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Morning ReportPediatric Nephrology Service
May 24, 2004
Sapna Sutaria, M.D. (PL3)
Diabetes Insipidus
Background
Diabetes insipidus (DI) is a disease characterized by polyuria and polydipsia
Central DI: results from a lack of circulating arginine vasopressin (ADH) due to an abnormality in either synthesis or secretion
Nephrogenic DI: results from a failure of AVP-sensitive epithelial cells of the kidney collecting duct to respond normally to ADH
Normal Physiology
Vasopressin in synthesized by the supraoptic and paraventricular nuclei of the hypothalamus
It is then transported to the posterior pituitary where stored until its release
Vasopressin release from posterior pituitary is primarily regulated by changes in plasma osmolality
The primary site of vasopressin action in the kidney is at the collecting duct
Vasopressin receptors are classified as V1 and V2
Etiologies of Central DI
Primary inherited forms—rare – Autosomal Dominant form– Wolfram syndrome– septo-optic dysplasia
Etiologies of Central DI
Secondary or acquired causes—more common– tumors of the suprasellular and chiasmatic regions
(craniopharyngiomas, optic gliomas, germinomas)– Head injury (basal skull fx)– Operations (near pituitary or hypothalamus)– Systemic diseases (encephalitis, histiocytosis,
turberculosis, leukemia)– Autoantibodies to vasopressin-producing cells
Etiologies of Central DI
In the newborn, DI has been reported in association with asphyxia, IVH, intravascular coagulopathy, Listeria monocytogenes sepsis, and GBBS meningitis
Approx 20% of cases of DI are idiopathic
Etiologies of Nephrogenic DI
Primary inherited causes– Mutations that affect the V2 receptor as well as
the AQP 2 water channel– The V2 receptor gene is localized the the X
chromosome– V2 receptor mutations may also appear de novo– Inherited autosomal recessive forms of
nephrogenic DI also reported (mutation localized to chromosome 12)
Etiologies of Nephrogenic DI
Secondary or acquired forms– More common than primary forms– Drugs (lithium, ampho B, demeclocycline)– Can be associated with prolonged intervals of
hypercalcemia or hypokalemia– Can be present in conjunction with inherited
disorders of renal development (Polycystic kidney disease, renal dysplasia)
– Disease processes that injure the collecting duct & surrounding tubules (sickle cell anemia, chronic pyelonephritis, urinary tract obstruction)
Patient History
How much pt drinks per day Voiding patterns Dietary intake Drugs/meds
Clinical Manifestations
POLYURIA POLYDIPSIA Signs and symptoms of chronic dehydration Infants: irritability, poor feeding, growth failure,
intermittent high fevers In children who have acquired bladder control,
enuresis may be the first symptom
Clinical Manifestations
Central DI– Hypothalamic tumors: growth disturbances,
progressive cachexia or obesity, hyperpyrexia, sleep disturbance, sexual precocity, or emotional disorders
– Lesions initially causing DI may eventually destroy the anterior pituitary and its associated endocrine axes
Labs
Urine is usually pale and colorless UA and urine electrolytes Urine SG varies b/w 1.001 and 1.010 Uosm usually 50-300 mOsm/kg Sosm may vary widely, depending on
hydration status Other renal fxn studies usually nl Serum AVP measurement
Imaging
Imaging– RUS– MRI
Tumors—calcifications; enlargement of sella turcica; increased width of suture lines
“Bright spot”—differentiates between posterior pituitary and anterior pituitary; present in normal pts; absent or ectopic in pts with hypothalamic-neurohypophyseal tract lesions
Diagnosis
Administration of DDAVP– In central DI, DDAVP will raise Uosm and
suppress UOP– In nephrogenic DI, DDAVP produces no
increase in Uosm and no suppression of UOP– In normal individuals, DDAVP administration
can cause a vasodilatory response (flushing, fall in diastolic BP, rise in HR), believed to be mediated by extrarenal V2 receptors
Diagnosis
Water deprivation test– In pts with severe DI, a 3 hr interval of
water deprivation may result in elevation of Sosm, whereas Uosm remains at less that plasma values
Treatment
The cause of the underlying condition should be treated when possible
Treatment
Central DI– Administration of DDAVP, usually intranasally– DDAVP binds almost exclusively to V2 receptors
and is more resistant to degradation by body peptidases than endogenous vasopressin
– Therefore, the antidiuretic effects of DDAVP last 8-10 hr, compared with 1-3 hr for endogenous vasopressin
– Dose: 5-10 mcg IN, given in single or divided doses; < 2 y/o: 0.15-0.5 mcg/kg/24 hr
– IV/SQ therapy also available
Treatment
Nephrogenic DI– Ensure a sufficient intake of water to replace
the large urinary water losses– Stop causative medications, if applicable– Low sodium diet– Drugs that reduce polyuria
Thiazide diuretics (hydrochlorothiazide) Prostaglandin synthesis inhibitors (indomethacin) Potassium-sparing diuretics (amiloride)
Management
Check serum electrolytes frequently After episodes of dehydration, these patients
usually require replacement of large quantities of water, but not sodium (**remember this when choosing IV fluids**)
Involve endocrine and nephrology services (and genetics, if indicated, for genetic counseling)
Prognosis
Central DI– Prognosis often determined by the
underlying etiologic process – Central DI may be transient or long-standing– Uncomplicated central DI can be managed
effectively; permits a high quality of life for affected patients
Prognosis
Nephrogenic DI– Good prognosis, if careful clinical and
laboratory monitoring– There are isolated reports of CRF in pts
with nephrogenic DI
The End