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. 1999 Jun;80(6):548–552. doi: 10.1136/adc.80.6.548

Treatment of nephrogenic diabetes insipidus with hydrochlorothiazide and amiloride

V Kirchlechner 1, D Koller 1, R Seidl 1, F Waldhauser 1
PMCID: PMC1717946  PMID: 10332005

Abstract

Nephrogenic diabetes insipidus (NDI) is characterised by the inability of the kidney to concentrate urine in response to arginine vasopressin. The consequences are severe polyuria and polydipsia, often associated with hypertonic dehydration. Intracerebral calcification, seizures, psychosomatic retardation, hydronephrosis, and hydroureters are its sequelae. In this study, four children with NDI were treated with 3 mg/kg/day hydrochlorothiazide and 0.3 mg/kg/day amiloride orally three times a day for up to five years. While undergoing treatment, none of the patients had signs of dehydration or electrolyte imbalance, all showed normal body growth, and there was no evidence of cerebral calcification or seizures. All but one had normal psychomotor development and normal sonography of the urinary tract. However, normal fluid balance was not attainable (fluid intake, 3.8-7.7 l/m2/day; urine output, 2.2-7.4 l/m2/day). The treatment was well tolerated and no side effects could be detected. Prolonged treatment with hydrochlorothiazide/amiloride appears to be more effective and better tolerated than just hydrochlorothiazide. Its efficacy appears to be similar to that of hydrochlorothiazide/indomethacin but without their severe side effects.



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Selected References

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  1. Alon U., Chan J. C. Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol. 1985;5(1):9–13. doi: 10.1159/000166896. [DOI] [PubMed] [Google Scholar]
  2. Bichet D. G., Arthus M. F., Lonergan M., Hendy G. N., Paradis A. J., Fujiwara T. M., Morgan K., Gregory M. C., Rosenthal W., Didwania A. X-linked nephrogenic diabetes insipidus mutations in North America and the Hopewell hypothesis. J Clin Invest. 1993 Sep;92(3):1262–1268. doi: 10.1172/JCI116698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bichet D. G., Hendy G. N., Lonergan M., Arthus M. F., Ligier S., Pausova Z., Kluge R., Zingg H., Saenger P., Oppenheimer E. X-linked nephrogenic diabetes insipidus: from the ship Hopewell to RFLP studies. Am J Hum Genet. 1992 Nov;51(5):1089–1102. [PMC free article] [PubMed] [Google Scholar]
  4. Bichet D. G. Nephrogenic diabetes insipidus. Semin Nephrol. 1994 Jul;14(4):349–356. [PubMed] [Google Scholar]
  5. Bichet D. G., Oksche A., Rosenthal W. Congenital nephrogenic diabetes insipidus. J Am Soc Nephrol. 1997 Dec;8(12):1951–1958. doi: 10.1681/ASN.V8121951. [DOI] [PubMed] [Google Scholar]
  6. Bichet D. G. Vasopressin receptors in health and disease. Kidney Int. 1996 Jun;49(6):1706–1711. doi: 10.1038/ki.1996.252. [DOI] [PubMed] [Google Scholar]
  7. CRAWFORD J. D., KENNEDY G. C. Chlorothiazid in diabetes insipidus. Nature. 1959 Mar 28;183(4665):891–892. doi: 10.1038/183891a0. [DOI] [PubMed] [Google Scholar]
  8. Deen P. M., Verdijk M. A., Knoers N. V., Wieringa B., Monnens L. A., van Os C. H., van Oost B. A. Requirement of human renal water channel aquaporin-2 for vasopressin-dependent concentration of urine. Science. 1994 Apr 1;264(5155):92–95. doi: 10.1126/science.8140421. [DOI] [PubMed] [Google Scholar]
  9. Hoekstra J. A., van Lieburg A. F., Monnens L. A., Hulstijn-Dirkmaat G. M., Knoers V. V. Cognitive and psychosocial functioning of patients with congenital nephrogenic diabetes insipidus. Am J Med Genet. 1996 Jan 2;61(1):81–88. doi: 10.1002/(SICI)1096-8628(19960102)61:1<81::AID-AJMG17>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  10. Jakobsson B., Berg U. Effect of hydrochlorothiazide and indomethacin treatment on renal function in nephrogenic diabetes insipidus. Acta Paediatr. 1994 May;83(5):522–525. doi: 10.1111/j.1651-2227.1994.tb13072.x. [DOI] [PubMed] [Google Scholar]
  11. Kluge M., Riedl S., Erhart-Hofmann B., Hartmann J., Waldhauser F. Improved extraction procedure and RIA for determination of arginine8-vasopressin in plasma: role of premeasurement sample treatment and reference values in children. Clin Chem. 1999 Jan;45(1):98–103. [PubMed] [Google Scholar]
  12. Knoers N., Monnens L. A. Amiloride-hydrochlorothiazide versus indomethacin-hydrochlorothiazide in the treatment of nephrogenic diabetes insipidus. J Pediatr. 1990 Sep;117(3):499–502. doi: 10.1016/s0022-3476(05)81106-0. [DOI] [PubMed] [Google Scholar]
  13. Knoers N., Monnens L. A. Nephrogenic diabetes insipidus: clinical symptoms, pathogenesis, genetics and treatment. Pediatr Nephrol. 1992 Sep;6(5):476–482. doi: 10.1007/BF00874020. [DOI] [PubMed] [Google Scholar]
  14. Knoers N., Van Lieburg A. F., Monnens L. A., Van Oost B. A., Deen P. M., Van Os C. Aquaporins: from physiology to nephrogenic diabetes insipidus. Adv Nephrol Necker Hosp. 1996;25:257–273. [PubMed] [Google Scholar]
  15. Libber S., Harrison H., Spector D. Treatment of nephrogenic diabetes insipidus with prostaglandin synthesis inhibitors. J Pediatr. 1986 Feb;108(2):305–311. doi: 10.1016/s0022-3476(86)81010-1. [DOI] [PubMed] [Google Scholar]
  16. Macaulay D., Watson M. Hypernatraemia in infants as a cause of brain damage. Arch Dis Child. 1967 Oct;42(225):485–491. doi: 10.1136/adc.42.225.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McMahon F. G., Ryan J. R., Akdamar K., Ertan A. Upper gastrointestinal lesions after potassium chloride supplements: a controlled clinical trial. Lancet. 1982 Nov 13;2(8307):1059–1061. doi: 10.1016/s0140-6736(82)90002-2. [DOI] [PubMed] [Google Scholar]
  18. Monn E. Prostaglandin synthetase inhibitors in the treatment of nephrogenic diabetes insipidus. Acta Paediatr Scand. 1981 Jan;70(1):39–42. doi: 10.1111/j.1651-2227.1981.tb07170.x. [DOI] [PubMed] [Google Scholar]
  19. Morgan D. B., Davidson C. Hypokalaemia and diuretics: an analysis of publications. Br Med J. 1980 Mar 29;280(6218):905–908. doi: 10.1136/bmj.280.6218.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nozue T., Uemasu F., Endoh H., Sako A., Takagi Y., Kobayashi A. Intracranial calcifications associated with nephrogenic diabetes insipidus. Pediatr Nephrol. 1993 Feb;7(1):74–76. doi: 10.1007/BF00861577. [DOI] [PubMed] [Google Scholar]
  21. Rosenthal W., Seibold A., Antaramian A., Lonergan M., Arthus M. F., Hendy G. N., Birnbaumer M., Bichet D. G. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature. 1992 Sep 17;359(6392):233–235. doi: 10.1038/359233a0. [DOI] [PubMed] [Google Scholar]
  22. Schofer O., Beetz R., Bohl J., Bornemann A., Oepen J., Spranger J. Mental retardation syndrome with renal concentration deficiency and intracerebral calcification. Eur J Pediatr. 1990 Apr;149(7):470–474. doi: 10.1007/BF01959397. [DOI] [PubMed] [Google Scholar]
  23. Schofer O., Beetz R., Kruse K., Rascher C., Schütz C., Bohl J. Nephrogenic diabetes insipidus and intracerebral calcification. Arch Dis Child. 1990 Aug;65(8):885–887. doi: 10.1136/adc.65.8.885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Stevens S., Brown B. D., McGahan J. P. Nephrogenic diabetes insipidus: a cause of severe nonobstructive urinary tract dilatation. J Ultrasound Med. 1995 Jul;14(7):543–545. doi: 10.7863/jum.1995.14.7.543. [DOI] [PubMed] [Google Scholar]
  25. Tohyama J., Inagaki M., Koeda T., Ohno K., Takeshita K. Intracranial calcification in siblings with nephrogenic diabetes insipidus: CT and MRI. Neuroradiology. 1993;35(7):553–555. doi: 10.1007/BF00588723. [DOI] [PubMed] [Google Scholar]
  26. Uribarri J., Kaskas M. Hereditary nephrogenic diabetes insipidus and bilateral nonobstructive hydronephrosis. Nephron. 1993;65(3):346–349. doi: 10.1159/000187510. [DOI] [PubMed] [Google Scholar]
  27. Uyeki T. M., Barry F. L., Rosenthal S. M., Mathias R. S. Successful treatment with hydrochlorothiazide and amiloride in an infant with congenital nephrogenic diabetes insipidus. Pediatr Nephrol. 1993 Oct;7(5):554–556. doi: 10.1007/BF00852546. [DOI] [PubMed] [Google Scholar]
  28. van Lieburg A. F., Knoers N. V., Deen P. M. Discovery of aquaporins: a breakthrough in research on renal water transport. Pediatr Nephrol. 1995 Apr;9(2):228–234. doi: 10.1007/BF00860757. [DOI] [PubMed] [Google Scholar]
  29. van Lieburg A. F., Verdijk M. A., Knoers V. V., van Essen A. J., Proesmans W., Mallmann R., Monnens L. A., van Oost B. A., van Os C. H., Deen P. M. Patients with autosomal nephrogenic diabetes insipidus homozygous for mutations in the aquaporin 2 water-channel gene. Am J Hum Genet. 1994 Oct;55(4):648–652. [PMC free article] [PubMed] [Google Scholar]
  30. van Lieburg A. F., Verdijk M. A., Schoute F., Ligtenberg M. J., van Oost B. A., Waldhauser F., Dobner M., Monnens L. A., Knoers N. V. Clinical phenotype of nephrogenic diabetes insipidus in females heterozygous for a vasopressin type 2 receptor mutation. Hum Genet. 1995 Jul;96(1):70–78. doi: 10.1007/BF00214189. [DOI] [PubMed] [Google Scholar]

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