The clinical use of thiazides in nephrogenic diabetes insipidus. Drugs are the most important causes of NDI . This condition is characterized by unresponsiveness of the kidney to the action of vasopressin.
Why are thiazide diuretics used in nephrogenic diabetes insipidus?
Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear.
How do thiazides work in nephrogenic diabetes insipidus?
In fact, the most widely accepted hypothesis suggests that the antidiuretic action of thiazides is secondary to increased renal sodium excretion (1,2,6⇓⇓). The renal sodium loss causes extracellular volume contraction leading to lowered GFR and increased proximal tubular sodium and water reabsorption.
What drugs can cause nephrogenic diabetes insipidus?
Causes of nephrogenic diabetes insipidus in adults include: Lithium, a drug most commonly taken for bipolar disorder; up to 20% of people taking lithium will develop nephrogenic diabetes insipidus. Other medicines, including demeclocycline (Declomycin), ofloxacin (Floxin), orlistat (alli, Xenical), and others.
What is the most common cause of nephrogenic diabetes insipidus?
Lithium is the most common cause of acquired nephrogenic diabetes insipidus. It’s a medication often used to treat bipolar disorder. Long-term lithium use can damage the cells of the kidneys so they no longer respond to AVP.
Why thiazides are contraindicated in diabetes?
Prolonged thiazide diuretic therapy can lead to glucose intolerance and may occasionally precipitate diabetes mellitus. Short-term metabolic studies, epidemiologic studies, and a variety of clinical trials suggest a connection between ongoing thiazide diuretic use and the development of type 2 diabetes.
Why do thiazides cause hyperglycemia?
The effect of the thiazide-induced short-term changes in serum lipids is unclear. Present experience suggests that thiazide-induced impairment of glucose tolerance is due to both reduced glucose-stimulated insulin release and increased peripheral resistance to the action of insulin.
How do thiazides work?
Thiazide diuretics work by blocking sodium and chloride (Na/Cl) channels in the distal convoluted tubule of the nephron and inhibit the reabsorption of sodium and water. This also causes a loss of potassium and calcium ions.
How do thiazides increase lithium?
Thiazide diuretics have a significant potential to increase serum lithium concentrations. These diuretics induce a natriuresis that leads to a compensatory increase in the reabsorption of sodium (and lithium) in the proximal tubule (5).
How can thiazide diuretics effectively reduce hypertension?
By decreasing sodium reabsorption, thiazide use acutely results in an increase in fluid loss to urine, which leads to decreased extracellular fluid (ECF) and plasma volume. This volume loss results in diminished venous return, increased renin release, reduced cardiac output and decreased blood pressure .
How common is nephrogenic diabetes insipidus?
The prevalence of nephrogenic diabetes insipidus is unknown, although the condition is thought to be rare. The acquired form occurs more frequently than the hereditary form.
How do NSAIDs treat nephrogenic diabetes insipidus?
Blockade of prostaglandin E(2) synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies.
Why does lithium cause nephrogenic diabetes insipidus?
Chronic lithium therapy can lead to accumulation in distal tubular cells causing impaired urinary concentrating ability. This can lead to partial or full nephrogenic diabetes insipidus. It is estimated to be present in up to 40% of patients on chronic lithium therapy .
Is diabetes insipidus autosomal dominant or recessive?
Familial neurohypophyseal diabetes insipidus is almost always inherited in an autosomal dominant pattern , which means one copy of the altered AVP gene in each cell is sufficient to cause the disorder. In a few affected families, the condition has had an autosomal recessive pattern of inheritance.
Who does nephrogenic diabetes insipidus affect?
The autosomal dominant, autosomal recessive and acquired forms of NDI affect males and females in equal numbers. The symptoms of NDI may begin at any age, usually rapidly and without warning. The incidence of NDI is not known; the X-linked form is estimated to affect 4 males out of every 1,000,000.
How is central insipidus different from nephrogenic diabetes?
Generally, an increase in urine osmolality of greater than 50% reliably indicates central diabetes insipidus, while an increase of less than 10% indicates nephrogenic diabetes insipidus; responses between 10% and 50% are indeterminate.