Nephrogenic Diabetes Insipidus
The most likely diagnosis is nephrogenic diabetes insipidus (NDI), characterized by renal resistance to antidiuretic hormone, which explains the combination of polyuria, polydipsia, hypernatremia (serum sodium 149 mEq/L), and inappropriately dilute urine (specific gravity <1.005, corresponding to urine osmolality <300 mOsm/kg). 1, 2
Diagnostic Reasoning
The clinical presentation is pathognomonic for diabetes insipidus based on the following key features:
Inappropriately dilute urine in the setting of hypernatremia: A urine specific gravity <1.005 (equivalent to urine osmolality <300 mOsm/kg) with serum sodium of 149 mEq/L indicates complete failure of urinary concentration despite adequate—indeed excessive—physiologic stimulus for antidiuretic hormone release. 1, 2
Exclusion of diabetes mellitus: This eliminates osmotic diuresis from hyperglycemia as the cause of polyuria. 2
Pattern consistent with NDI rather than central DI: While both forms of diabetes insipidus present with hypotonic polyuria, NDI is characterized by resistance to arginine vasopressin (AVP) action at the kidney level, whereas central diabetes insipidus results from AVP deficiency. 1, 3
The diagnostic criteria for NDI include inappropriately low urine osmolality (<500 mOsm/kg) in the presence of elevated plasma osmolality, which this patient clearly demonstrates. 1, 2
Distinguishing NDI from Central DI
While the initial presentation is identical, further testing would differentiate these conditions:
Baseline plasma copeptin >21.4 pmol/L is diagnostic for NDI in adults, as copeptin (a surrogate marker for AVP) would be elevated in NDI due to intact hypothalamic-pituitary function but renal resistance. 1, 2
Water deprivation test followed by desmopressin administration remains the gold standard: NDI patients show no significant increase in urine osmolality after desmopressin, whereas central DI patients demonstrate marked improvement. 4, 5
Etiology Considerations
NDI can be:
Congenital: Due to genetic mutations affecting the vasopressin V2 receptor or aquaporin-2 water channels. 6
Acquired: Secondary to medications (lithium, demeclocycline), electrolyte disorders (hypercalcemia, hypokalemia), or chronic kidney disease. 1
Genetic testing is recommended as first-line for suspected congenital NDI, especially with family history. 1
Immediate Management Priorities
Free access to water is the cornerstone of NDI management to prevent life-threatening dehydration, worsening hypernatremia, and associated complications. 6, 1, 7
Pharmacological Treatment
Thiazide diuretics are first-line treatment for symptomatic NDI: They induce mild volume depletion, paradoxically increasing proximal tubular sodium and water reabsorption, thereby reducing urine output by 30-50%. 1, 7
Amiloride should be added if thiazides cause hypokalemia, which is common and can worsen the concentrating defect. 6
Prostaglandin synthesis inhibitors (NSAIDs) can be considered in symptomatic patients, particularly in early childhood, though gastric acid inhibitors should be used concurrently with nonselective cyclooxygenase inhibitors. 6
Dietary Modifications
Low sodium diet (reduced renal solute load) enhances the effect of thiazide diuretics and reduces obligatory water excretion. 1, 7
Moderate protein restriction decreases renal solute load and subsequent obligatory water excretion. 1, 7
Avoid excessive salt supplementation: Unlike Bartter syndrome, salt supplementation in NDI would worsen polyuria and risk hypernatremic dehydration. 6
Critical Monitoring
Electrolytes (sodium, potassium, chloride, bicarbonate) and renal function: Every 2-3 months initially, then every 3-12 months once stable. 7
Kidney ultrasound at least every 2 years to monitor for urinary tract dilatation or bladder dysfunction from chronic polyuria ("flow uropathy"). 6, 7
Weight and fluid balance monitoring, especially during intercurrent illness when oral intake may be compromised. 7
Important Caveats
NDI patients are at high risk for chronic kidney disease: Approximately 50% of adult NDI patients develop CKD stage ≥2, requiring long-term nephrology follow-up. 7
Hypernatremic dehydration can develop rapidly if water access is restricted (during procedures, hospitalization, or illness with vomiting). 6, 7
Treatment efficacy should be evaluated via urine osmolality, urine output, and clinical symptoms rather than attempting complete normalization of all parameters, which is often unattainable. 6