Nephrogenic Diabetes Insipidus in Sibling Colts
|Title:||Nephrogenic Diabetes Insipidus in Sibling Colts|
|Authors:||Schott II, DVM, Harold C.; Bayly, BVSc, MS, Warwick M.; Reed, DVM, Stephen M.; Brobst, DVM, Duane F.|
|Publisher:||Journal of Veterinary Internal Medicine|
|Date Published:||March 1993 - April 1993|
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.
© Copyright NDI Foundation 2007 (JC)
Normally, AVP binds to a vasopressin-2 receptor (V2R). This initiates a cascade of events leading to the increase of an important metabolic regulator called cAMP in the principal cells of the kidney collecting ducts. This increase leads, through a series of steps as yet unknown, to the insertion of specific water transporting proteins called aquaporin-2 (AQP2) into specific kidney cell membranes. Once inserted in the membranes, the AQP2s make them much more permeable to water. This increase in water flow through the cell membranes allow the kidneys to reabsorb water and concentrate urine.
People with hereditary NDI either have a defect in the V2R gene which prevents the V2R from binding with AVP, or, much less commonly, they have a defect in the AQP2 gene which prevents the AQP2s from inserting themselves in the collecting duct cell membranes. In both instances, the kidney is rendered unable to concentrate urine or reabsorb water.
The V2R gene is located on the X chromosome, so cases of NDI resulting from mutations of the V2R are called X-linked NDI. This means that females carry the mutated gene (which is recessive), but it is mostly males who are affected by it. Another cause of diabetes insipidus is the failure of the pituitary gland to produce enough AVP. This form of DI is called neurogenic DI and although its symptoms are the same as NDI, it is treated differently. Injections of synthetic AVP compensate for the lack of normal AVP. Whereas in NDI, there is enough AVP naturally, but the kidney cannot respond to it. So the treatment involves maintaining a low sodium diet and taking thiazide diuretics.
There are about a million little tubes called tubules in each kidney, and each is attached to a filtering unit called a glomerulus. Together they are called a nephron and they are the functional units of the kidney. Thiazide diuretics inhibit sodium reabsorption in the part of the tubule further away from glomerulus, and increases solute delivery to the kidney collecting duct. (Solutes are the solid particles in a solution, e.g. the salt in saltwater.) This regime helps reduce polyuria somewhat. Recently, treatment with prostaglandin inhibitors or amiloride has been reported to decrease polyuria in NDI patients.
Schott II, et al., report on their diagnosis of NDI in two full sibling thoroughbred colts (young male horses). Additionally, a third half-sibling colt (same mother, different father) appeared to have NDI, but was destroyed before a clinical evaluation could be carried out.
The two colts each had extreme polyuria and polydipsia. They could not concentrate urine after a water fast or upon administration of a synthetic analog of AVP or a concentrated saline solution, all classic responses of NDI. (Both colts developed severe dehydration after the overnight water fast, which emphasized the importance of close patient monitoring during the process. There is no advantage in maintaining water deprivation beyond the recommended 5% loss of body weight.)
The mother of these colts had ten offspring: five males and five females. All the females were normal. Occurrence of NDI in two males (and possibly a third) suggests that NDI may be inherited as an X-linked disorder in horses, just as it is in people.