Fibrinolytic Responses to 1-Desamino-8-<i>D</i>-Arginine-Vasopressin in Patients with Congenital Nephrogenic Diabetes insipidus

Abstract

Fibrinolytic responses to infusion of 1-desamino-8-.D-arginine-vasopressin (DDAVP) were assessed in 6 males with congenital nephrogenic diabetes insipidus (NDI), 6 carriers of the NDI gene and 6 normal control subjects. Tissue-type plasminogen activator (t-PA) activity and antigen increased significantly in normal subjects, while plasminogen activator inhibitor (PAI) activity decreased. None of these changes were observed in patients with NDI. In 2 female carriers, normal fibrinolytic responses were seen, while in the other carriers responses were delayed. These findings are consistent with the concept of a general V₂-receptor defect in congenital NDI. DDAVP tests are of limited use in NDI carrier detection.

A variant of nephrogenic diabetes insipidus: V2 receptor abnormality restricted to the kidney

“…It provokes a marked transient release of von Willebrand factor antigen (vWF:ag), factor VIII coagulant activity and plasminogen activator [6] from endothelial storage sites and exerts a vasodilatory action manifested by facial flushing, a fall in diastolic blood pressure and a rise in pulse rate [5]. Recent studies have demonstrated that patients with NDI do not show these changes in haemodynamic [2], coagulation [2,10] and fibrinolytic [9] parameters after administration of DDAVP. Contrasting with these observations, the study is presented of a 4-year-old boy with severe NDI, who had normal vWF:ag, plasminogen activator and vasodilatory responses to DDAVP.…”

Inheritance of mutations in the V2 receptor gene in thirteen families with nephrogenic diabetes insipidus

“…In addition to mediating antidiuresis, an apparent V2 mediated action of AVP and its V2-specific agonist, l-desamino-8-D-arginine vasopressin (DDAVP), causes release of coagulation and fibrinolytic factors (2] and vasodilation [3]. These extra-Received for publication August 11, 1993 and in revised form January 24,1994 Accepted for publication January 24, 1994 © 1994 by the International Society of Nephrology renal responses are also absent in NDI patients [4][5][6], suggesting that the defect in this disorder might be a dysfunctional or nonfunctional vasopressin V2 receptor.…”

Normal Fibrinolytic Responses to 1 -Desamino-8-<i>D</i>-Arginine Vasopressin in Patients with Nephrogenic Diabetes insipidus Caused by Mutations in the Aquaporin 2 Gene

“…Tissue-type plasminogen activator antigen (tPA:Ag) was measured by an en zyme-linked immunoassay (Innotest, Chromogenix, Zwijndrecht, Belgium). Data were compared with those obtained from 6 NDI patients [3] in whom a V2 receptor gene mutation had been found.…”

“…In addition to its renal antidiuretic action. DDAVP elicits vasodila tion and an increase of coagulation and fibrinolysis fac tors [2,3]. The exact location of the V2 receptors which mediate these effects is unknown.…”

“…most NDI patients lack the extrarenal responses to DDAVP. indicating a generalized V2 receptor defect [3,[7][8][9]. Evidence for the hypothesis that a V2 receptor defect causes NDI was gained when mutations in the V2 receptor gene were found in patients with the X-linked recessive form of the disease [10].…”