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      Conivaptan: a step forward in the treatment of hyponatremia?

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          Abstract

          Hyponatremia is one of the most common electrolyte abnormalities linked to adverse outcomes and increased mortality in hospitalized patients. While the differential diagnosis for hyponatremia is diverse, most cases stem from arginine vasopressin (AVP) dysregulation, where hypoosmolality fails to suppress AVP synthesis and release. The physiological effects of AVP are currently known to depend on its interaction with any of 3 receptor subtypes V1A, V2, and V1B. Activation of V2 by AVP is the key in renal water regulation and maintenance of total body volume and plasma tonicity. Despite the long-recognized problem with excess AVP in euvolemic and hypervolemic hyponatremia, traditional therapeutic options have relied on nonspecific and potentially problematic strategies. More recently, a new class of drugs, introduced as “aquaretics,” has gained great attention among clinicians because of its ability to correct hyponatremia via direct competitive inhibition of AVP at V2 receptors to induce renal electrolyte-free water excretion. In this paper, we aim to review available clinical data on the only FDA-approved aquaretic, dual V1A/V2 receptor antagonist conivaptan, discuss its clinical indications, efficacy, safety profile, and comment on its clinical limitations.

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          Most cited references 58

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          Inhibition of renal cystic disease development and progression by a vasopressin V2 receptor antagonist.

          The polycystic kidney diseases (PKDs) are a group of genetic disorders causing significant renal failure and death in children and adults. There are no effective treatments. Two childhood forms, autosomal recessive PKD (ARPKD) and nephronophthisis (NPH), are characterized by collecting-duct cysts. We used animal models orthologous to the human disorders to test whether a vasopressin V2 receptor (VPV2R) antagonist, OPC31260, would be effective against early or established disease. Adenosine-3',5'-cyclic monophosphate (cAMP) has a major role in cystogenesis, and the VPV2R is the major cAMP agonist in the collecting duct. OPC31260 administration lowered renal cAMP, inhibited disease development and either halted progression or caused regression of established disease. These results indicate that OPC31260 may be an effective treatment for these disorders and that clinical trials should be considered.
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            Effective treatment of an orthologous model of autosomal dominant polycystic kidney disease.

            Autosomal dominant polycystic kidney disease (ADPKD) is a leading cause of end-stage renal disease. The vasopressin V2 receptor (VPV2R) antagonist OPC31260 has been effective in two animal models of PKD with pathologies that are probably related. Here we show, in a mouse model of ADPKD (Pkd2(-/tm1Som)), a similar cellular phenotype and response to OPC31260 treatment, with reduction of renal cyclic AMP (cAMP) levels, prevention of renal enlargement, marked inhibition of cystogenesis and protection of renal function.
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              The syndrome of inappropriate secretion of antidiuretic hormone.

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                Author and article information

                Journal
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                April 2008
                April 2008
                : 4
                : 2
                : 315-326
                Affiliations
                [1 ]Olive View-UCLA Medical Center, Department of Medicine, Nephrology Division Sylmar, CA, USA
                [2 ]Pennsylvania State Worthington Scranton Dunmore, PA, USA
                [3 ]David Geffen School of Medicine at UCLA Medical Center Los Angeles, CA, USA
                [4 ]Mather VA Medical Center Mather, CA, USA
                Author notes
                Correspondence: Phuong-Chi T Pham Olive View-UCLA Medical Center, Department of Medicine, Nephrology Division, 14445 Olive View Drive, 2B-182, Sylmar, CA 91342, USA Tel +1 818 364 3205 Fax +1 818 364 4573 Email pctp@ 123456ucla.edu
                Article
                2504060
                18728836
                © 2008 Dove Medical Press Limited. All rights reserved
                Categories
                Review

                Medicine

                hypervolemia, avp receptor antagonist, hyponatremia, conivaptan, euvolemia, avp

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