting in the urineClinical evidence of hypovolemia is crucial since all of these laboratory findings are also seen in SIADH.

DIFFERENTIAL DIAGNOSIS In the setting of CNS injury, CSW must be distinguished from other

causes of hyponatremia, principally SIADH .CSW versus SIADH 

The distinction between CSW and SIADH is critically important since the two disorders are managed differently, with possible adverse consequences if the incorrect therapeutic strategy is administered.

In addition to hyponatremia, the two disorders share the following features:

●The urine osmolality is inappropriately high in the presence of hyponatremia (which normally suppresses ADH release) due to increased release of ADH. This response is appropriate in cerebral salt wasting, due to the volume depletion, but inappropriate in SIADH.

●The urine sodium is usually >40 meq/L due to volume expansion in SIADH and putative salt wasting in CSW.

●The serum uric acid concentration is typically reduced due to urinary losses, perhaps due to a putative hormone such as BNP in CSW and to volume expansion

The differences and similarities in findings for CSW and SIADH 

SIADH CSW

 Present  Present Hyponatremia

Increased Increased Urine Na

normal or increased Reduced Volume

self-limited Gross Salt wasting

variable Polyuria Urine output

frequent  Occasionally Hypouricemia

Blood Pressure Normal - orthostasis Normal

Central Venous Pressure Normal Low

CSW and SIADHOver the years, much debate has been focused on the existence of this entity. The evidence in favor of CSW rests on the following points :

(1 )the presence of a negative salt balance ,(2 )the development of volume contraction (by

definition, patients with SIADH are euvolemic), and

(3 )the fact that patients with CSW respond to salt and volume replacement rather than to fluid restriction.

TREATMENT*correction of intravascular volume depletion and

↓Na ˖*replacement of ongoing urinary sodium loss, usually

with intravenous (IV) hypertonic saline solutions.  * mineralocorticoid therapy in CSW

(Fludrocortisone)

*Once the patient is stabilized, enteral salt supplementation can be considered.

*monitoring of body weight, fluid balance, and serum sodium concentration is essential during the hospital course.

Mineralocorticoids

Class SummaryMineralocorticoids enhance sodium reabsorption in the kidney by direct action on distal tubule cells, resulting in expanded extracellular fluid volume. They increase renal excretion of potassium and hydrogen ion.

 Fludrocortisone promotes the increased reabsorption of sodium and the loss of potassium by the renal distal tubules.

TREATMENT Fluid restriction, the usual first-line therapy for SIADH, may increase the risk of cerebral infarction among patients who actually have CSW since ongoing salt losses might worsen the volume depletion and lower the blood pressure .

Volume repletion with isotonic saline is the recommended therapy in CSW since it will suppress the release of ADH, thereby permitting excretion of the excess water and

correction of the ↓Na .˖ .

Long-Term Monitoring

Patients whose neurologic insult has improved and who demonstrate normal intravascular volume and serum sodium concentrations on enteral salt supplements, fludrocortisone, or both can be closely observed on an outpatient basis until cerebral salt-wasting syndrome resolves.

Prognosis

Cerebral salt-wasting syndrome usually develops in the first week following a brain insult. Its duration is usually brief (spontaneously resolves in 2-4 wk), although it can last for several months. Death and complication rates for this syndrome are not available

SUMMARY AND RECOMMENDATIONS

Cerebral salt wasting (CSW) is characterized by ↓Na˖ and extracellular fluid depletionCSW mimics all of the laboratory findings in the SIADH. The only clue to the presence of CSW rather than SIADH is clinical evidence of extracellular volume depletion, such as hypotension and decreased skin turgor, and/or increased hematocrit

SUMMARY AND RECOMMENDATIONS

In CNS disease, accurate distinction between CSW & SIADH is essential since the two disorders are managed differently.

In patients with a clinical picture compatible with CSW, we recommend initial therapy with isotonic saline to correct the volume depletion

and possibly reverse the ↓Na . ˖

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