Nephrogenic diabetes insipidus

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Nephrogenic diabetes insipidus
Other namesarginine vasopressin resistance; AVP-R; renal diabetes insipidus
Specialty Nephrology, endocrinology, urology   OOjs UI icon edit-ltr-progressive.svg
Symptoms Polyuria, nocturia, and polydipsia.
Complications Dehydration, seizures
Diagnostic method Urine tests, blood tests, fluid deprivation test
Differential diagnosis AVP-D (central), Diabetes mellitus
TreatmentDrinking sufficient fluids
Medication thiazides, aspirin
Frequency3 per 100,000 per year

Nephrogenic diabetes insipidus, recently renamed arginine vasopressin resistance (AVP-R) and previously known as renal 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 vasopressin (also called antidiuretic hormone, ADH). Nephrogenic diabetes insipidus is caused by an improper response of the kidney to vasopressin, leading to a decrease in the ability of the kidney to concentrate the urine by removing free water.[ citation needed ]

Contents

Signs and symptoms

The clinical manifestation is similar to neurogenic diabetes insipidus, presenting with polydipsia (excessive thirst) and polyuria (excretion of a large amount of dilute urine). Dehydration is common, and incontinence can occur secondary to chronic bladder distension. [1] On investigation, there will be an increased plasma osmolarity and decreased urine osmolarity. As pituitary function is normal, antidiuretic hormone 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.[ citation needed ]

Causes

Acquired

Nephrogenic diabetes insipidus 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, [2] polycystic kidney disease, [3] electrolyte imbalance, [4] [5] or some other kidney defect. [2]

The major causes of acquired nephrogenic diabetes insipidus that produce clinical symptoms (e.g., polyuria) in the adult are lithium toxicity and high blood calcium. About 80% of lithium ingested appears to affect the proximal tubules by entering the collecting tubule cells through sodium channels, accumulating and interfering with the normal response to antidiuretic hormone in a mechanism that is not yet fully understood. [6] High blood calcium causes natriuresis (increased sodium loss in the urine) and water diuresis, in part by its effect through the calcium-sensing receptor.[ citation needed ]

Osmotic

Other causes of acquired nephrogenic diabetes insipidus include hypokalemia (low blood potassium), post-obstructive polyuria, sickle cell disease or trait, amyloidosis, Sjögren syndrome, renal cystic disease, Bartter syndrome, and various medications (amphotericin B, orlistat, ifosfamide, ofloxacin, cidofovir, vaptans).[ citation needed ]

In addition to kidney and systemic disorders, nephrogenic diabetes insipidus can present itself as a side effect of some medications. The most common and well known of these medications is lithium, [7] although there are many other medications that cause this effect with lesser frequency. [2]

Hereditary

This form of diabetes insipidus can also be hereditary due to defects in the following genes:

Type OMIM GeneLocus
NDI1 304800 AVPR2 Usually, the hereditary form of nephrogenic diabetes insipidus 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. [2] [8]
NDI2 125800 AQP2 In more rare cases, a mutation in the "aquaporin 2" gene impedes 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 [2] [9]

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 antidiuretic hormone are available and can aid in diagnosis. If the patient is 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.[ citation needed ]

Desmopressin can also be used; if the patient is able to concentrate urine following administration of desmopressin, then the cause of the diabetes insipidus is neurogenic diabetes insipidus; if no response occurs to desmopressin, then the cause is likely to be nephrogenic.[ citation needed ]

Treatment

Persons with nephrogenic diabetes insipidus must consume enough fluids to equal the amount of urine produced. Any underlying cause such as high blood calcium must be corrected to treat nephrogenic diabetes insipidus. The first line of treatment is hydrochlorothiazide and amiloride. [10] Patients may also consider a low-salt and low-protein diet.[ citation needed ]

Thiazide diuretics cause a mild decrease in extracellular fluid volume through natriuresis and diuresis which in turn increases the proximal absorption of sodium and water, lowering urine output. [11]

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.[ citation needed ]

Etymology

The name of the disease comes from:

This is because patients experience polyuria (an excretion of over 2.5 liters of urine per day), and the urine does not have an elevated glucose concentration, as opposed to diabetes mellitus. The two diseases were named (in ancient times) for the fact that one features polyuria in which the urine tastes sweet, whereas the other features polyuria in which the urine tastes unremarkable.[ citation needed ]

Although they share part of their names, diabetes mellitus and diabetes insipidus are two separate conditions. Both cause excessive urination (hence the similarity in name), but whereas diabetes insipidus is a problem with the production of antidiuretic hormone (neurogenic diabetes insipidus) or the kidneys' 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.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Diabetes insipidus</span> Condition characterized by large amounts of dilute urine and increased thirst

Diabetes insipidus (DI), alternately called arginine vasopressin deficiency (AVP-D) or arginine vasopressin resistance (AVP-R), is a condition characterized by large amounts of dilute urine and increased thirst. The amount of urine produced can be nearly 20 liters per day. Reduction of fluid has little effect on the concentration of the urine. Complications may include dehydration or seizures.

<span class="mw-page-title-main">Vasopressin</span> Mammalian hormone released from the pituitary gland

Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then travels down the axon terminating in the posterior pituitary, and is released from vesicles into the circulation in response to extracellular fluid hypertonicity (hyperosmolality). AVP has two primary functions. First, it increases the amount of solute-free water reabsorbed back into the circulation from the filtrate in the kidney tubules of the nephrons. Second, AVP constricts arterioles, which increases peripheral vascular resistance and raises arterial blood pressure.

<span class="mw-page-title-main">Polyuria</span> Excess urination

Polyuria is excessive or an abnormally large production or passage of urine. Increased production and passage of urine may also be termed as diuresis. Polyuria often appears in conjunction with polydipsia, though it is possible to have one without the other, and the latter may be a cause or an effect. Primary polydipsia may lead to polyuria. Polyuria is usually viewed as a symptom or sign of another disorder, but it can be classed as a disorder, at least when its underlying causes are not clear.

Diuresis is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance.

Polydipsia is excessive thirst or excess drinking. The word derives from Greek πολυδίψιος (poludípsios) 'very thirsty', which is derived from Ancient Greek πολύς (polús) 'much, many' and δίψα (dípsa) 'thirst'. Polydipsia is a nonspecific symptom in various medical disorders. It also occurs as an abnormal behaviour in some non-human animals, such as in birds.

<span class="mw-page-title-main">Desmopressin</span> Medication

Desmopressin, sold under the trade name DDAVP among others, is a medication used to treat diabetes insipidus, bedwetting, hemophilia A, von Willebrand disease, and high blood urea levels. In hemophilia A and von Willebrand disease, it should only be used for mild to moderate cases. It may be given in the nose, by injection into a vein, by mouth, or under the tongue.

Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and bleeding in or around the brain. Normal serum sodium levels are 135–145 mmol/L. Hypernatremia is generally defined as a serum sodium level of more than 145 mmol/L. Severe symptoms typically only occur when levels are above 160 mmol/L.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes a physiologically inappropriate increase in solute-free water being reabsorbed by the tubules of the kidney to the venous circulation leading to hypotonic hyponatremia.

Cerebral salt-wasting syndrome (CSWS), also written cerebral salt wasting syndrome, is a rare endocrine condition featuring a low blood sodium concentration and dehydration in response to injury (trauma) or the presence of tumors in or surrounding the brain. In this condition, the kidney is functioning normally but excreting excessive sodium. The condition was initially described in 1950. Its cause and management remain controversial. In the current literature across several fields, including neurology, neurosurgery, nephrology, and critical care medicine, there is controversy over whether CSWS is a distinct condition, or a special form of syndrome of inappropriate antidiuretic hormone secretion (SIADH).

<span class="mw-page-title-main">Demeclocycline</span> Chemical compound

Demeclocycline is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens.

Nocturia is defined by the International Continence Society (ICS) as "the complaint that the individual has to wake at night one or more times for voiding ". The term is derived from Latin nox – "night", and Greek [τα] ούρα – "urine". Causes are varied and can be difficult to discern. Although not every patient needs treatment, most people seek treatment for severe nocturia, waking up to void more than 2 or 3 times per night.

<span class="mw-page-title-main">Primary polydipsia</span> Medical condition

Primary polydipsia and psychogenic polydipsia are forms of polydipsia characterised by excessive fluid intake in the absence of physiological stimuli to drink. Psychogenic polydipsia caused by psychiatric disorders—oftentimes schizophrenia—is frequently accompanied by the sensation of dry mouth. Some conditions with polydipsia as a symptom are non-psychogenic. Primary polydipsia is a diagnosis of exclusion.

<span class="mw-page-title-main">Vasopressin receptor 2</span> Protein-coding gene in the species Homo sapiens

Vasopressin receptor 2 (V2R), or arginine vasopressin receptor 2, is a protein that acts as receptor for vasopressin. AVPR2 belongs to the subfamily of G-protein-coupled receptors. Its activity is mediated by the Gs type of G proteins, which stimulate adenylate cyclase.

<span class="mw-page-title-main">Aquaporin-2</span> Protein-coding gene in the species Homo sapiens

Aquaporin-2 (AQP-2) is found in the apical cell membranes of the kidney's collecting duct principal cells and in intracellular vesicles located throughout the cell. It is encoded by the AQP2 gene.

<span class="mw-page-title-main">Fluid deprivation test</span>

A fluid or water deprivation test is a medical test which can be used to determine whether the patient has diabetes insipidus as opposed to other causes of polydipsia. The patient is required, for a prolonged period, to forgo intake of water completely, to determine the cause of the thirst.

An antidiuretic is a substance that helps to control fluid balance in an animal's body by reducing urination, opposing diuresis. Its effects are opposite that of a diuretic. The major endogenous antidiuretics are antidiuretic hormone and oxytocin. Both of those are also used exogenously as medications in people whose bodies need extra help with fluid balance via suppression of diuresis. In addition, there are various other antidiuretic drugs, some molecularly close to ADH or oxytocin and others not. Antidiuretics reduce urine volume, particularly in diabetes insipidus (DI), which is one of their main indications.

<span class="mw-page-title-main">Nephrocalcinosis</span> Medical condition caused by the deposition of calcium salts in the kidneys

Nephrocalcinosis, once known as Albright's calcinosis after Fuller Albright, is a term originally used to describe the deposition of poorly soluble calcium salts in the renal parenchyma due to hyperparathyroidism. The term nephrocalcinosis is used to describe the deposition of both calcium oxalate and calcium phosphate. It may cause acute kidney injury. It is now more commonly used to describe diffuse, fine, renal parenchymal calcification in radiology. It is caused by multiple different conditions and is determined by progressive kidney dysfunction. These outlines eventually come together to form a dense mass. During its early stages, nephrocalcinosis is visible on x-ray, and appears as a fine granular mottling over the renal outlines. It is most commonly seen as an incidental finding with medullary sponge kidney on an abdominal x-ray. It may be severe enough to cause renal tubular acidosis or even end stage kidney disease, due to disruption of the kidney tissue by the deposited calcium salts.

Central diabetes insipidus, recently renamed arginine vasopressin deficiency (AVP-D), is a form of diabetes insipidus that is due to a lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion.

<span class="mw-page-title-main">Adipsia</span> Medical condition

Adipsia, also known as hypodipsia, is a symptom of inappropriately decreased or absent feelings of thirst. It involves an increased osmolality or concentration of solute in the urine, which stimulates secretion of antidiuretic hormone (ADH) from the hypothalamus to the kidneys. This causes the person to retain water and ultimately become unable to feel thirst. Due to its rarity, the disorder has not been the subject of many research studies.

<span class="mw-page-title-main">Diuretic</span> Substance that promotes the production of urine

A diuretic is any substance that promotes diuresis, the increased production of urine. This includes forced diuresis. A diuretic tablet is sometimes colloquially called a water tablet. There are several categories of diuretics. All diuretics increase the excretion of water from the body, through the kidneys. There exist several classes of diuretic, and each works in a distinct way. Alternatively, an antidiuretic, such as vasopressin, is an agent or drug which reduces the excretion of water in urine.

References

  1. "Diabetes Insipidus. Diabetes symptoms and information". www.patient.co.uk. Retrieved 2018-05-18.
  2. 1 2 3 4 5 Wildin, Robert (2006). "What is NDI?". Nephrogenic Diabetes Insipidus. The Diabetes Inspidus Foundation. Archived from the original on 2009-04-01. Retrieved 2009-04-04.
  3. "Diabetes Insipidus". National Institute of Diabetes and Digestive and Kidney Diseases. Archived from the original on 2011-06-08. Retrieved 2018-05-18.
  4. 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". Journal of Clinical Investigation. 97 (8): 1960–8. doi:10.1172/JCI118628. PMC   507266 . PMID   8621781.
  5. Carney S, Rayson B, Morgan T (October 1976). "A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia". Pflügers Archiv. 366 (1): 11–7. doi:10.1007/BF02486556. PMID   185584. S2CID   29761514.
  6. Davis, Justin; Desmond, Michael; Berk, Michael (2018-09-24). "Lithium and nephrotoxicity: Unravelling the complex pathophysiological threads of the lightest metal". Nephrology. 23 (10). Wiley: 897–903. doi: 10.1111/nep.13263 . hdl: 11343/283773 . ISSN   1320-5358. PMID   29607573. S2CID   4552345.
  7. Christensen S, Kusano E, Yusufi AN, Murayama N, Dousa TP (June 1985). "Pathogenesis of nephrogenic diabetes insipidus due to chronic administration of lithium in rats". Journal of Clinical Investigation. 75 (6): 1869–79. doi:10.1172/JCI111901. PMC   425543 . PMID   2989335.
  8. Online Mendelian Inheritance in Man (OMIM): Diabetes Insipidus, Nephrogenic, X-linked - 304800
  9. Online Mendelian Inheritance in Man (OMIM): Diabetes Insipidus, Nephrogenic, Autosomal - 125800
  10. Kirchlechner V, Koller DY, Seidl R, Waldhauser F (June 1999). "Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride". Archives of Disease in Childhood. 80 (6): 548–52. doi:10.1136/adc.80.6.548. PMC   1717946 . PMID   10332005.
  11. Brater, Craig; H Ellison, David (November 30, 2022). "Mechanism of action of diuretics" . UpToDate . Retrieved August 19, 2024.