Abstract
Background
Tolvaptan is a selective oral vasopressin V2-receptor antagonist. Some data have implicated stimulation of arginine vasopressin (AVP) as an important factor in oedema formation in a rodent model of nephrotic syndrome (NS) and adult NS patients. We report case of pediatric NS with severe hyponatremia efficiently treated by tolvaptan.
Case/diagnosis – Treatment
A 22-month-old girl presented first with NS. She remained nephrotic after a 30-day course of oral steroids. Tacrolimus was inefficient and there was no response to plasma exchanges (15 sessions on a daily basis). She had severe oedema and ascites. Thus, in addition to immunosuppressive therapy, she received diuretics, furosemide 5 mg/kg/day, and amiloride 1 mg/kg/day, and required water restriction. She was hypertensive and was treated with a full dose of calcium inhibitor (amlodipine 0.5 mg/kg/day). After2 months of treatment, serum sodium reached 116 mmol/L and urinary osmolarity 547 mosmol/L, suggesting an inappropriate AVP secretion. Tolvaptan was introduced at 0.3 mg/kg/day and progressively increased to 3 mg/kg/day on day 4, leading to a partial correction of serum sodium (130 mmol/l) and a urinary osmolarity decrease to 90 mosmol/L. Tolvaptan was then continued at the dose of 3 mg/kg/day with unchanged serum sodium, without hypernatremia or dehydration. Her weight decreased from 14.8 k to 14 k, but oedema still persisted.
Conclusion
Tolvaptan was very efficient in this case of hyponatremia associated with steroid-resistant NS. Tolvaptan should be considered in the management of therapy-resistant hyponatremia in patients with NS.
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References
Pyo HJ, Summer SN, Niederberger M, Kim JK, Schrier RW (1995) Arginine vasopressin gene expression in rats with puromycin-induced nephrotic syndrome. Am J Kidney Dis 25:58–62
Costello-Boerrigter LC, Smith WB, Boerrigter G, Ouyang J, Zimmer CA, Orlandi C, Burnett JC (2006) Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure. Am J Physiol Renal Physiol 290:F273–F278. https://doi.org/10.1152/ajprenal.00195.2005
Decaux G, Soupart A, Vassart G (2008) Non-peptide arginine-vasopressin antagonists: the vaptans. Lancet 371:1624–1632. https://doi.org/10.1016/S0140-6736(08)60695-9
Park E-S, Huh Y, Kim G-H (2015) Is tolvaptan indicated for refractory oedema in nephrotic syndrome? Nephrology (Carlton) 20:103–106. https://doi.org/10.1111/nep.12348
Shimizu M, Ishikawa S, Yachi Y, Muraoka M, Tasaki Y, Iwasaki H, Kuroda M, Ohta K, Yachie A (2014) Tolvaptan therapy for massive edema in a patient with nephrotic syndrome. Pediatr Nephrol 29:915–917. https://doi.org/10.1007/s00467-013-2687-1
Tanaka A, Nakamura T, Sato E, Ueda Y, Node K (2017) Different effects of Tolvaptan in patients with idiopathic membranous nephropathy with Nephrotic syndrome. Intern Med 56:191–196. https://doi.org/10.2169/internalmedicine.56.7539
Hoorn EJ, Lindemans J, Zietse R (2006) Development of severe hyponatraemia in hospitalized patients: treatment-related risk factors and inadequate management. Nephrol Dial Transplant 21:70–76. https://doi.org/10.1093/ndt/gfi082
Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH (2007) Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med 120:S1–S21. https://doi.org/10.1016/j.amjmed.2007.09.001
Usberti M, Federico S, Meccariello S, Cianciaruso B, Balletta M, Pecoraro C, Sacca L, Ungaro B, Pisanti N, Andreucci VE (1984) Role of plasma vasopressin in the impairment of water excretion in nephrotic syndrome. Kidney Int 25:422–429
Apostol E, Ecelbarger CA, Terris J, Bradford AD, Andrews P, Knepper MA (1997) Reduced renal medullary water channel expression in puromycin aminonucleoside--induced nephrotic syndrome. J Am Soc Nephrol 8:15–24
Tuli G, Tessaris D, Einaudi S, Sanctis LD, Matarazzo P (2017) Tolvaptan treatment in children with chronic Hyponatremia due to inappropriate antidiuretic hormone secretion: a report of three cases. J Clin Res Pediatr Endocrinol 9:288–292. https://doi.org/10.4274/jcrpe.4531
Bockenhauer D (2014) Draining the edema: a new role for aquaretics? Pediatr Nephrol 29:767–769. https://doi.org/10.1007/s00467-014-2763-1
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E (2014) Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant 29:i1–i39. https://doi.org/10.1093/ndt/gfu040
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ (2013) Diagnosis, evaluation, and treatment of Hyponatremia: expert panel recommendations. Am J Med 126:S1–S42. https://doi.org/10.1016/j.amjmed.2013.07.006
Doucet A, Favre G, Deschênes G (2007) Molecular mechanism of edema formation in nephrotic syndrome: therapeutic implications. Pediatr Nephrol 22:1983–1990. https://doi.org/10.1007/s00467-007-0521-3
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Delbet, JD., Parmentier, C. & Ulinski, T. Tolvaptan therapy to treat severe hyponatremia in pediatric nephrotic syndrome. Pediatr Nephrol 35, 1347–1350 (2020). https://doi.org/10.1007/s00467-020-04530-6
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DOI: https://doi.org/10.1007/s00467-020-04530-6