Treatment of Congenital Nephrogenic Diabetes Insipidus by Hydrochlorothiazide and Cyclooxygenase-2 Inhibitor
| Title: | Treatment of Congenital Nephrogenic Diabetes Insipidus by Hydrochlorothiazide and Cyclooxygenase-2 Inhibitor |
|---|---|
| Authors: | Pattaragarn, Anirut; Alon, M.D., Uri S. |
| Publisher: | Pediatric Nephrology |
| Date Published: | October 01, 2003 |
| Reference Number: | 620 |
A 1-month-old male infant presented with failure to thrive, polyuria, and severe hypernatremic dehydration. Based on family history, lack of response to vasopressin, and normal sonography of the urinary system, the diagnosis of congenital nephrogenic diabetes insipidus (cNDI) was established. The infant responded well to indomethacin in combination with hydrochlorothiazide (HCTZ), but quickly developed gastrointestinal bleeding. The substitution of indomethacin by amiloride and later by tolmetin was found to be ineffective. Treatment with HCTZ (3 mg/kg per day) and rofecoxib (1 mg/kg per day, both divided into three doses) combined with a low-salt formula resulted in a dramatic decrease in urinary free water losses. No side effects of the combination were noted. At age 8.5 months, the infant demonstrated catch-up growth and normal neurodevelopmental milestones. We conclude that the combination HCTZ/cyclooxygenase-2 inhibitor could be successfully used to treat infantile cNDI.
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)
This treatment reduced the patient’s urine volume, but he quickly developed gastrointestinal bleeding in reaction to indomethacin. The doctors replaced the indomethacin first with amiloride, then with tolmetin, but neither of these proved effective. They then tried rofecoxib in combination with HCTZ, and this proved effective in reducing the NDI symptoms and stimulated no unwanted side effects. The infant was discharged from the hospital and is developing normally.
Rofecoxib is a cyclooxygenase-2 (COX-2) inhibitor, i.e., it interferes with the function of COX-2, which is to help form prostaglandins. COX-2 is found in cells in the kidney glomerulus and in small blood vessels in the kidney. This suggests that it helps regulate the movement of the blood in the kidneys. When COX-2 inhibits prostaglandins in these areas, it does not interfere with the prostaglandins in the gastrointestinal area.
COX-2, then, reduces urinary sodium excretion without the gastrointestinal side effects that indomethacin caused. In combination with HCTZ, it helped decrease the infant’s urine flow by around 72% and decreased his free water clearance by 83% compared to the HCTZ/tolmetin combination.
The researchers report that HCTZ/rofecoxib is not a panacea, however, and that it could produce side effects in people with certain other conditions. They warn that patients using this drug combination should be closely watched for side effects and that, in the case of their patient, amiloride should be substituted for rofecoxib when he gets older.
OF NOTE: Dr. Alon reports that the younger brother of the patient, now 5 months, was also diagnosed with NDI, and has too responded favorably to the combination of hydrochlorothiazide and rofecoxib.