Treatment Of Nephrogenic Diabetes Insipidus
INTRODUCTION Nephrogenic diabetes insipidus (nephrogenic DI) results from partial or complete resistance of the kidney to the effects of antidiuretic hormone (ADH). As a result, patients with this disorder are not likely to have a good response to hormone administration (as desmopressin [dDAVP]) or to drugs that increase either the renal response to ADH or ADH secretion. Nephrogenic DI can be hereditary or acquired. In adults, a concentrating defect severe enough to produce polyuria due to nephrogenic DI is most often due to chronic lithium use or hypercalcemia and less frequently to other conditions that impair tubular function, such as Sjögren's syndrome [1]. Release of ureteral obstruction is often associated with a diuresis, but this is short lived and does not require specific therapy other than maintenance fluids. (See "Clinical manifestations and causes of nephrogenic diabetes insipidus" and "Clinical manifestations and diagnosis of urinary tract obstruction and hydronephrosis", section on 'Prognosis and recovery of renal function'.) Hereditary nephrogenic DI, which is largely an X-linked disease, may also be seen by internists since early recognition and treatment in infancy has led to survival to adulthood [2,3]. In addition, affected women may be carriers with few or no symptoms until pregnancy or other stress. In infants with hereditary nephrogenic DI, treatment is aimed at minimizing the polyuria and avoiding hypernatremia and volume depletion. In adults, therapy is usually aimed at correcting the underlying disorder or discontinuing an offending drug. In hypercalcemic patients, for example, normalization of the plasma calcium concentration usually leads to amelioration of polyuria. By contrast, lithium-induced nephrogenic DI may be irreversible if the pati Continue reading >>
Nephrogenic Diabetes Insipidus
Ongoing controversies regarding etiology, diagnosis, treatment Are you sure your patient has Nephrogenic diabetes insipidus? What are the typical findings for this disease? Diabetes insipidus (DI) is characterized by an inability to form a concentrated urine. This, in turn, causes the two most common symptoms, polyuria and polydipsia. The ability of the kidney to form a concentrated urine is dependent on adequate production and secretion of vasopressin (ADH) by the hypothalamic/pituitary axis and an intact collecting tubule vasopressin (V2) receptor/aquaporin 2 (AQP2) water channel signaling mechanism. DI occurs in two main forms, central and nephrogenic. In central (neurohypophyseal) DI there is impaired production or secretion of ADH. In nephrogenic DI (NDI), ADH is produced but the kidney is unable to respond. NDI occurs in two forms: congenital or acquired (secondary). The presence of NDI is suggested by the production of large volumes of dilute urine and hypernatremia and unresponsiveness to the administration of exogenous ADH. Failure to thrive, fever, recurrent episodes of dehydration, vomiting Congenital NDI - Congenital NDI is a genetic condition that typically presents in the first year of life with failure to thrive, fever, vomiting and recurrent episodes of dehydration. The most common form is X-linked, in which males are predominantly affected. In rare cases, heterozygote (carrier) females can display phenotypes similar to the affected males. Rare Autosomal Recessive and Autosomal Dominant forms have been reported. Acquired (Secondary) NDI - Acquired NDI is a condition that results from tubular dysfunction due to a variety of factors, including acute or chronic kidney disease, obstructive uropathy, medications, electrolyte imbalances and systemic diseases. Continue reading >>
Diabetes Insipidus Medication: Vasopressin-related Hormones, Antidiabetics, Sulfonylureas, Anticonvulsants, Diuretics, Thiazide, Nonsteroidal Anti-inflammatory Agents (nsaids), Diuretics, Potassium-sparing
Author: Romesh Khardori, MD, PhD, FACP; Chief Editor: George T Griffing, MD more... Treatment for diabetes insipidus (DI) varies with the form of the disorder. In central DI and most cases of gestational DI, the primary problem is a deficiency of antidiuretic hormone (ADH)also known as arginine vasopressin (AVP)and therefore, physiologic replacement with desmopressin is usually effective. A nonhormonal drug can be used if response is incomplete or desmopressin is too expensive. Desmopressin has no role in the treatment of nephrogenic DI or primary polydipsia. Nonhormonal drugs usually are more effective in treating nephrogenic DI. In patients with central DI, replacement of endogenous ADH with exogenous hormones prevents complications of DI and reduces morbidity. Vasopressin has vasopressor and ADH activity. It increases water resorption at collecting ducts (ADH effect). At high doses, it also promotes smooth muscle contraction throughout the vascular bed of renal tubular epithelium (vasopressor effects). However, vasoconstriction is also increased in splanchnic, portal, coronary, cerebral, peripheral, pulmonary, and intrahepatic vessels. Chlorpropamide promotes renal response to ADH. Carbamazepine possibly ameliorates DI by promoting the release of ADH. It is not useful in nephrogenic DI and generally is not a first-line drug. Hydrochlorothiazide is a thiazide diuretic that decreases urinary volume in the absence of ADH. It may induce mild volume depletion and cause proximal salt and water retention, thereby reducing flow to the ADH-sensitive distal nephron. Its effects are additive to those of other agents. Nonsteroidal Anti-inflammatory Agents (NSAIDs) The mechanism of action of NSAIDs is not known, but these agents may act by inhibiting prostaglandin synthesis. Inh Continue reading >>
Pharmacologic Treatment Of Congenital Nephrogenic Diabetes Insipidus
The purpose of this research study is to determine if two investigational medications will be more effective in decreasing urine output than the currently available and routinely used medications in patients with congenital nephrogenic diabetes insipidus (NDI). Condition or disease Intervention/treatment Nephrogenic Diabetes Insipidus Drug: sildenafil Drug: calcitonin Drug: hydrochlorothiazide/amiloride Drug: indomethacin Drug: Placebo for sildenafil Drug: placebo for calcitonin Show Detailed Description Study Type : Interventional (Clinical Trial) Actual Enrollment : 4 participants Allocation: Randomized Intervention Model: Crossover Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment Official Title: Pharmacologic Treatment of Congenital Nephrogenic Diabetes Insipidus Study Start Date : May 2007 Primary Completion Date : October 2012 Study Completion Date : October 2012 Resource links provided by the National Library of Medicine U.S. FDA Resources Arm Intervention/treatment Experimental: 1 4-day treatment with hydrochlorothiazide/amiloride, indomethacin, calcitonin, sildenafil Drug: sildenafil 25 mg quaque die (QD) or 50 mg QD x 4 days based on subject weight Other Name: Viagra Drug: calcitonin one nasal spray daily for 4 days Other Name: Miacalcic Drug: hydrochlorothiazide/amiloride 25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending on subject weight Other Name: Moduret, Moduretic Drug: indomethacin 50 mg QD or 50 mg BID x 8 days depending on subject weight Other Name: Indocin Placebo Comparator: 2 4-day treatment with hydrochlorothiazide/amiloride, indomethacin, placebo for calcitonin, placebo for sildenafil Drug: hydrochlorothiazide/amiloride 25 mg/2.5 mg BID or 50 mg/5 mg BID x 8 days depending o Continue reading >>
Diabetes Insipidus
Diabetes insipidus (DI) is a condition characterized by large amounts of dilute urine and increased thirst.[1] The amount of urine produced can be nearly 20 liters per day.[1] Reduction of fluid has little effect on the concentration of the urine.[1] Complications may include dehydration or seizures.[1] There are four types of DI, each with a different set of causes.[1] Central DI (CDI) is due to a lack of the hormone vasopressin (antidiuretic hormone).[1] This can be due to damage to the hypothalamus or pituitary gland or genetics.[1] Nephrogenic diabetes insipidus (NDI) occurs when the kidneys do not respond properly to vasopressin.[1] Dipsogenic DI is due to abnormal thirst mechanisms in the hypothalamus while gestational DI occurs only during pregnancy.[1] Diagnosis is often based on urine tests, blood tests, and the fluid deprivation test.[1] Diabetes mellitus is a separate condition with an unrelated mechanism, though both can result in the production of large amounts of urine.[1] Treatment involves drinking sufficient fluids to prevent dehydration.[1] Other treatments depend on the type.[1] In central and gestational disease treated is with desmopressin.[1] Nephrogenic disease may be treated by addressing the underlying cause or the use of a thiazide, aspirin, or ibuprofen.[1] The number of new cases of diabetes insipidus each year is 3 in 100,000.[4] Central DI usually starts between the ages of 10 and 20 and occurs in males and females equally.[2] Nephrogenic DI can begin at any age.[3] The term "diabetes" is derived from the Greek word meaning siphon.[5] Signs and symptoms[edit] Excessive urination and extreme thirst and increased fluid intake (especially for cold water and sometimes ice or ice water) are typical for DI.[6] The symptoms of excessive urination Continue reading >>
Effect Of Hydrochlorothiazide And Indomethacin Treatment On Renal Function In Nephrogenic Diabetes Insipidus.
Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus. Department of Pediatrics, Huddinge University Hospital, Karolinska Institute, Sweden. The purpose of this study was to investigate the effects of treatment with hydrochlorothiazide and hydrochlorothiazide and indomethacin combined on renal function in four boys, two with nephrogenic diabetes insipidus and two with partial nephrogenic diabetes insipidus using the clearances of inulin and para-aminohippuric acid under water diuresis and lithium clearance. Hydrochlorothiazide reduced urine flow and lithium clearance. These effects were further potentiated by addition of indomethacin. No consistent effects on renal plasma flow or glomerular filtration rate were found. It is concluded that treatment with hydrochlorothiazide alone and hydrochlorothiazide and indomethacin combined reduces urine flow in nephrogenic diabetes insipidus by increasing proximal tubular reabsorption of sodium. Continue reading >>
Payperview: Hydrochlorothiazide-amiloride In The Treatment Of Congenital Nephrogenic Diabetes Insipidus - Karger Publishers
I have read the Karger Terms and Conditions and agree. The effects of treatment with hydrochlorothiazide combined with amiloride were compared to hydrochlorothiazide treatment alone in 2 brothers with congenital nephrogenic diabetes insipidus. Whereas both modalities of treatment resulted in reduction in voiding frequency and urine volume, decrease in daily fluid intake and increase in urine osmolality, the two-drug combination was found to be superior to hydrochlorothiazide alone by preventing urinary potassium losses, hypokalemia, and alkalosis. It was also found that amiloride had a certain additive effect to the thiazide in terms of increasing initial urinary sodium excretion, reducing urine volume and free water clearance, and lowering serum sodium concentration and osmolality. Similar comparison of the hydrochlorothiazide-amiloride regimen to treatment with the hydrochlorothiazide-tolmetin combination in 1 of the patients revealed that the effectiveness of both diuretic modalities was close with slight advantage of the former. Treatment of the 2 patients for 10 months with hydrochlorothiazide and amiloride showed no adverse effects and consistent reduction in fluid intake and urine volume. It is concluded that the hydrochlorothiazide-amiloride regimen is superior to hydrochlorothiazide alone and can be a satisfactory alternative to the hydrochlorothiazide-prostaglandin synthetase inhibitor combination in the treatment of congenital nephrogenic diabetes insipidus. Continue reading >>
Indomethacin In The Treatment Of Lithium-induced Nephrogenic Diabetes Insipidus
Indomethacin in the Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus Indomethacin in the Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder. In a letter to the editor of the Archives of Internal Medicine, Vierhapper notes that Allon may have oversimplified the case for the drug indomethacin in regards to treatment for nephrogenic diabetes insipidus ( NDI ). Allon had previously written that indomethacin , which is used to help reduce the excessive urine volume in congenital NDI patients, might also be effective in reducing the urine volume of patients whose NDI was induced by long-term use of lithium . The implication seemed to be that indomethacin reduces the urine volume solely by inhibiting cyclo-oxygenase activity. But other tests show that a mechanism other than cyclo-oxygenase inhibition is involved in the effect of indomethacin . Thus, to relate the antidiuretic ( urine reducing) action of indomethacin only to its inhibiting effect on cyclo-oxygenase is an oversimplification. Allon replied that in addition to inhibiting cyclo-oxygenase activity, indomethacin also inhibits other enzyme systems, such as phosphodiesterase . Thus, the antidiuretic effect of indomethacin may be related to these other effects, rather than to just prostaglandin inhibition . However, even though it is not possible to definitely conclude Continue reading >>
Indomethacin In The Treatment Of Lithium-induced Nephrogenic Diabetes Insipidus.
Indomethacin in the treatment of lithium-induced nephrogenic diabetes insipidus. Department of Medicine, University of Oklahoma School of Medicine, Oklahoma City 73104. Nephrogenic diabetes insipidus (NDI) is a frequent complication in patients receiving long-term lithium therapy. Both thiazide diuretics and amiloride may reduce the polyuria, but the use of each is associated with problems. We report the results of a clinical trial using the nonsteroidal anti-inflammatory drug indomethacin to treat a patient with well-documented lithium-induced NDI that persisted following cessation of lithium treatment. The administration of a single dose of indomethacin resulted in a dramatic decrease in urine volume and increase in urine osmolality that persisted for several hours, and was independent of renal hemodynamic changes. Subsequently, the patient experienced a sustained, favorable effect on her polyuria during long-term (3 months) indomethacin therapy without a deleterious effect on her renal function. Indomethacin may be a useful therapeutic tool for the amelioration of lithium-induced NDI. Continue reading >>
Indomethacin In The Treatment Of Lithium-induced Nephrogenic Diabetes Insipidus
To the Editor. — In a recent communication, Allen et al1 report that indomethacin, a compound used for some time2 to reduce diuresis in nephrogenic diabetes insipidus, may also be effective in patients in whom this condition has been induced by lithium therapy. Since in the interpretation of their results, indomethacin is used virtually synonymously with "NSAID" the authors should be reminded that both in healthy subjects and in a patient with nephrogenic diabetes insipidus, the comparison of the potential antidiuretic effect of indomethacin vs that of acetylsalicylic acid, another inhibitor of cyclo-oxygenase activity, has indicated that a mechanism other than cyclo-oxygenase inhibition is involved in the effect of indomethacin.3,4 To relate the antidiuretic action of indomethacin in nephrogenic diabetes insipidus only to its effect on cyclo-oxygenase is therefore an oversimplification. Continue reading >>
Clinical Presentation And Follow-up Of 30 Patients With Congenital Nephrogenic Diabetes Insipidus
Clinical Presentation and Follow-Up of 30 Patients with Congenital Nephrogenic Diabetes Insipidus * Department of Pediatrics University Hospital Nijmegen, The Netherlands. Department of Human Genetics, University Hospital Nijmegen, The Netherlands. Correspondence to Dr. Angenita F. van Lieburg, Department of Pediatrics, University Hospital Nijmegen, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. Phone: 31 24 3616872; Fax: 31 24 3616428; E-mail: F.verhoeven{at}mailbox.kun.nl Received for publication December 15, 1998. Abstract. Congenital nephrogenic diabetes insipidus is characterized by insensitivity of the distal nephron to arginine vasopressin. Clinical knowledge of this disease is based largely on case reports. For this study, data were collected on clinical presentation and during long-term follow-up of 30 male patients with congenital nephrogenic diabetes insipidus. The majority of patients (87%) were diagnosed within the first 2.5 yr of life. Main symptoms at clinical presentation were vomiting and anorexia, failure to thrive, fever, and constipation. Three older patients were diagnosed as a result of events not directly related to the disease. Except for a possibly milder phenotype in patients with a G185C mutation, no clear relationship between clinical and genetic data could be found. Most patients were on hydrochlorothiazide-amiloride treatment without significant side effects. Two patients suffered from severe hydronephrosis with a small rupture of the urinary tract after a minor trauma, and two patients experienced episodes of acute urine retention. Height SD scores for age remained below the 50th percentile in the majority of patients, whereas weight for height SD scores showed a catch-up after several years of underweight. Congenital nephrogenic diab Continue reading >>
New Insights Into The Paradoxical Effect Of Thiazides In Diabetes Insipidus Therapy
New insights into the paradoxical effect of thiazides in diabetes insipidus therapy Hospital das Clnicas da Fac. de Medicina da Univ. de So Paulo, So Paulo, Brazil Search for other works by this author on: Nephrology Dialysis Transplantation, Volume 15, Issue 12, 1 December 2000, Pages 19031905, Antonio J. Magaldi; New insights into the paradoxical effect of thiazides in diabetes insipidus therapy, Nephrology Dialysis Transplantation, Volume 15, Issue 12, 1 December 2000, Pages 19031905, One of the great advances in the therapy of renal disease occurred in the 1930s and was the synthesis of orally administered diuretic compounds. In 1937 suphanilamides had been introduced as antimicrobiological agents. In patients treated with suphanilamides, metabolic acidosis with alkaline urine was observed. Pursuance of this phenomenon led to the accidental discovery of the diuretic effect of suphanilamides. In 1940 it was found that some suphanilamides inhibited carboanhydrase. An intensive search for suphanilamides without carboanhydrase inhibition led to the synthesis of benzothiazide by Novello and Sprague [ 1 ]. Subsequently, numerous congeners were synthesized which are widely used today. The principal site of thiazide action is the distal convoluted tubule, where they inhibit the NaCl cotransporter in the luminal membrane, thus decreasing the Cl and Na+ reabsorption. In 1990 Tran et al. [ 2 ] studied metolazone, a thiazide type diuretic and suggested that thiazides occupy the Cl binding site of the Na+Cl cotransporter. In this position, metolazone impedes the chloride entrance into the transporter molecule, thus blocking the reabsorption of the ion. The principal adverse effect produced by thiazides is potassium loss with consecutive hypokalaemia. Such potassium loss is basi Continue reading >>
A Case Of Nephrogenic Diabetes Insipidus Which Was Successfully Treated With High-dose Indomethacin
A case of nephrogenic diabetes insipidus which was successfully treated with high-dose indomethacin Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Department of Emergency and Critical Care Medicine, Fukuoka University Hospital Released on J-STAGE: May 02, 2016 [Advance Publication] Released: - Received: October 23, 2014 Revised: - Accepted: August 04, 2015 Indomethacin is a medication for nephrogenic diabetes insipidus. We herein report a case that was successfully treated with high-dose indomethacin (225 mg/day) for nephrogenic diabetes insipidus. A 35-year-old female had been receiving treatment for manic depression psychosis with lithium since 18 years of age. She was transferred to our emergency center due to an overdose of ingested phenobarbital and chlorpromazine. On the second hospital day, she developed hypernatremia and polyuria (over 450 ml/hr) which proved to be resistant to treatment with vasopressin. We diagnosed her to have nephrogenic diabetes insipidus. Because she had been taking lithium for manic depression psychosis for the previous 17 years, lithium was thus suspected to be the cause of diabetes insipidus. After diagnosing the patient to have nephrogenic diabetes insipidus, we discontinued lithium administration and switched the treatment to an indomethacin suppository (150 mg/day). However, her symptoms persisted. We consid Continue reading >>
Indomethacin In The Treatment Of Lithium-induced Nephrogenic Diabetes Insipidus-reply
Indomethacin in the Treatment of Lithium-Induced Nephrogenic Diabetes Insipidus-Reply In Reply.Dr Vierhapper correctly points out that, in addition to the inhibition of cyclo-oxygenase activity, indomethacin also inhibits other enzyme systems, such as phosphodiesterase. Thus, the antidiuretic effect of indomethacin may be related to these other effects, rather than just to prostaglandin synthesis inhibition. However, an antidiuretic effect in patients with congenital nephrogenic diabetes insipidus has been observed not only with indomethacin, 1-5 but also with two unrelated nonsteroidal anti-inflammatory drugs, acetylsalicylic acid5 and tolmetin.6 Similarly, in healthy waterloaded subjects, an antidiuretic effect has been reported not only with indomethacin, but also with carprofen7 and oxaprozin.8 Whereas Vierhapper et al9 found no significant effect of acetylsalicylic acid on diuresis in normal subjects, Berg10 demonstrated a substantial reduction in urine flow with this drug in patients with chronic renal insufficiency. It is not possible to definitively conclude that the antidiuretic effect of indomethacin is Continue reading >>
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Renal Prostaglandin E2 In Nephrogenic Diabetes Insipidus: Effects Of Inhibition Of Prostaglandin Synthes Is By Indomethacin
RENAL PROSTAGLANDIN E2 IN NEPHROGENIC DIABETES INSIPIDUS: EFFECTS OF INHIBITION OF PROSTAGLANDIN SYNTHES IS BY INDOMETHACIN Pediatric Research volume 14, page 1008 (1980) Urinary prostaglandin E2 (PGE2) and cyclic AMP(AMPc) were determined in two children with nephrogenic diabetes insipidus(NDI) under basal conditions, after intranasal DDAVP and after 3-day treatment with indomethacin(3mg/Kg b.w./day).In one case PGE2 was very high, rose after DDAVP and fell to approximately normal values after indomethacin(-73%). In this case basal AMPc was high, showed minimal modifications after DDAVP(+12%), but decreased sharply after indomethacin(-50%). In the second case PGE2 were slightly above normal values, rose after DDAVP(+28%) and were undetectable after indomethacin. Basal AMPc was high, fell after DDAVP(-21%) and rose after indomethacin(+35%). In both cases there was a marked fall of diuresis, CH2O, EFNa and of the distal delivery(CH2O+CNa) after indomethacin, while GFR fell slightly. Distal fractional reabsorption of sodium (CH2O/CH2O+CNa) was unaffected by the drug. We suggest 1) that the adenyl-cyclase system is intact in NDI and the PGE2, as well as ADH, is responsible for the variations in urinary AMPc. A very high level of PGE2 can itself stimulate AMPc and may increase the AMPc production induced by exogenous ADH. In contrast, concentrations of PGE2 slightly above normal values probably have a minimal effect on basal AMPc, but they reduce the stimulation of AMPc mediated by exogenous vasopressin. 2) That the antidiuresis induced by indomethacin treatment in NDI is due to enhanced proximal tubular reabsorption. Broyer M.- Hpital des Enfants Malades, Paris, Franco. Continue reading >>
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