Nephrogenic diabetes insipidus
|Nephrogenic diabetes insipidus|
|Classification and external resources|
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 (ADH)/Arginine Vasopressin (AVP). 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.
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 (an excretion of over 2.5 liters of urine per day), 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 entirely separate conditions with a separate pathogenesis. Both cause polyuria (hence the similarity in name) but whereas diabetes insipidus is a problem with the production of antidiuretic hormone (Cranial diabetes insipidus) or renal response to antidiuretic hormone (nephrogenic diabetes insipidus), diabetes mellitus causes polyuria via osmotic diuresis, due to the high blood sugar leaking into the urine, taking excess water along with it.
Nephrogenic DI (NDI) 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.
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 (ADH Resistance) in a mechanism that is not yet fully understood.
Other causes of acquired NDI include: hypokalemia, post-obstructive polyuria, sickle cell disease/trait, amyloidosis, Sjogren syndrome, renal cystic disease, Bartter syndrome and various drugs (Amphotericin B, Orlistat, Ifosfomide, Ofloxacin, Cidofovir, Vaptanes).
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 drugs is lithium, although there are numerous other medications that cause this effect with lesser frequency.
This form of DI can also be hereditary:
|NDI1||304800||AVPR2||Usually, the hereditary form of nephrogenic DI is the result of an X-linked genetic defect which causes the vasopressin receptor (also called the V2 receptor) in the kidney to not function correctly.|
|NDI2||125800||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 |
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.
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.
Persons with nephrogenic diabetes insipidus will need to consume enough fluids to equal the amount of urine produced. Correct any underlying cause such as hypercalcemia. 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 (i.e. dilute urine). This condition results in a high serum osmolarity (all the retained solutes stay in 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. 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.
- Wildin, Robert (2006). "What is NDI?". The Diabetes Inspidus Foundation. http://www.diabetesinsipidus.org/4_types_nephrogenic_di.htm
- Marples D, Frøkiaer J, Dørup J, Knepper MA, Nielsen S (April 1996). "Hypokalemia-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla and cortex". J. Clin. Invest. 97 (8): 1960–8. doi:10.1172/JCI118628. PMC 507266. PMID 8621781.
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- Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS, NEPHROGENIC, X-LINKED -304800
- Online 'Mendelian Inheritance in Man' (OMIM) DIABETES INSIPIDUS, NEPHROGENIC, AUTOSOMAL -125800
- Kavanagh, Sean (20 Jun 2007). "Nephrogenic Diabetes Insipidus". Patient UK. Retrieved 22 Jun 2009.
- Kirchlechner V, Koller DY, Seidl R, Waldhauser F (June 1999). "Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride". Arch. Dis. Child. 80 (6): 548–52. doi:10.1136/adc.80.6.548. PMC 1717946. PMID 10332005.