Successful Treatment with Hydrochlorothiazide and Amiloride in an Infant with Congenital Nephrogenic Diabetes Insipidus

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Title: Successful Treatment with Hydrochlorothiazide and Amiloride in an Infant with Congenital Nephrogenic Diabetes Insipidus
Authors: Uyeki, Timothy M.; Barry, Floyd L.; Rosenthal, Stephen M.; Mathias, Robert S.
Publisher: Pediatric Nephrology
Date Published: October 01, 1993
Reference Number: 121
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We report a 9-month-old male Latino infant with congenital nephrogenic diabetes insipidus (NDI) who presented with hypernatremic dehydration aggravated by severe gastroenteritis. Initially, the infant was managed with intravenous fluids followed by standard 20 cal/ounce formula and pharmacological therapy, resulting in normalization of his serum sodium level. While hydrochlorothiazide therapy alone or in combination with prostaglandin inhibitors or amiloride has been successful in children and adolescents, this is the first report of the successful use of hydrochlorothiazide and amiloride in an infant with congenital NDI.

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)

Congenital nephrogenic diabetes insipidus (NDI) is a disorder where the kidney is unable to respond to the antidiuretic hormone, arginine vasopressin (AVP). Therefore it is not able to reabsorb body water and concentrate urine. The major symptoms of NDI are polyuria (the chronic passage of large volumes of urine) and polydipsia (chronic, excessive thirst). An infant born with NDI may start displaying clinical symptoms the first week of life which, in addition to those mentioned above, include fever, irritability, failure to thrive, vomiting, constipation, high blood sodium and bouts of dehydration that, if untreated, could cause physical and mental retardation, and even death.

The most common type of congenital NDI is X-linked NDI, which is carried by females and expressed by males. The molecular basis for X-linked NDI is mutations of the vasopressin-2 receptor (V2R) gene, which render the vasopressin-2 receptors they produce incapable of carrying out their function of binding with AVP. Thus, the molecular sequence which results in water reabsorption and urine concentration cannot take place.

The nephrons are the major working unit of the kidney. There are about a million of them in each kidney and each consists of a filtration unit called a glomerulus and a little tube called a tubule. The tubule has several sections. The section nearest the glomerulus is called the proximal tubule and the section furthest from the glomerulus is called the distal tubule. The section in-between these two sections is called the loop of Henle. The distal tubule turns into the kidney collecting duct where the V2R reside in its principal cells.

Uyeki, et al., report on a 9-month-old Latino male diagnosed with X-linked NDI. Once diagnosed, the treating physicians made sure the infant had an adequate water intake to counter the fluid loss brought on by his polyuria. In addition, he was placed on a low sodium diet and the drugs hydrochlorothiazide and amiloride to help reduce his polyuria. Hydrochlorothiazide is thought to help decrease urine volume by inhibiting sodium dependent chloride transport in the distal tubules. This leads to increased proximal tubule fluid absorption. Amiloride promotes the excretion of sodium by inhibiting sodium uptake in the distal tubule and the collecting duct.

Chronic use of hydrochlorothiazide often leads to increased urinary potassium excretion, low blood potassium and alkalosis (the accumulation of base or loss of acid in the body without a comparable loss of base in the body fluids). Thus, the infant was placed on potassium supplementation. Amiloride is a potassium-sparing diuretic, and this property is helpful in not further depleting the blood potassium of a person who takes it.

The infant was discharged from the hospital after 18 days and continued on his dietary and pharmacological regime. Though the drugs do not cure NDI, they did reduce the infants symptoms and helped stabilize his blood chemistry, allowing him to develop normally. This was the first known successful use of hydrochlorothiazide and amiloride in an infant with NDI. Further study is needed to determine whether long-term therapy with these drugs in infants with NDI is beneficial.