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Nephrogenic diabetes insipidus: a comprehensive overview

  • Pedro Alves Soares Vaz de Castro , Letícia Bitencourt , Juliana Lacerda de Oliveira Campos , Bruna Luisa Fischer , Stephanie Bruna Camilo Soares de Brito , Beatriz Santana Soares , Juliana Beaudette Drummond and Ana Cristina Simões e Silva ORCID logo EMAIL logo
Published/Copyright: February 11, 2022
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 35 Issue 4

Abstract

Nephrogenic diabetes insipidus (NDI) is characterized by the inability to concentrate urine that results in polyuria and polydipsia, despite having normal or elevated plasma concentrations of arginine vasopressin (AVP). In this study, we review the clinical aspects and diagnosis of NDI, the various etiologies, current treatment options and potential future developments. NDI has different clinical manifestations and approaches according to the etiology. Hereditary forms of NDI are mainly caused by mutations in the genes that encode key proteins in the AVP signaling pathway, while acquired causes are normally associated with specific drug exposure, especially lithium, and hydroelectrolytic disorders. Clinical manifestations of the disease vary according to the degree of dehydration and hyperosmolality, being worse when renal water losses cannot be properly compensated by fluid intake. Regarding the diagnosis of NDI, it is important to consider the symptoms of the patient and the diagnostic tests, including the water deprivation test and the baseline plasma copeptin measurement, a stable surrogate biomarker of AVP release. Without proper treatment, patients may developcomplications leading to high morbidity and mortality, such as severe dehydration and hypernatremia. In that sense, the treatment of NDI consists in decreasing the urine output, while allowing appropriate fluid balance, normonatremia, and ensuring an acceptable quality of life. Therefore, therapeutic options include nonpharmacological interventions, including sufficient water intake and a low-sodium diet, and pharmacological treatment. The main medications used for NDI are thiazide diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and amiloride, used isolated or in combination.

Keywords: arginine vasopressin; copeptin; diuretics; nephrogenic diabetes insipidus; polyuria-polydipsia syndrome; water deprivation test
Corresponding author: Ana Cristina Simões e Silva, MD, PhD, Professor of Pediatrics, Coordinator of the Pediatric Nephrology Unit, Interdisciplinary Laboratory of Medical Investigation, Unit of Pediatric Nephrology, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2nd floor, room #281, Belo Horizonte, 30130-100, Minas Gerais, Brazil, E-mail: .
Pedro Alves Soares Vaz de Castro and Letícia Bitencourt contributed equally as first authors.

  1. Research funding: This work was partially supported by Brazilian National Council of Research Development (CNPq – Grant # 302153/2019-5).

  2. Author contribution: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: not applicable.

  5. Ethical approval: The local Institutional Review Board deemed the study exempt from review.

References

1. Kavanagh, C, Uy, NS. Nephrogenic diabetes insipidus. Pediatr Clin 2019;66:227–34. https://doi.org/10.1016/j.pcl.2018.09.006.Search in Google Scholar PubMed

2. Christ-Crain, M, Bichet, DG, Fenske, WK, Goldman, MB, Rittig, S, Verbalis, JG, et al.. Diabetes insipidus. Nat Rev Dis Prim 2019;5:54. https://doi.org/10.1038/s41572-019-0103-2.Search in Google Scholar PubMed

3. D’Alessandri-Silva, C, Carpenter, M, Ayoob, R, Barcia, J, Chishti, A, Constantinescu, A, et al.. Diagnosis, treatment, and outcomes in children with congenital nephrogenic diabetes insipidus: a pediatric nephrology research consortium study. Front Pediatr 2020;7:550. https://doi.org/10.3389/fped.2019.00550.Search in Google Scholar PubMed PubMed Central

4. Bichet, DG. Genetics in endocrinology pathophysiology, diagnosis and treatment of familial nephrogenic diabetes insipidus. Eur J Endocrinol 2020;183:R29–40. https://doi.org/10.1530/EJE-20-0114.Search in Google Scholar PubMed

5. Birnbaumer, M, Seibold, A, Gilbert, S, Ishido, M, Barberis, C, Antaramian, A, et al.. Molecular cloning of the receptor for human antidiuretic hormone. Nature 1992;357:333–5. https://doi.org/10.1038/357333a0.Search in Google Scholar PubMed

6. Namatame-Ohta, N, Morikawa, S, Nakamura, A, Matsuo, K, Nakajima, M, Tomizawa, K, et al.. Four Japanese patients with congenital nephrogenic diabetes insipidus due to the AVPR2 mutations. Case Rep Pediatr 2018;2018:1–6. https://doi.org/10.1155/2018/6561952.Search in Google Scholar PubMed PubMed Central

7. Bockenhauer, D, Bichet, DG. Pathophysiology, diagnosis and management of nephrogenic diabetes insipidus. Nat Rev Nephrol 2015;11:576–88. https://doi.org/10.1038/nrneph.2015.89.Search in Google Scholar PubMed

8. Milano, S, Carmosino, M, Gerbino, A, Svelto, M, Procino, G. Hereditary nephrogenic diabetes insipidus: pathophysiology and possible treatment. An update. Int J Mol Sci 2017;18:2385. https://doi.org/10.3390/ijms18112385.Search in Google Scholar PubMed PubMed Central

9. Mamenko, M, Dhande, I, Tomilin, V, Zaika, O, Boukelmoune, N, Zhu, Y, et al.. Defective store-operated calcium entry causes partial nephrogenic diabetes insipidus. J Am Soc Nephrol 2016;27:2035–48. https://doi.org/10.1681/ASN.2014121200.Search in Google Scholar PubMed PubMed Central

10. Rosenthal, W, Seibold, A, Antaramian, A, Lonergan, M, Arthus, M-F, Hendy, GN, et al.. Molecular identification of the gene responsible for congenital nephrogenic diabetes insipidus. Nature 1992;359:233–5. https://doi.org/10.1038/359233a0.Search in Google Scholar PubMed

11. Arthus, MF, Lonergan, M, Crumley, MJ, Naumova, AK, Morin, D, De Marco, LA, et al.. Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 2000;11:1044–54. https://doi.org/10.1681/ASN.V1161044.Search in Google Scholar

12. Moeller, HB, Rittig, S, Fenton, RA. Nephrogenic diabetes insipidus: essential insights into the molecular background and potential therapies for treatment. Endocr Rev 2013;34:278–301. https://doi.org/10.1210/er.2012-1044.Search in Google Scholar

13. Bichet, DG, Bockenhauer, D. Genetic forms of nephrogenic diabetes insipidus (NDI): vasopressin receptor defect (X-linked) and aquaporin defect (autosomal recessive and dominant). Best Pract Res Clin Endocrinol Metabol 2016;30:263–76. https://doi.org/10.1016/j.beem.2016.02.010.Search in Google Scholar

14. Robben, JH, Knoers, NVAM, Deen, PMT. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Ren Physiol 2006;291:F257–270. https://doi.org/10.1152/ajprenal.00491.2005.Search in Google Scholar

15. Ellgaard, L, Helenius, A. ER quality control: towards an understanding at the molecular level. Curr Opin Cell Biol 2001;13:431–7. https://doi.org/10.1016/s0955-0674(00)00233-7.Search in Google Scholar

16. Barak, LS, Oakley, RH, Laporte, SA, Caron, MG. Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus. Proc Natl Acad Sci U S A 2001;98:93–8. https://doi.org/10.1073/pnas.011303698.Search in Google Scholar

17. Morello, J-P, Bichet, DG. Nephrogenic diabetes insipidus. Annu Rev Physiol 2001;63:607–30. https://doi.org/10.1146/annurev.physiol.63.1.607.Search in Google Scholar PubMed

18. de Mattia, F, Savelkoul, PJM, Kamsteeg, E-J, Konings, IBM, van der Sluijs, P, Mallmann, R, et al.. Lack of arginine vasopressin–induced phosphorylation of aquaporin-2 mutant AQP2-R254L explains dominant nephrogenic diabetes insipidus. J Am Soc Nephrol 2005;16:2872–80. https://doi.org/10.1681/ASN.2005010104.Search in Google Scholar PubMed

19. Christensen, BM, Marples, D, Kim, Y-H, Wang, W, Frøkiær, J, Nielsen, S. Changes in cellular composition of kidney collecting duct cells in rats with lithium-induced NDI. Am J Physiol Cell Physiol 2004;286:C952–64. https://doi.org/10.1152/ajpcell.00266.2003.Search in Google Scholar PubMed

20. Gong, R, Wang, P, Dworkin, L. What we need to know about the effect of lithium on the kidney. Am J Physiol Ren Physiol 2016;311:F1168–71. https://doi.org/10.1152/ajprenal.00145.2016.Search in Google Scholar PubMed PubMed Central

21. Kortenoeven, MLA, Li, Y, Shaw, S, Gaeggeler, H-P, Rossier, BC, Wetzels, JFM, et al.. Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus. Kidney Int 2009;76:44–53. https://doi.org/10.1038/ki.2009.91.Search in Google Scholar PubMed

22. Grünfeld, J-P, Rossier, BC. Lithium nephrotoxicity revisited. Nat Rev Nephrol 2009;5:270–6. https://doi.org/10.1038/nrneph.2009.43.Search in Google Scholar PubMed

23. Rao, R. Glycogen synthase kinase-3 regulation of urinary concentrating ability. Curr Opin Nephrol Hypertens 2012;21:541–6. https://doi.org/10.1097/MNH.0b013e32835571d4.Search in Google Scholar PubMed PubMed Central

24. Marples, D, Christensen, S, Christensen, EI, Ottosen, PD, Nielsen, S. Lithium-induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 1995;95:1838–45. https://doi.org/10.1172/JCI117863.Search in Google Scholar PubMed PubMed Central

25. Khositseth, S, Charngkaew, K, Boonkrai, C, Somparn, P, Uawithya, P, Chomanee, N, et al.. Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus. Kidney Int 2017;91:1070–87. https://doi.org/10.1016/j.kint.2016.12.005.Search in Google Scholar PubMed

26. Khositseth, S, Uawithya, P, Somparn, P, Charngkaew, K, Thippamom, N, Hoffert, JD, et al.. Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus. Sci Rep 2015;5:18311. https://doi.org/10.1038/srep18311.Search in Google Scholar PubMed PubMed Central

27. Elkjaer, M-L, Kwon, T-H, Wang, W, Nielsen, J, Knepper, MA, Frøkiaer, J, et al.. Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats. Am J Physiol Ren Physiol 2002;283:F1376–1388. https://doi.org/10.1152/ajprenal.00186.2002.Search in Google Scholar PubMed

28. Wang, W, Kwon, T-H, Li, C, Frøkiaer, J, Knepper, MA, Nielsen, S. Reduced expression of Na-K-2Cl cotransporter in medullary TAL in vitamin D-induced hypercalcemia in rats. Am J Physiol Ren Physiol 2002;282:F34–44. https://doi.org/10.1152/ajprenal.0101.2001.Search in Google Scholar PubMed

29. Bockenhauer, D, Bichet, DG. Inherited secondary nephrogenic diabetes insipidus: concentrating on humans. Am J Physiol Ren Physiol 2013;304:F1037–1042. https://doi.org/10.1152/ajprenal.00639.2012.Search in Google Scholar PubMed

30. Li, Q, Tian, D, Cen, J, Duan, L, Xia, W. Novel AVPR2 mutations and clinical characteristics in 28 Chinese families with congenital nephrogenic diabetes insipidus. J Endocrinol Invest 2021;44:2777–83. https://doi.org/10.1007/s40618-021-01607-3.Search in Google Scholar PubMed

31. Bockenhauer, D, Bichet, DG. Nephrogenic diabetes insipidus. Curr Opin Pediatr 2017;29:199–205. https://doi.org/10.1097/MOP.0000000000000473.Search in Google Scholar PubMed

32. Di Iorgi, N, Napoli, F, Allegri, AEM, Olivieri, I, Bertelli, E, Gallizia, A, et al.. Diabetes insipidus--diagnosis and management. Horm Res Paediatr 2012;77:69–84. https://doi.org/10.1159/000336333.Search in Google Scholar PubMed

33. Gubbi, S, Hannah-Shmouni, F, Koch, CA, Verbalis, JG. Diagnostic testing for diabetes insipidus. In: Feingold, KR, Anawalt, B, Boyce, A, Chrousos, G, de Herder, WW, Dhatariya, K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000. [cited 2021 Apr 27]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK537591/.Search in Google Scholar

34. Christ-Crain, M. Diabetes insipidus: new concepts for diagnosis. Neuroendocrinology 2020;110:859–67. https://doi.org/10.1159/000505548.Search in Google Scholar PubMed

35. Lu, HAJ. Diabetes insipidus. Adv Exp Med Biol 2017;969:213–25. https://doi.org/10.1007/978-94-024-1057-0_14.Search in Google Scholar PubMed

36. Miller, M. Recognition of partial defects in antidiuretic hormone secretion. Ann Intern Med 1970;73:721. https://doi.org/10.7326/0003-4819-73-5-721.Search in Google Scholar PubMed

37. Fenske, W, Quinkler, M, Lorenz, D, Zopf, K, Haagen, U, Papassotiriou, J, et al.. Copeptin in the differential diagnosis of the polydipsia-polyuria syndrome—revisiting the direct and indirect water deprivation tests. J Clin Endocrinol Metab 2011;96:1506–15. https://doi.org/10.1210/jc.2010-2345.Search in Google Scholar PubMed

38. Christ-Crain, M, Fenske, W. Copeptin in the diagnosis of vasopressin-dependent disorders of fluid homeostasis. Nat Rev Endocrinol 2016;12:168–76. https://doi.org/10.1038/nrendo.2015.224.Search in Google Scholar PubMed

39. Gellai, M, Edwards, BR, Valtin, H. Urinary concentrating ability during dehydration in the absence of vasopressin. Am J Physiol Ren Physiol 1979;237:F100–4. https://doi.org/10.1152/ajprenal.1979.237.2.F100.Search in Google Scholar PubMed

40. Edwards, BR, LaRochelle, FT. Antidiuretic effect of endogenous oxytocin in dehydrated Brattleboro homozygous rats. Am J Physiol 1984;247:F453–465. https://doi.org/10.1152/ajprenal.1984.247.3.F453.Search in Google Scholar PubMed

41. Zerbe, RL, Robertson, GL. A comparison of plasma vasopressin measurements with a standard indirect test in the differential diagnosis of polyuria. N Engl J Med 1981;305:1539–46. https://doi.org/10.1056/NEJM198112243052601.Search in Google Scholar PubMed

42. Refardt, J, Winzeler, B, Christ-Crain, M. Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis. Clin Endocrinol 2019;91:22–32. https://doi.org/10.1111/cen.13991.Search in Google Scholar PubMed PubMed Central

43. Fenske, W, Refardt, J, Chifu, I, Schnyder, I, Winzeler, B, Drummond, J, et al.. A copeptin-based approach in the diagnosis of diabetes insipidus. N Engl J Med 2018;379:428–39. https://doi.org/10.1056/NEJMoa1803760.Search in Google Scholar PubMed

44. Christ-Crain, M, Fenske, WK. Copeptin in the differential diagnosis of hypotonic polyuria. J Endocrinol Invest 2020;43:21–30. https://doi.org/10.1007/s40618-019-01087-6.Search in Google Scholar PubMed

45. Tuli, G, Tessaris, D, Einaudi, S, Matarazzo, P, De Sanctis, L. Copeptin role in polyuria-polydipsia syndrome differential diagnosis and reference range in paediatric age. Clin Endocrinol 2018;88:873–9. https://doi.org/10.1111/cen.13583.Search in Google Scholar PubMed

46. Bonnet, L, Marquant, E, Fromonot, J, Hamouda, I, Berbis, J, Godefroy, A, et al.. Copeptin assays in children for the differential diagnosis of polyuria-polydipsia syndrome and reference levels in hospitalized children. Clin Endocrinol 2022;96:47–53. https://doi.org/10.1111/cen.14620.Search in Google Scholar PubMed

47. Balanescu, S, Kopp, P, Gaskill, MB, Morgenthaler, NG, Schindler, C, Rutishauser, J. Correlation of plasma copeptin and vasopressin concentrations in hypo-, iso-, and hyperosmolar states. J Clin Endocrinol Metab 2011;96:1046–52. https://doi.org/10.1210/jc.2010-2499.Search in Google Scholar PubMed

48. Timper, K, Fenske, W, Kühn, F, Frech, N, Arici, B, Rutishauser, J, et al.. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. J Clin Endocrinol Metab 2015;100:2268–74. https://doi.org/10.1210/jc.2014-4507.Search in Google Scholar PubMed

49. Bitencourt, L, Fischer, BL, de Oliveira Campos, JL, Vaz de Castro, PAS, Soares de Brito, SBC, Versiani, CM, et al.. The usefulness of copeptin for the diagnosis of nephrogenic diabetes insipidus in infancy: a case report. J Pediatr Endocrinol Metab 2021;34:1475–9. https://doi.org/10.1515/jpem-2021-0296.Search in Google Scholar PubMed

50. Roussel, R, Fezeu, L, Marre, M, Velho, G, Fumeron, F, Jungers, P, et al.. Comparison between copeptin and vasopressin in a population from the community and in people with chronic kidney disease. J Clin Endocrinol Metab 2014;99:4656–63. https://doi.org/10.1210/jc.2014-2295.Search in Google Scholar PubMed

51. Atmis, B, Bayazit, AK, Melek, E, Bisgin, A, Anarat, A. From infancy to adulthood: challenges in congenital nephrogenic diabetes insipidus. J Pediatr Endocrinol Metab 2020;33:1019–25. https://doi.org/10.1515/jpem-2019-0529.Search in Google Scholar PubMed

52. Dabrowski, E, Kadakia, R, Zimmerman, D. Diabetes insipidus in infants and children. Best Pract Res Clin Endocrinol Metabol 2016;30:317–28. https://doi.org/10.1016/j.beem.2016.02.006.Search in Google Scholar

53. Crawford, JD, Kennedy, GC. Chlorothiazid in diabetes insipidus. Nature 1959;183:891–2. https://doi.org/10.1038/183891a0.Search in Google Scholar

54. Bouley, R, Hasler, U, Lu, HAJ, Nunes, P, Brown, D. Bypassing vasopressin receptor signaling pathways in nephrogenic diabetes insipidus. Semin Nephrol 2008;28:266–78. https://doi.org/10.1016/j.semnephrol.2008.03.010.Search in Google Scholar

55. Alon, U, Chan, JC. Hydrochlorothiazide-amiloride in the treatment of congenital nephrogenic diabetes insipidus. Am J Nephrol 1985;5:9–13. https://doi.org/10.1159/000166896.Search in Google Scholar

56. Bedford, JJ, Weggery, S, Ellis, G, McDonald, FJ, Joyce, PR, Leader, JP, et al.. Lithium-induced nephrogenic diabetes insipidus: renal effects of amiloride. Clin J Am Soc Nephrol 2008;3:1324–31. https://doi.org/10.2215/CJN.01640408.Search in Google Scholar

57. Feig, PU. Cellular mechanism of action of loop diuretics: implications for drug effectiveness and adverse effects. Am J Cardiol 1986;57:14A–19A. https://doi.org/10.1016/0002-9149(86)91001-5.Search in Google Scholar

58. de Groot, T, Sinke, AP, Kortenoeven, MLA, Alsady, M, Baumgarten, R, Devuyst, O, et al.. Acetazolamide attenuates lithium-induced nephrogenic diabetes insipidus. J Am Soc Nephrol 2016;27:2082–91. https://doi.org/10.1681/ASN.2015070796.Search in Google Scholar PubMed PubMed Central

59. Levenson, E, Shepherd, TN, Aviles, D, Craver, R, Ehlayel, A, Love, GL, et al.. De novo collapsing glomerulopathy in a pediatric kidney transplant recipient with COVID-19 infection. Pediatr Transplant 2021;25:e14013. https://doi.org/10.1111/petr.14013.Search in Google Scholar PubMed

60. Ott, M, Forssén, B, Werneke, U. Lithium treatment, nephrogenic diabetes insipidus and the risk of hypernatraemia: a retrospective cohort study. Ther Adv Psychopharmacol 2019;9. https://doi.org/10.1177/2045125319836563.Search in Google Scholar PubMed PubMed Central

61. Kim, G-H, Choi, NW, Jung, J-Y, Song, J-H, Lee, CH, Kang, CM, et al.. Treating lithium-induced nephrogenic diabetes insipidus with a COX-2 inhibitor improves polyuria via upregulation of AQP2 and NKCC2. Am J Physiol Ren Physiol 2008;294:F702–709. https://doi.org/10.1152/ajprenal.00366.2007.Search in Google Scholar PubMed

62. Li, Y, Wei, Y, Zheng, F, Guan, Y, Zhang, X. Prostaglandin E2 in the regulation of water transport in renal collecting ducts. Int J Mol Sci 2017;18:2539. https://doi.org/10.3390/ijms18122539.Search in Google Scholar

63. Kramer, HJ, Glänzer, K, Düsing, R. Role of prostaglandins in the regulation of renal water excretion. Kidney Int 1981;19:851–9. https://doi.org/10.1038/ki.1981.89.Search in Google Scholar

64. Kim, GH, Ecelbarger, CA, Mitchell, C, Packer, RK, Wade, JB, Knepper, MA. Vasopressin increases Na-K-2Cl cotransporter expression in thick ascending limb of Henle’s loop. Am J Physiol 1999;276:F96–103. https://doi.org/10.1152/ajprenal.1999.276.1.F96.Search in Google Scholar

65. Moses, AM, Scheinman, SJ, Schroeder, ET. Antidiuretic and PGE2 responses to AVP and dDAVP in subjects with central and nephrogenic diabetes insipidus. Am J Physiol 1985;248:F354–359. https://doi.org/10.1152/ajprenal.1985.248.3.F354.Search in Google Scholar

66. Hochberg, Z, Even, L, Danon, A. Amelioration of polyuria in nephrogenic diabetes insipidus due to aquaporin-2 deficiency. Clin Endocrinol 1998;49:39–44. https://doi.org/10.1046/j.1365-2265.1998.00426.x.Search in Google Scholar

67. Hober, C, Vantyghem, MC, Racadot, A, Cappoen, JP, Lefebvre, J. Normal hemodynamic and coagulation responses to 1-deamino-8-D-arginine vasopressin in a case of lithium-induced nephrogenic diabetes insipidus. Results of treatment by a prostaglandin synthesis inhibitor (indomethacin). Horm Res 1992;37:190–5. https://doi.org/10.1159/000182308.Search in Google Scholar

68. Libber, S, Harrison, H, Spector, D. Treatment of nephrogenic diabetes insipidus with prostaglandin synthesis inhibitors. J Pediatr 1986;108:305–11. https://doi.org/10.1016/s0022-3476(86)81010-1.Search in Google Scholar

69. Boussemart, T, Nsota, J, Martin-Coignard, D, Champion, G. Nephrogenic diabetes insipidus: treat with caution. Pediatr Nephrol 2009;24:1761–3. https://doi.org/10.1007/s00467-009-1187-9.Search in Google Scholar PubMed

70. Mizuno, H, Fujimoto, S, Sugiyama, Y, Kobayashi, M, Ohro, Y, Uchida, S, et al.. Successful treatment of partial nephrogenic diabetes insipidus with thiazide and desmopressin. Horm Res 2003;59:297–300. https://doi.org/10.1159/000070629.Search in Google Scholar PubMed

71. Soylu, A, Kasap, B, Oğün, N, Oztürk, Y, Türkmen, M, Hoefsloot, L, et al.. Efficacy of COX-2 inhibitors in a case of congenital nephrogenic diabetes insipidus. Pediatr Nephrol 2005;20:1814–7. https://doi.org/10.1007/s00467-005-2057-8.Search in Google Scholar PubMed

72. Sands, JM, Klein, JD. Physiological insights into novel therapies for nephrogenic diabetes insipidus. Am J Physiol Ren Physiol 2016;311:F1149–52. https://doi.org/10.1152/ajprenal.00418.2016.Search in Google Scholar PubMed PubMed Central

73. Bouley, R, Pastor-Soler, N, Cohen, O, McLaughlin, M, Breton, S, Brown, D. Stimulation of AQP2 membrane insertion in renal epithelial cells in vitro and in vivo by the cGMP phosphodiesterase inhibitor sildenafil citrate (Viagra). Am J Physiol Ren Physiol 2005;288:F1103–1112. https://doi.org/10.1152/ajprenal.00337.2004.Search in Google Scholar PubMed

74. Li, W, Zhang, Y, Bouley, R, Chen, Y, Matsuzaki, T, Nunes, P, et al.. Simvastatin enhances aquaporin-2 surface expression and urinary concentration in vasopressin-deficient Brattleboro rats through modulation of Rho GTPase. Am J Physiol Ren Physiol 2011;301:F309–318. https://doi.org/10.1152/ajprenal.00001.2011.Search in Google Scholar PubMed PubMed Central

75. Bech, AP, Wetzels, JFM, Nijenhuis, T. Effects of sildenafil, metformin, and simvastatin on ADH-independent urine concentration in healthy volunteers. Phys Rep 2018;6:e13665. https://doi.org/10.14814/phy2.13665.Search in Google Scholar PubMed PubMed Central

76. Bouley, R, Lu, HAJ, Nunes, P, Da Silva, N, McLaughlin, M, Chen, Y, et al.. Calcitonin has a vasopressin-like effect on aquaporin-2 trafficking and urinary concentration. J Am Soc Nephrol 2011;22:59–72. https://doi.org/10.1681/ASN.2009121267.Search in Google Scholar PubMed PubMed Central

77. Ando, F, Uchida, S. Activation of AQP2 water channels without vasopressin: therapeutic strategies for congenital nephrogenic diabetes insipidus. Clin Exp Nephrol 2018;22:501–7. https://doi.org/10.1007/s10157-018-1544-8.Search in Google Scholar PubMed PubMed Central

78. Bichet, DG, Ruel, N, Arthus, MF, Lonergan, M. Rolipram, a phosphodiesterase inhibitor, in the treatment of two male patients with congenital nephrogenic diabetes insipidus. Nephron. 1990;56:449–50. https://doi.org/10.1159/000186196.Search in Google Scholar PubMed

79. Tingskov, SJ, Hu, S, Frøkiær, J, Kwon, T-H, Wang, W, Nørregaard, R. Tamoxifen attenuates development of lithium-induced nephrogenic diabetes insipidus in rats. Am J Physiol Ren Physiol 2018;314:F1020–5. https://doi.org/10.1152/ajprenal.00604.2017.Search in Google Scholar PubMed

80. Tingskov, SJ, Choi, H-J, Holst, MR, Hu, S, Li, C, Wang, W, et al.. Vasopressin-independent regulation of aquaporin-2 by tamoxifen in kidney collecting ducts. Front Physiol 2019;10:948. https://doi.org/10.3389/fphys.2019.00948.Search in Google Scholar PubMed PubMed Central

81. Vukićević, T, Hinze, C, Baltzer, S, Himmerkus, N, Quintanova, C, Zühlke, K, et al.. Fluconazole increases osmotic water transport in renal collecting duct through effects on aquaporin-2 trafficking. J Am Soc Nephrol 2019;30:795–810. https://doi.org/10.1681/ASN.2018060668.Search in Google Scholar PubMed PubMed Central

82. Zhang, Y, Peti-Peterdi, J, Heiney, KM, Riquier-Brison, A, Carlson, NG, Müller, CE, et al.. Clopidogrel attenuates lithium-induced alterations in renal water and sodium channels/transporters in mice. Purinergic Signal 2015;11:507–18. https://doi.org/10.1007/s11302-015-9469-0.Search in Google Scholar

83. Erdem Tuncdemir, B, Mergen, H, Saglar Ozer, E. Evaluation of pharmacochaperone-mediated rescue of mutant V2 receptor proteins. Eur J Pharmacol 2019;865:172803. https://doi.org/10.1016/j.ejphar.2019.172803.Search in Google Scholar

84. Robben, JH, Sze, M, Knoers, NVaM, Deen, PMT. Functional rescue of vasopressin V2 receptor mutants in MDCK cells by pharmacochaperones: relevance to therapy of nephrogenic diabetes insipidus. Am J Physiol Ren Physiol 2007;292:F253–260. https://doi.org/10.1152/ajprenal.00247.2006.Search in Google Scholar

85. Beerepoot, P, Nazari, R, Salahpour, A. Pharmacological chaperone approaches for rescuing GPCR mutants: current state, challenges, and screening strategies. Pharmacol Res 2017;117:242–51. https://doi.org/10.1016/j.phrs.2016.12.036.Search in Google Scholar

86. Bernier, V, Morello, J-P, Zarruk, A, Debrand, N, Salahpour, A, Lonergan, M, et al.. Pharmacologic chaperones as a potential treatment for X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol 2006;17:232–43. https://doi.org/10.1681/ASN.2005080854.Search in Google Scholar

87. Yang, B, Zhao, D, Verkman, AS. Hsp90 inhibitor partially corrects nephrogenic diabetes insipidus in a conditional knock-in mouse model of aquaporin-2 mutation. Fed Am Soc Exp Biol 2009;23:503–12. https://doi.org/10.1073/pnas.080499597.Search in Google Scholar

88. Olesen, ETB, Rützler, MR, Moeller, HB, Praetorius, HA, Fenton, RA. Vasopressin-independent targeting of aquaporin-2 by selective E-prostanoid receptor agonists alleviates nephrogenic diabetes insipidus. Proc Natl Acad Sci U S A 2011;108:12949–54. https://doi.org/10.1073/pnas.1104691108.Search in Google Scholar

89. Procino, G, Carmosino, M, Milano, S, Dal Monte, M, Schena, G, Mastrodonato, M, et al.. β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function. Kidney Int 2016;90:555–67. https://doi.org/10.1016/j.kint.2016.03.020.Search in Google Scholar

90. Inoue, M, Suga, H, Nagasaki, H, Kondo, T, Hasegawa, M, Oiso, Y. Gene therapy for nephrogenic diabetes insipidus: renal medulla targeted Aquaporin2 expression by Sendai-virus vector rescued polyurea in rat models. Mol Ther 2008;16:S370. https://doi.org/10.1016/S1525-0016(16)40390-4.Search in Google Scholar

91. Yoshida, M, Iwasaki, Y, Asai, M, Nigawara, T, Oiso, Y. Gene therapy for central diabetes insipidus: effective antidiuresis by muscle-targeted gene transfer. Endocrinology 2004;145:261–8. https://doi.org/10.1210/en.2003-0366.Search in Google Scholar PubMed

Received: 2021-08-31
Accepted: 2022-01-26
Published Online: 2022-02-11
Published in Print: 2022-04-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Nephrogenic diabetes insipidus: a comprehensive overview
  4. Original Articles
  5. Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
  6. Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
  7. Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
  8. Evaluation of patients with phenylalanine metabolism disorder: a single center experience
  9. The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
  10. Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
  11. Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
  12. Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
  13. Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in FBP1
  14. Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
  15. Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
  16. Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
  17. Letter to the Editor
  18. Correspondence on “Obesity after the Covid-19 pandemic”
  19. Case Reports
  20. An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
  21. Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
  22. Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
  23. Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
https://doi.org/10.1515/jpem-2021-0566
Keywords for this article
arginine vasopressin; copeptin; diuretics; nephrogenic diabetes insipidus; polyuria-polydipsia syndrome; water deprivation test

Articles in the same Issue

  1. Frontmatter
  2. Review Article
  3. Nephrogenic diabetes insipidus: a comprehensive overview
  4. Original Articles
  5. Prevalence of type 2 diabetes mellitus, metabolic syndrome, and related morbidities in overweight and obese children
  6. Impact of sports participation on components of metabolic syndrome in adolescents: ABCD growth study
  7. Expected or unexpected clinical findings in liver glycogen storage disease type IX: distinct clinical and molecular variability
  8. Evaluation of patients with phenylalanine metabolism disorder: a single center experience
  9. The association of grandparental co-residence and dietary knowledge with excess body weight among children aged 7–15 years in China
  10. Clinical characteristics of polyglandular autoimmune syndromes in pediatric age: an observational study
  11. Serum kisspeptin, leptin, neuropeptide Y, and neurokinin B levels in adolescents with polycystic ovary syndrome
  12. Ultrasonographic measurements of the testicular volume in Turkish boys aged 0–8 years and comparison with international references
  13. Fructose 1,6 bisphosphatase deficiency: outcomes of patients in a single center in Turkey and identification of novel splice site and indel mutations in FBP1
  14. Benefits of metformin add-on insulin therapy (MAIT) for HbA1c and lipid profile in adolescents with type 1 diabetes mellitus: preliminary report from a double-blinded, placebo-controlled, randomized clinical trial
  15. Evaluation of efficacy and safety of long-acting PEGylated recombinant human growth hormone (Jintrolong) for patients with growth hormone deficiency
  16. Evaluation of endocrinological involvement and metabolic status in patients with Gaucher disease Type 1 and Fabry disease under enzyme replacement therapy
  17. Letter to the Editor
  18. Correspondence on “Obesity after the Covid-19 pandemic”
  19. Case Reports
  20. An unusual presentation of primary adrenal insufficiency with new onset type 1 diabetes: case report and review of the literature
  21. Niemann–Pick type C disease with a novel intronic mutation: three Turkish cases from the same family
  22. Weight management in youth with rapid-onset obesity with hypothalamic dysregulation, hypoventilation, autonomic dysregulation, and neural crest tumor (ROHHAD-NET): literature search and case report
  23. Successful use of cinacalcet monotherapy in the management of siblings with homozygous calcium-sensing receptor mutation
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