Nephron vs. Neuron: Diagnosis and management of diabetes insipidus in the critically ill

A 50-year-old man with no significant medical history was admitted to the medical floor with intermittent nausea, vomiting and fever. His hospital course was complicated by tachypnea, fever, and encephalopathy requiring intubation and transfer to the intensive care unit. He rapidly declined neurologically with loss of gag, pupillary, and corneal reflexes. His GCS remained 3T without sedation. CT and MRI of the brain were negative. LP was unremarkable. The nurse calls you for high urine output totaling 3 liters in the last 5 hours. Stat BMP revealed Na 179, K2.7, Cl >140, HCO3 19 and Cr 1.01. Serum osmolality is 372. Urine studies are pending. What is the most likely cause of his increased urine output?


Diabetes Insipidus

Diabetes insipidus (DI) manifests when the kidney fails to reabsorb water due to an abnormality in the amount or response to antidiuretic hormone, causing polyuria, polydipsia, and increased volume of hypoosmolar urine. Hypernatremia causes free water to shift from the intracellular space to the extracellular space. If untreated, DI can rapidly cause severe free water loss, hypovolemia and hypoperfusion. DI can be acquired (most common) or congenital and is further classified into central (neurogenic) and nephrogenic. The table below reviews causes, findings, and management to help differentiate between central and nephrogenic DI. These causes of DI must be differentiated from primary polydipsia or dipsogenic DI, which is most commonly seen in psychiatric patients with excessive water intake while ADH function is preserved. 



Central DI

Nephrogenic DI


Deficiency of antidiuretic hormone (ADH)

Renal resistance to ADH 


Primary tumors, metastases, meningitis/encephalitis or other CNS infections, trauma, surgery, idiopathic, congenital causes

Primary renal disease, obstructive uropathy, metabolic (hypokalemia, hypercalcemia), sick cell disease, drugs (lithium)


Excessive thirst, polydipsia, polyuria (UOP >300 ml/hr for at least 2 hrs), weakness, myalgias, other nonspecific symptoms


Urine osm < 300 mOsm/kg H2O, serum osm > 300 mOsm/kg, hypernatremia


Desmopressin (DDAVP)

Intravascular volume expansion (crystalloid) followed by free water replacement 

*Na correction limited to 8-10 mmol/L per 24 hrs, if hypernatremia present for > 48 hrs

Thiazide diuretics, amiloride (for lithium nephrotoxicity), NSAIDs, reduce dietary protein and sodium


DI in the Critically Ill

In the critical care setting, central DI, rather than nephrogenic, is most commonly seen. Patients at risk of developing DI are those who undergo pituitary surgery and who suffer from traumatic brain injuries, intracranial hypertension, or brain death. Patients experience significant urine output in the setting of reduced intake while in the ICU, which can cause intravascular depletion, hypotension, and hypernatremia. Other causes of polyuria in the ICU include diuretics, postobstructive diuresis and the recovery phase (or de-resuscitative phase) of critical illness. DI can also rarely be observed in critically ill patients after withdrawal of vasopressor support for patients in shock supported with a vasopressin infusion. The proposed mechanism is downregulation of V2 receptors in the distal convoluted tubule and collecting duct, leading to transient nephrogenic DI.  


Key signs and symptoms include:

  • Increased serum osmolality (severe symptoms at >330 mOsm/kg)
  • Hypernatremia (severe symptoms at >150-155 mmol/L)
  • Polyuria (>3L/24h)
  • Hypotonic urine (urine osmolality < 200 mOsm/kg)
  • Lethargy to coma, cerebral edema on imaging, seizures
    • Cerebral shrinkage in hypernatremic/hyperosmolality state leads to vascular rupture and subsequent edema with permanent neurologic damage


  • Send BMP, urine electrolytes, urine osm, serum osm
  • Water deprivation test and DDAVP challenge  (not usually performed in the acute setting, see here for details)


  • Control polyuria
    • Desmopressin (DDAVP) 1 mcg IV initial dose, followed by second injection after 2 hrs, if UOP remains > 1-2 mL/kg/hr 
    • Nephrology or endocrine consultation
  • Manage hypernatremia, dehydration
    • TBW deficit (L) = body weight (kg) x 0.6 x (Na-140)/Na
    • Use isotonic fluids for volume repletion 
    • Can consider normal saline to slow rate of sodium reduction
    • Be aware of rapid reduction, no more than 0.5 mmol/L/hr to avoid cerebral edema/demyelination
    • Monitor BMP every 4 hours
    • Consider hemodialysis
  • Monitor neurologic status
    • MRI Brain with and without contrast to assess for cerebral edema, possible herniation, and/or brain death


  • Hypernatremia is an independent risk factor for mortality in critically patients 
  • Mortality positively correlates with degree of hypernatremia


Harrois A and Anstey JR. Diabetes Insipidus and SIADH in Critically Ill Patients. Crit Care Clinics 2019;35:187-200. 


Lindner, G., & Funk, G. C. Hypernatremia in critically ill patients. Journal of critical care 2013;28(2):216.e11–216.e2.16E20.


Robertson, G. L. Diabetes insipidus: differential diagnosis and management. Best Practice & Research Clinical Endocrinology & Metabolism 2016;30(2):205-218.