Skip to main content

Advertisement

SpringerLink
Log in

The effects of sodium valproate on the renal function of children with epilepsy

  • Review
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Sodium valproate is one of the most commonly used drugs to treat epilepsy. However, there is growing evidence that valproate can cause renal tubular injury in children, and there are increasing reports of valproate-induced Fanconi’s syndrome where the renal tubules lose their ability to reabsorb electrolytes, urea, glucose and protein. In this review article we attempt to bring together all of the studies conducted to date on the effects of valproate on renal function in epileptic children. The research is generally considered in two themes; the first comprises studies which indicate subclinical tubular injury measured by renal enzymes such as N-acetyl-β-D-glucosaminidase (NAG), and the second comprises clinical reports where Fanconi’s syndrome has occurred. This article goes on to analyse the current data and draws on recurring patterns to suggest that a specific subpopulation of severely disabled epileptic children may benefit hugely from the close monitoring of enzymes which are indicative of renal tubular injury, particularly NAG or in the very least periodical urinalysis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Tseng CL, Wang PJ, Tsau YK, Lin MY, Shen YZ (1992) Urinary N-acetyl-beta-glucosaminidase (NAG) in children receiving antiepileptic drugs. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 33:251–256

    CAS  PubMed  Google Scholar 

  2. Novo MLP, Izumi T, Yokota K, Fukuyama Y (1993) Urinary excretion of N-acetyl-β-glucosaminidase and β-galactosidase by patients with epilepsy. Brain Dev 15:157–160

    Article  Google Scholar 

  3. Otsuka T, Sunaga Y, Hikima A (1994) UrinaryN-acetyl-β-glucosaminidase and guanidinoacetic acid levels in epileptic patients treated with anti-epileptic drugs. Brain Dev 16:437–440

    Article  CAS  PubMed  Google Scholar 

  4. Korinthenberg R, Wehrle L, Zimmerhackl LB (1994) Renal tubular dysfunction following treatment with antiepileptic drugs. Eur J Pediatr 153:855–858

    Article  CAS  PubMed  Google Scholar 

  5. Ryan SJ, Bishof NA, Baumann RJ (1996) Occurrence of renal fanconi syndrome in children on valproic acid therapy. J Epilepsy 9:35–38

    Article  Google Scholar 

  6. Yuksel A, Cengiz M, Seven M, Cengiz S, Cenani A (1999) N-acetyl-beta-glucosaminidase and beta-galactosidase activity in children receiving antiepileptic drugs. Pediatr Neurol 20:24–26

    Article  CAS  PubMed  Google Scholar 

  7. Verrotti A, Greco R, Pascarella R, Matera V, Morgese G, Chiarelli F (2000) Renal tubular function in patients receiving anticonvulsant therapy: a long-term study. Epilepsia 41:1432–1435

    Article  CAS  PubMed  Google Scholar 

  8. Korinthenberg R, Säger J, Zimmerhackl LB (2000) Increased urinary excretion of tubular enzymes and proteins in children with epilepsy. Eur J Pediatr Neurol 4:263–267

    Article  CAS  Google Scholar 

  9. Csáthy L, Oláh AV, Clemens B, György I, Varga J (2000) Urinary N-acetyl-β-d-glucosaminidase in epileptic children treated with antiepileptic drugs. Arch Dis Child 83:420–422

    Article  PubMed Central  PubMed  Google Scholar 

  10. Altunbasak S, Yıldız D, Anarat A, Burgut HR (2001) Renal tubular dysfunction in epileptic children on valproic acid therapy. Pediatr Nephrol 16:256–259

    Article  CAS  PubMed  Google Scholar 

  11. Yoshikawa H, Yamazaki S, Watanabe T, Abe T (2003) Hypouricemia in severely disabled children: influence of valproic acid and bed-ridden state. Brain Dev 25:186–190

    Article  PubMed  Google Scholar 

  12. Attilakos A, Voudris KA, Garoufi A, Mastroyianni S, Dimou S, Prassouli A, Katsarou E (2006) Effect of sodium valproate monotherapy on serum uric acid concentrations in ambulatory epileptic children: a prospective long-term study. Eur J Paediatr Neurol 10:237–240

    Article  PubMed  Google Scholar 

  13. Unay B, Akin R, Sarici SU, Gok F, Kurt I, Gokcay E (2006) Evaluation of renal tubular function in children taking anti-epileptic treatment. Nephrology 11:485–488

    Article  CAS  PubMed  Google Scholar 

  14. Mazaheri M, Samaie A, Semnani V (2011) Renal tubular dysfunction measured by N-acetyl-beta glucosaminidase/Creatinine activity index in children receiving antiepileptic drugs: a randomized controlled trial. Ital J Pediatr 37:21

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Lenoir GR, Perignon JL, Gubler MC, Broyer M (1981) Valproic-acid—A possible cause of proximal tubular renal syndrome. J Pediatr 98:503–504

    Article  CAS  PubMed  Google Scholar 

  16. Hawkins E, Brewer E (1993) Renal toxcity induced by valproic acid (Depakene)—case 4. Pediatr Pathol 13:863–868

    Article  CAS  PubMed  Google Scholar 

  17. Lande MB, Kim MS, Bartlett C, Guaywoodford LM (1993) Reversible Fanconi syndrome-associated with valproate therapy. J Pediatr 123:320–322

    Article  CAS  PubMed  Google Scholar 

  18. Smith GC, Balfe JW, Kooh SW (1995) Anticonvulsants as a cause of Fanconi syndrome. Nephrol Dial Transplant 10:543–545

    CAS  PubMed  Google Scholar 

  19. Fukuda Y, Watanabe H, Ohtomo Y, Yabuta K (1996) Immunologically mediated chronic tubulo-interstitial nephritis caused by valproate therapy. Nephron 72:328–329

    Article  CAS  PubMed  Google Scholar 

  20. Zaki EL, Springate JE (2002) Renal injury from valproic acid: case report and literature review. Pediatr Neurol 27:318–319

    Article  PubMed  Google Scholar 

  21. Yoshikawa H, Watanabe T, Abe T (2002) Fanconi syndrome caused by sodium valproate: report of three severely disabled children. Eur J Paediatr Neurol 6:165–167

    Article  PubMed  Google Scholar 

  22. Knorr M, Schaper J, Harjes M, Mayatepek E, Rosenbaum T (2004) Fanconi syndrome caused by antiepileptic therapy with valproic acid. Epilepsia 45:868–871

    Article  PubMed  Google Scholar 

  23. Watanabe T, Nakayasu K, Nagayama Y (2005) Autoimmune haemolytic anaemia and renal Fanconi syndrome caused by valproate therapy. Eur J Pediatr 164:186–187

    Article  PubMed  Google Scholar 

  24. Watanabe T, Yoshikawa H, Yamazaki S, Abe Y, Abe T (2005) Secondary renal Fanconi syndrome caused by valproate therapy. Pediatr Nephrol 20:814–817

    Article  PubMed  Google Scholar 

  25. Endo A, Fujita Y, Fuchigami T, Takahashi S, Mugishima H (2010) Fanconi syndrome caused by valproic acid. Pediatr Neurol 42:287–290

    Article  PubMed  Google Scholar 

  26. Inoue T, Tanaka Y, Otani R, Itabashi H, Murakami N, Nagai T, Sakuta R (2011) Three cases of Fanconi syndrome associated with valproate sodium treatment. No To Hattatsu 43:233–237

    PubMed  Google Scholar 

  27. Shiari R, Bagherzade L, Alaei MR (2011) Fanconi syndrome associated with valporic acid: a case report. Iran Red Crescent Med J 13:844–845

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Dhillon N, Hogler W (2011) Fractures and fanconi syndrome due to prolonged sodium valproate use. Neuropediatrics 42:119–121

    Article  CAS  PubMed  Google Scholar 

  29. Skalova S (2005) The diagnostic role of urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in the detection of renal tubular impairment. Acta Med (Hradec Kralove) 48:75–80

    Google Scholar 

  30. Sönmez F, Dönmez O, Önmez HM, Keskınoğlu A, Kabasakal C, Mır S (2002) Lead exposure and urinary N-acetyl β D glucosaminidase activity in adolescent workers in auto repair workshops. J Adolesc Health 30:213–216

    Article  PubMed  Google Scholar 

  31. Watanabe K, Kojima T, Fukuda Y, Ohbayashi K, Kobayashi T, Iwase S, Kobayashi Y (1987) Reliability of urinary N-acetyl-beta-D-glucosaminidase as an indicator or renal tubular damage in neonates. Biol Neonate 52:16–21

    Article  CAS  PubMed  Google Scholar 

  32. Norden AGW, Gardner SC, van’t Hoff W, Unwin RJ (2008) Lysosomal enzymuria is a feature of hereditary Fanconi syndrome and is related to elevated CI-mannose-6-P-receptor excretion. Nephrol Dial Transplant 23:2795–2803

    Article  CAS  PubMed  Google Scholar 

  33. Maesaka JK, Fishbane S (1998) Regulation of renal urate excretion: a critical review. Am J Kidney Dis 32:917–933

    Article  CAS  PubMed  Google Scholar 

  34. Fichsel G, Fichsel H, Liappis N (1993) Uric-acid serum concentration and antiepileptic treatment in childhood. Klin Padiatr 205:429–431

    Article  CAS  PubMed  Google Scholar 

  35. Mathew G, Knaus SJ (2006) Acquired Fanconi's syndrome associated with tenofovir therapy. J Gen Intern Med 21:C3–C5

    Article  PubMed Central  PubMed  Google Scholar 

  36. Sebastian A, McSherry E, Morris RC Jr (1971) On the mechanism of renal potassium wasting in renal tubular acidosis associated with the Fanconi syndrome (type 2 RTA). J Clin Invest 50:231–243

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Cantani A, Mastrantoni F (1989) Hyperaminoaciduria: Toni-Fanconi and Lowe syndrome. Riv Eur Sci Med Farmacol 11:123–128

    CAS  PubMed  Google Scholar 

  38. Lin CY, Chiang H (1988) Sodium-valproate-induced interstitial nephritis. Nephron 48:43–46

    Article  CAS  PubMed  Google Scholar 

  39. Finsterer J (2004) Mitochondriopathies. Eur J Neurol 11:163–186

    Article  CAS  PubMed  Google Scholar 

  40. Yoshikawa H, Yamazaki S, Abe T (2004) Hypouricemia in severely disabled children II: influence of elemental enteral nutrition on the serum uric acid levels. Brain Dev 26:43–46

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Leeds School of Medicine, University of Leeds, Worsley Building, Room 7.9, Leeds, UK, LS2 9JT

    Mark Jonathan Knights

  2. Paediatric and Nephrology Department, Leeds University Teaching Hospitals, Leeds, UK

    Eric Finlay

Authors
  1. Mark Jonathan Knights
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eric Finlay
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark Jonathan Knights.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Knights, M.J., Finlay, E. The effects of sodium valproate on the renal function of children with epilepsy. Pediatr Nephrol 29, 1131–1138 (2014). https://doi.org/10.1007/s00467-013-2512-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-013-2512-x

Keywords

Search

Navigation