Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus is a form of diabetes insipidus primarily due to pathology of the kidney. This is in contrast to central or neurogenic diabetes insipidus, which is caused by insufficient levels of antidiuretic hormone. 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.
Signs and symptoms
The clinical manifestation is similar to neurogenic diabetes insipidus, presenting with polydipsia and polyuria. 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 abnormal 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: hypokalemia, post-obstructive polyuria, sickle cell disease or trait, amyloidosis, Sjögren 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 of 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 due to defects in the following genes:| Type | OMIM | Gene | Locus |
| NDI1 | AVPR2 | Usually, the hereditary form of nephrogenic DI is the result of an X-linked genetic defect which causes the vasopressin receptor in the kidney to not function correctly. | |
| NDI2 | AQP2 | In more rare cases, a mutation in the "aquaporin 2" gene impede the normal functionality of the kidney water channel, which results in the kidney being unable to absorb water. This mutation is often inherited in an autosomal recessive manner although dominant mutations are reported from time to time |
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 diabetes insipidus; 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. Patients may also consider a low-salt and low-protein diet.Thiazide diuretics are 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 polydipsia 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 polyuria.
Etymology
The name of the disease comes from:- diabetes: from diabetes, from διαβήτης diabḗtēs "a passer-through; siphon", from Greek διαβαίνειν diabaínein "to pass through", from δια- dia- "through" + βαίνειν baínein "to go".
- insipidus: from Late Latin: insipidus "tasteless," from Latin in- "not" + sapidus "tasty", from sapere "to taste".
Although they share part of their names, 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.