What is the significance of low urine specific gravity and hypernatremia in an obese patient on lisinopril (Angiotensin-Converting Enzyme inhibitor, ACE inhibitor) and lithium, presenting with urinary frequency and polyuria, despite normal HbA1c levels?

Lithium-Induced Nephrogenic Diabetes Insipidus with Hypernatremia

The combination of low urine specific gravity (1.005) with hypernatremia (149) in a patient on lithium therapy who has polyuria strongly indicates lithium-induced nephrogenic diabetes insipidus (NDI), which requires immediate discontinuation of lithium and consultation with nephrology and psychiatry.

Diagnosis and Clinical Significance

The clinical presentation shows classic features of nephrogenic diabetes insipidus:

• Extremely dilute urine (specific gravity 1.005) despite hypernatremia (149 mmol/L)
• Polyuria and urinary frequency
• Normal HbA1c (5.4%) ruling out osmotic diuresis from diabetes mellitus
• Current lithium therapy, a well-established cause of NDI

Pathophysiology

Lithium-induced NDI occurs through several mechanisms:

• Inhibition of vasopressin (ADH) action in the collecting ducts
• Downregulation of aquaporin-2 water channels
• Reduced urinary concentrating ability 1

The patient's ability to concentrate urine is severely impaired, leading to:

• Excessive free water loss
• Hypernatremia (149 mmol/L)
• Compensatory polydipsia

Risk Factors and Complications

Several factors in this patient increase the risk and severity of NDI:

1. Lithium therapy - The primary cause of NDI in this case 2
2. Lisinopril (ACE inhibitor) - May worsen renal function in combination with lithium 3
3. Obesity - Associated with salt sensitivity and increased sodium retention 4

Complications of untreated NDI with hypernatremia include:

• Dehydration
• Electrolyte imbalances
• Increased risk of thromboembolism 1
• Neurological symptoms (confusion, seizures)
• Potential for acute kidney injury

Management Algorithm

Immediate Management:

1. Discontinue lithium - The most important intervention to prevent further renal damage 2
2. Nephrology and psychiatry consultation - For coordinated management
3. Hypotonic fluid administration - To correct hypernatremia at a controlled rate (not exceeding 8-10 mEq/L/day)
4. Consider temporary discontinuation of lisinopril - May contribute to renal dysfunction 3, 5

Diagnostic Workup:

1. Water deprivation test - To confirm NDI diagnosis if diagnosis remains unclear
2. Measure serum lithium level - To assess for toxicity
3. Comprehensive renal function assessment - Including GFR, electrolytes, and urine studies
4. Evaluate for other causes of polyuria - Though diabetes mellitus is unlikely with normal HbA1c

Long-term Management:

1. Alternative psychiatric medication - Replace lithium with another mood stabilizer in consultation with psychiatry
2. Thiazide diuretics - Paradoxically reduce polyuria in NDI by promoting proximal tubular water reabsorption 4
3. Low-sodium diet - To reduce osmotic load and water requirement
4. Regular monitoring of renal function - GFR and electrolytes
5. Adequate fluid intake - To prevent dehydration but avoid overhydration

Special Considerations

• Medication interactions: The combination of lithium and ACE inhibitors (lisinopril) increases the risk of renal dysfunction 3
• Chronic lithium use: After 15+ years of lithium therapy, up to 21% of patients have reduced GFR and 44% have reduced urinary concentrating capacity 2
• Reversibility: Early NDI may partially resolve after lithium discontinuation, but long-standing cases may have permanent renal damage

Common Pitfalls to Avoid

1. Misdiagnosing as uncontrolled diabetes mellitus - The normal HbA1c rules this out 6
2. Aggressive fluid restriction - Contraindicated in NDI as it may worsen hypernatremia
3. Rapid correction of hypernatremia - Can lead to cerebral edema and neurological damage
4. Continuing lithium - Will lead to progressive renal damage 2
5. Failure to recognize the seriousness - Severe hypernatremia has high mortality and requires urgent intervention

The management of this patient requires a coordinated approach between nephrology and psychiatry to address both the renal complications and the underlying psychiatric condition requiring lithium therapy.