Nephrogenic diabetes insipidus
Encyclopedia
Nephrogenic diabetes insipidus is a form of diabetes insipidus
due primarily to pathology of the kidney
. This is in contrast to central/neurogenic diabetes insipidus
, which is caused by insufficient levels of antidiuretic hormone (ADH)/Argenine 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.
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.
, polycystic kidney disease
, electrolyte imbalance, or some other kidney defect.
The major causes of acquired NDI that produce clinical symptoms (e.g. polyuria) in the adult are lithium toxicity and hypercalcemia.
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.
Hypercalcemia causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium sensing receptor (CaR).
Osmotic
Other causes of acquired NDI include: hypokalemia, post-obstructive polyuria, sickle cell disease/trait, amyloidosis, Sjogren syndrome, renal cystic disease, Barter 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 medication
s. The most common and well known of these drugs is lithium
, although there are numerous other medications that cause this effect with lesser frequency.
, 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, but still is unable to concentrate the urine - hypernatremia will ensue with its neurologic symptoms.
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.
and amiloride
. Consider a low-salt and low-protein diet.
In nephrogenic Diabetes Inspidus caused by Lithium (seen in Bipolar patients for example), K-sparing diuretics such as Amiloride
would be used. The goal in this case is to excrete Lithium. Using Hydrochlorothiazide in this case would increase aldosterone, which would lead to increased Sodium retention (and Lithium as well).
Diabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
due primarily to pathology of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
. This is in contrast to central/neurogenic diabetes insipidus
Neurogenic diabetes insipidus
Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain...
, which is caused by insufficient levels of antidiuretic hormone (ADH)/Argenine 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.
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 (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
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
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.
Acquired
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 amyloidosisAmyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
, polycystic kidney disease
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
, electrolyte imbalance, or some other kidney defect.
The major causes of acquired NDI that produce clinical symptoms (e.g. polyuria) in the adult are lithium toxicity and hypercalcemia.
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.
Hypercalcemia causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium sensing receptor (CaR).
Osmotic
Other causes of acquired NDI include: hypokalemia, post-obstructive polyuria, sickle cell disease/trait, amyloidosis, Sjogren syndrome, renal cystic disease, Barter 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 medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
s. The most common and well known of these drugs is lithium
Lithium pharmacology
Lithium pharmacology refers to use of the lithium ion, Li+, as a drug. A number of chemical salts of lithium are used medically as a mood stabilizing drug, primarily in the treatment of bipolar disorder, where they have a role in the treatment of depression and particularly of mania, both acutely...
, although there are numerous other medications that cause this effect with lesser frequency.
Hereditary
This form of DI can also be hereditary:| 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 Vasopressin receptor A vasopressin receptor is a cell surface receptor which binds vasopressin. The three types of vasopressin receptor are members of the A6 subfamily of G-protein coupled receptors.-Subtypes:Humans express three subtypes: 1A, 1B and 2-Function:... (also called the V2 receptor) in the kidney to not function correctly. |
|
| NDI2 | AQP2 | In more rare cases, a mutation in the "aquaporin 2 Aquaporin 2 AQP2 is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell.-Regulation:It is the only aquaporin regulated by vasopressin.... " 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 |
Presentation
The clinical manifestation is similar to neurogenic diabetes insipidusNeurogenic diabetes insipidus
Neurogenic diabetes insipidus, more commonly known as central diabetes insipidus, is due to a lack of vasopressin production in the brain...
, 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, but still is unable to concentrate the urine - hypernatremia will ensue with its neurologic symptoms.
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
Desmopressin
Desmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...
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
Treat any underlying cause, allow the patient to drink as much as required. Correct metabolic abnormalities. The first line of treatment is hydrochlorothiazideHydrochlorothiazide
Hydrochlorothiazide, abbreviated HCTZ, HCT, or HZT, is a first-line diuretic drug of the thiazide class that acts by inhibiting the kidneys' ability to retain water. This reduces the volume of the blood, decreasing blood return to the heart and thus cardiac output and, by other mechanisms, is...
and amiloride
Amiloride
Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...
. Consider a low-salt and low-protein diet.
In nephrogenic Diabetes Inspidus caused by Lithium (seen in Bipolar patients for example), K-sparing diuretics such as Amiloride
Amiloride
Amiloride is a potassium-sparing diuretic, first approved for use in 1967 , used in the management of hypertension and congestive heart failure. Amiloride was also tested as treatment of cystic fibrosis, but it was revealed inefficient in vivo due to it's short time of action, therefore...
would be used. The goal in this case is to excrete Lithium. Using Hydrochlorothiazide in this case would increase aldosterone, which would lead to increased Sodium retention (and Lithium as well).