AHMET TANER ELMAS, Serdal GÜNGÖR, Müjgan ARSLAN, Yılmaz TABEL, Sabiha Gungor RAİF, Fatma ÖZYALIN

Evaluation of renal tubular function in epileptic children treated with levetiracetam

Our study aim was to measure the urinary N-acetyl-β-D-glucosaminidase/creatinine (NAG/UCr) index in epileptic children who received levetiracetam (LEV) treatment at least for 6 months, and compare it to healthy children. Thirty five children with epilepsy were enrolled in this prospective study. NAG was studied using the calorimetric method and NAG levels were expressed in units per liter (U/L) and NAG/UCre levels were determined in U/mmol creatinine. There were no statistically significant differences for the urine NAG and NAG/UCr index before and after LEV treatment in the epileptic group (p>0.05, for each). There were no significant correlations between the serum concentration of LEV and urinary NAG levels (r=0.258, p=0.135) and NAG/UCr levels (r=0.164, p=0.346) before treatment. Our study demonstrated that LEV treatment was safe and did not interfere in renal tubular function in epileptic children

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1. Csáthy L, Pócsi I. Urinary N-acetyl-â-D-glucosaminidase determination in newborns and children: methods and diagnostic applications. Eur J Clin Chem Clin Biochem. 1995;33(9):575–87.

2. Price RG. Urinary enzymes, nephrotoxicity and renal disease. Toxicology. 1982;23(2-3):98-134.

3. Kunin CM, Chesney RW, Craig WA, England AC, De Angelis C. Enzymuria as a marker of renal injury and disease: studies of Nacetyl-â-D-glucosaminidase in the general population and in patients with renal disease. Pediatrics. 1978;64(5):751-60.

4. Watanabe K, Kojima K, Fukuda J, Ohbayasi K, Kobayashi T, Iwase S. Reliability of urinary N-acetyl-â-D- glucosaminidase as an indicator of renal tubular damage in neonates. Biol Neonate. 1987;52(1):16-21.

5. Perucca E, Meador KJ. Adverse effects of antiepileptic drugs. Acta Neurol Scand Suppl. 2005;181:30-5.

6. Snead OCI. Surgical treatment of medically refractory epilepsy in childhood. Brain Dev. 2001;23(4):199-207.

7. Lynch BA, Lambeng N, Nocka K, Kensel-Hammes P, Bajjalieh SM, Matagne A et al. The synaptic vesicle protein SV2A is the binding site fort he antiepileptic drug levetirecetam. Proc Natl Acad Sci USA. 2004;101(26):9861-6.

8. Lenoir GR, Perignon JL, Gubler MC, Broyer M. Valproic acid: a possible cause of proximal tubular renal syndrome. J Pediatr. 1981;98(3):503-4.

9. Lin CY, Chiang H. Sodium valproate induced interstitial nephritis. Nephron. 1988;48(1):43-6.

10. Hogg RJ, Sawyer M, Hecox K, Eigenbrodt E. Carbamazepine induces acute tubulointerstitial nephritis. J Pediatr. 1981;98(5):830–2. 11. Hurwitz KA, Ingulli EG, Krous HF. Levetiracetam induced interstitial nephritis and renal failure. Pediatr Neurol. 2009;41(1):57- 8.

12. Mahta A, Kim RY, Kesari S. Levetiracetam-induced interstitial nephritis in a patient with glioma. J Clin Neurosci. 2012;19(1):177-8.

13. Novo MLP, Izumi T, Yokota K, Fukuyama Y. Urinary excretion of N-acetyl-â-D-glucosaminidase by patients with epilepsy. Brain Dev. 1993;15(2):157-60.

14. Otsuka T, Sunaga Y, Hikima A. Urinary N-acetyl-â-Dglucosaminidase and guanidinoacetic acid levels in epileptic patients treated with anti-epileptic drugs. Brain Dev. 1994;16(6):437-40.

15. Tseng CL, Wang PJ, Tsau YK, Lin MY, Shen YZ. Urinary of Nacetyl-â-glucosaminidase (NAG) in children receiving antiepileptic drugs. Acta Paediatr Sin. 1992;33(4):251-6.

16. Yüksel A, Cengiz M, Seven M, Cengiz S, Cenani A. N-acetyl-â- glucosaminidase and â-galactosidase in children receiving antiepileptic drugs. Paediatr Neurol. 1999;20(1):24-6.

17. Altınbaşak Ş, Yıldıza D, Anarat A, Burgut HR. Renal tubular dysfunction in epileptic children on valproic acid therapy. Pediatr Nephrol. 2001;16(3):256-9.

18. Patsalos PN. Pharmacokinetic profile of levetiracetam: toward ideal characteristics. Pharmacol Ther. 2000;85(2):77-85.

19. Khurana DS, Kothare SV, Valencia I, Melvin JJ, Legido A. Levetiracetam monotherapy in children with epilepsy. Pediatr Neurol. 2007;36(4):227-30.

20. Bello-Espinosa LE, Roberts SL. Levetiracetam for benign epilepsy of childhood with centrotemporal spikes: 3 cases. Seizure. 2003;12(3):157-9.

21. Patsolas PN. Clinical pharmacokinetics of levetiracetam. Clin Pharmacokinet. 2004;43(11):707-24.

22. Hovinga CA. Levetiracetam: a novel antiepileptic drug. Pharmacotherapy. 2001;21(11):1375-88.

23. Arroyo S, Crawford P. Safety profile of levetiracetam. Epileptic Disord. 2003;5(suppl. 1):S57-63.

24. Choudhury D, Ahmed Z. Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol. 2006;2(2):80-91.

25. De Smedt T, Raedt R, Vonck K, Boon P. Levetiracetam: Part II, the clinical profile of a novel anticonvulsant drug. CNS Drug Rev. 2007;13(1):57-78.

26. Glauser TA, Ayala R, Elterman RD, Mitchell WG, Van Orman CB, Gauer LJ, Lu Z; N159 Study Group. Double-blind placebocontrolled trial of adjunctive levetiracetam in pediatric partial seizures. Neurology. 2006;66(11):1654-60.

27. Cruz DN, Perazella MA. Drug-induced acute tubulointerstitial nephritis: the clinical spectrum. Hosp Pract (Minneap). 1998;33(2):151-2.

28. Pastor-Milan E, Rubert-Gomez MA, Vazguez-Gutierrez F, Gonzalez V. Oxcarbazepine induced interstitial nephritis in a patient with drug hypersensitivity syndrome [In Spanish]. Rev Neurol. 2003;37(10):948-50.

29. Gogtay NJ, Bavdekar SB, Kshirsagar NA. Anticonvulsant hypersensitivity syndrome: a review. Expert Opin Drug Saf. 2005;4(3):571-81.

30. Hurkacz M, Wiela-Hojeńska A, Orzechowska-Juzwenko K, Kozik A, Unolt J. Monitoring of renal function in epileptic children and teenagers treated with valproic acid or carbamazepine in concomitant therapy with tiagabine. Pol Merkur Lekarski. 2001;11(66):480-3.

31. Korinthenberg R, Wehrle L, Zimmerhackl LB. Renal tubular dysfunction following treatment with anti-epileptic drugs. Eur J Pediatr. 1994;153(11):855-8.

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