How to manage hyponatremia in a patient with Acute Kidney Injury (AKI)?

Management of Hyponatremia in Acute Kidney Injury

In patients with AKI and hyponatremia, immediately withdraw diuretics and nephrotoxic drugs, assess volume status to determine the underlying cause (hypovolemic, euvolemic, or hypervolemic), and initiate cause-specific treatment while carefully monitoring sodium correction rates to avoid osmotic demyelination syndrome. 1

Initial Assessment and Risk Factor Removal

The first critical step is identifying and removing precipitating factors:

• Immediately discontinue all diuretics, nephrotoxic medications (NSAIDs, ACE inhibitors, ARBs), vasodilators, and lactulose 1
• Review all medications including over-the-counter drugs that may contribute to hyponatremia or worsen AKI 1
• Assess for infection as a trigger, which is present in 25-40% of AKI cases and requires specific treatment 2, 3
• Monitor serum creatinine daily to assess AKI stage and response to interventions 1

Volume Status Assessment and Etiology Determination

Determining volume status is essential because management differs fundamentally based on whether hyponatremia is hypovolemic, euvolemic, or hypervolemic:

Hypovolemic Hyponatremia

• Administer isotonic crystalloids (preferentially lactated Ringer's) or 5% albumin for volume resuscitation 1
• In cirrhotic patients specifically, albumin at 1 g/kg bodyweight (maximum 100 g/day) for 2 consecutive days is the preferred volume expander 1
• Expect serum creatinine reduction to within 0.3 mg/dL of baseline if truly hypovolemic 1

Hypervolemic Hyponatremia (Most Common in AKI with Cirrhosis)

• Implement fluid restriction to 1,000 mL/day for moderate hyponatremia (120-125 mEq/L) 1
• For severe hyponatremia (<120 mEq/L), use more severe fluid restriction combined with hyperoncotic albumin infusion 1
• Consider vasopressin receptor antagonists (vaptans) in refractory cases, though evidence is limited 1
• Critical pitfall: Do not assume peripheral edema or ascites means adequate renal perfusion—effective circulating volume may still be depleted 2, 3

Euvolemic Hyponatremia

• Manage based on specific underlying cause (SIADH, hypothyroidism, adrenal insufficiency) 4
• Fluid restriction remains the mainstay of treatment 4

Sodium Correction Rate Targets

The rate of sodium correction is critical to prevent osmotic demyelination syndrome (ODS):

• Target sodium correction rate of 4-8 mEq/L per day, not exceeding 10-12 mEq/L in any 24-hour period 1
• In acute hyponatremia (onset <48 hours), more rapid correction is acceptable and necessary to prevent cerebral edema 1
• In chronic hyponatremia (>48 hours), gradual correction is mandatory to avoid ODS 1

Risk factors for ODS include:

• Advanced liver disease, alcoholism, severe hyponatremia, malnutrition, severe metabolic derangements (hypophosphatemia, hypokalemia, hypoglycemia), low cholesterol, and prior encephalopathy 1

Special Considerations for Cirrhotic Patients with AKI

In cirrhotic patients with ascites and AKI, a specific diagnostic and therapeutic algorithm applies:

Diagnostic Workup

• Perform diagnostic paracentesis to exclude spontaneous bacterial peritonitis (SBP), the most common cause of hepatorenal syndrome-AKI (HRS-AKI) 1, 3
• Obtain urinalysis to detect hematuria, proteinuria, or abnormal sediment suggesting structural kidney disease 1
• Check urine sodium (typically <10 mEq/L in HRS) and fractional excretion of sodium (FENa <1% suggests prerenal causes including HRS) 1
• Important caveat: FENa has 100% sensitivity but only 14% specificity for prerenal causes in cirrhosis, so interpret cautiously 1

Treatment Protocol

• If SBP is diagnosed, administer antibiotics plus albumin infusion according to current guidelines 1, 3
• After diuretic withdrawal and albumin challenge, reassess at 48 hours:
  • If creatinine improves to within 0.3 mg/dL of baseline: hypovolemic AKI (prerenal azotemia) 1
  • If no response: consider HRS-AKI or acute tubular necrosis (ATN) 1, 3
• Do not use eGFR equations in cirrhotic patients—they are inaccurate; use absolute creatinine values and ICA-AKI staging criteria 2, 3

Albumin Administration Benefits

• Albumin infusion is associated with improvement in hyponatremia in hospitalized cirrhotic patients 1
• Patients may derive most benefit when serum albumin is kept above 4 g/dL 1
• Monitor carefully for volume overload and life-threatening pulmonary edema 1

Management When Renal Replacement Therapy is Required

When AKI necessitates dialysis in the setting of severe hyponatremia, specialized approaches are required to prevent overcorrection:

Continuous Renal Replacement Therapy (CRRT) Approach

• CRRT is preferred over intermittent hemodialysis for severe hyponatremia with AKI because it allows more controlled sodium correction 5, 6, 7
• Modify replacement fluids and dialysate to create hypotonic solutions with progressively higher sodium concentrations 5, 6, 7
• Calculate target sodium concentration in dialysate/replacement fluid based on desired daily correction rate (4-8 mEq/L/day) 7
• Adjust fluid sodium concentration daily as serum sodium improves 5, 7
• Monitor serum sodium hourly initially, then every 4-6 hours once stable 5, 8

Intermittent Hemodialysis Modifications (if CRRT unavailable)

• Use low dialysate sodium concentration (customized below standard 140 mEq/L) 8
• Prescribe concurrent low dialysate flow rate 8
• Use small surface area dialyzer and low blood flow rate 8
• Infuse dextrose 5% water into venous return line, adjusting rate based on hourly sodium measurements 8

Electrolyte Monitoring During RRT

• Closely monitor potassium, phosphate, and magnesium, as intensive/prolonged KRT causes deficiencies 1
• Hypophosphatemia occurs in 60-80% of ICU patients on KRT 1
• Hypokalemia occurs in approximately 25% of patients on prolonged KRT 1
• Use dialysis solutions containing potassium, phosphate, and magnesium to prevent electrolyte disorders 1

Monitoring Parameters

Implement systematic monitoring to detect complications and assess response:

• Serum sodium: Hourly initially when correcting severe hyponatremia, then every 4-6 hours 5, 8
• Serum creatinine: Daily to assess AKI stage and response 1, 2
• Urine output: Hourly in severe cases via bladder catheterization 2
• Volume status: Repeated clinical assessments, not single evaluation, as both physiological response and underlying condition are dynamic 2
• Neurological status: Monitor for symptoms of hyponatremic encephalopathy (confusion, seizures) or ODS (dysarthria, dysphagia, oculomotor dysfunction, quadriparesis developing 2-7 days after correction) 1
• Electrolytes: Potassium, phosphate, magnesium, especially if on RRT 1

Common Pitfalls to Avoid

• Do not delay treatment waiting for creatinine to reach arbitrary thresholds—intervene early based on AKI staging criteria 2
• Do not assume clinical hypervolemia (edema, ascites) means adequate renal perfusion 2, 3
• Do not use diuretics to treat AKI except for volume overload management 1
• Do not use low-dose dopamine, fenoldopam, or atrial natriuretic peptide—they are ineffective 1
• Avoid starch-containing fluids for volume expansion—they cause harm 1
• Do not overlook infection as an AKI trigger requiring specific treatment 2, 3
• In cirrhotic patients, do not delay albumin trial while waiting for higher creatinine values—old HRS criteria requiring creatinine >2.5 mg/dL have been abandoned 3