Nephrogenic diabetes insipidus is a form of diabetes insipidus primarily due to
pathology of the kidney. This is in contrast to central/neurogenic diabetes
insipidus, which is caused by insufficient levels of antidiuretic
hormone/Arginine Vasopressin. Nephrogenic diabetes insipidus is caused
by an improper response of the kidney to ADH, leading to a decrease in the
ability of the kidney to concentrate the urine by removing free water.
Etymology The name of the disease comes from:
Diabetes - from L. diabetes, from Gk. diabetes "excessive discharge of urine,"
lit. "a passer-through, siphon," from diabainein "to pass through," from dia-
"through" + bainein "to go" Insipidus - "without taste or
perceptible flavor," from Fr. insipide, from L.L. inspidus "tasteless," from L.
in- "not" + sapidus "tasty," from sapere "have a taste"
This is because patients experience polyuria, and that the urine content
does not have an elevated glucose concentration, as opposed to diabetes
mellitus. Although they shared a name, diabetes
mellitus and diabetes insipidus are two separate conditions. Both cause
excessive urination but whereas diabetes insipidus is a problem with the
production of antidiuretic hormone or the kidneys' response to antidiuretic
hormone, diabetes mellitus causes polyuria via osmotic diuresis, due to
the high blood sugar leaking into the urine, taking excess water along with
it. Signs and symptoms
The clinical manifestation is similar to neurogenic diabetes insipidus,
presenting with excessive thirst and excretion of a large amount of dilute
urine. Dehydration is common, and incontinence can occur secondary to
chronic bladder distension. On investigation, there will be an
increased plasma osmolarity and decreased urine osmolarity. As pituitary
function is normal, ADH levels are likely to be a normal or raised.
Polyuria will continue as long as the patient is able to drink. If the patient
is unable to drink and is still unable to concentrate the urine, then
hypernatremia will ensue with its neurologic symptoms.
Causes = Acquired=
Nephrogenic DI is most common in its acquired forms, meaning that the defect
was not present at birth. These acquired forms have numerous potential causes.
The most obvious cause is a kidney or systemic disorder, including
amyloidosis, polycystic kidney disease, electrolyte imbalance, or some other
kidney defect. The major causes of acquired NDI that
produce clinical symptoms in the adult are lithium toxicity and high blood
calcium. Chronic lithium ingestion - appears to
affect the tubules by entering the collecting tubule cells through sodium
channels, accumulating and interfering with the normal response to ADH in a
mechanism that is not yet fully understood.
High blood calcium causes natriuresis and water diuresis, in part by its
effect through the calcium-sensing receptor.
Osmotic Other causes of acquired NDI include:
low blood potassium, post-obstructive polyuria, sickle cell disease/trait,
amyloidosis, Sjogren syndrome, renal cystic disease, Bartter syndrome, and
various medications. In addition to kidney and systemic
disorders, nephrogenic DI can present itself as a side-effect to some
medications. The most common and well known of these medications is lithium,
although there are many other medications that cause this effect with
lesser frequency. = Hereditary=
This form of DI can also be hereditary: Diagnosis
Differential diagnosis includes nephrogenic diabetes insipidus,
neurogenic/central diabetes insipidus and psychogenic polydipsia. They may be
differentiated by using the water deprivation test. Recently, lab assays
for ADH are available and can aid in diagnosis.
If able to rehydrate properly, sodium concentration should be nearer to the
maximum of the normal range. This, however, is not a diagnostic finding, as
it depends on patient hydration. DDAVP can also be used; if the patient
is able to concentrate urine following administration of DDAVP, then the cause
of the diabetes insipidus is neurogenic; if no response occurs to DDAVP
administration, then the cause is likely to be nephrogenic.
Treatment Persons with nephrogenic diabetes
insipidus will need to consume enough fluids to equal the amount of urine
produced. Any underlying cause such as high blood calcium must be corrected to
treat NDI. The first line of treatment is hydrochlorothiazide and amiloride.
Consider a low-salt and low-protein diet.
Thiazide is used in treatment because diabetes insipidus causes the excretion
of more water than sodium. This condition results in a net concentrating
effect on the serum. This high serum osmolarity stimulates excessive thirst
in an attempt to dilute the serum back to normal and provide free water for
excreting the excess serum solutes. However, since the patient is unable to
concentrate urine to excrete the excess solutes, the resulting urine fails to
decrease serum osmolarity and the cycle repeats itself, hence excessive
urination. Thiazide diuretics allow increased excretion of Na+ and water,
thereby reducing the serum osmolarity and eliminating volume excess.
Basically, thiazides allow increased solute excretion in the urine, breaking
the polydipsia-polyuria cycle. References