Abstract
AIM—To investigate the effect of prolonged use of antiepileptic drugs on renal function in children. METHODS—Prospective study of 72 children (aged 3-18 years) with epilepsy, on either monotherapy (n = 44) or combined therapy (n = 28). The length of treatment varied from 1 to 13 years. Drugs used were valproic acid, carbamazepine, ethosuximide, clonazepam, clobazepam, and vigabatrin. RESULTS—In 65 patients plasma concentrations of the drugs were in the therapeutic range. In the remaining seven, plasma concentrations were slightly high. In 33 patients urinary N-acetyl-β-D-glucosaminidase (NAG) activity was raised. The incidence of pathological NAG indices was significantly higher in the combined therapy group than in the monotherapy group. There were also significant differences in the NAG indices of patients depending on the duration of therapy. CONCLUSIONS—Results suggest that chronic use of some antiepileptic drugs—in spite of normal blood concentrations—may alter tubular function, and the dysfunction may result in clinical symptoms. Therefore, we recommend screening of tubular function in these patients.
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- Csáthy L., Pócsi I. Urinary N-acetyl-beta-D-glucosaminidase determination in newborns and children: methods and diagnostic applications. Eur J Clin Chem Clin Biochem. 1995 Sep;33(9):575–587. [PubMed] [Google Scholar]
- Hogg R. J., Sawyer M., Hecox K., Eigenbrodt E. Carbamazepine-induced acute tubulointerstitial nephritis. J Pediatr. 1981 May;98(5):830–832. doi: 10.1016/s0022-3476(81)80861-x. [DOI] [PubMed] [Google Scholar]
- Kunin C. M., Chesney R. W., Craig W. A., England A. C., DeAngelis C. Enzymuria as a marker of renal injury and disease: studies of N-acetyl-beta-glucosaminidase in the general population and in patients with renal disease. Pediatrics. 1978 Nov;62(5):751–760. [PubMed] [Google Scholar]
- Lenoir G. R., Perignon J. L., Gubler M. C., Broyer M. Valproic acid: a possible cause of proximal tubular renal syndrome. J Pediatr. 1981 Mar;98(3):503–504. doi: 10.1016/s0022-3476(81)80736-6. [DOI] [PubMed] [Google Scholar]
- Lin C. Y., Chiang H. Sodium-valproate-induced interstitial nephritis. Nephron. 1988;48(1):43–46. doi: 10.1159/000184867. [DOI] [PubMed] [Google Scholar]
- Novo M. de L., Izumi T., Yokota K., Fukuyama Y. Urinary excretion of N-acetyl-beta-glucosaminidase and beta-galactosidase by patients with epilepsy. Brain Dev. 1993 Mar-Apr;15(2):157–160. doi: 10.1016/0387-7604(93)90055-d. [DOI] [PubMed] [Google Scholar]
- Otsuka T., Sunaga Y., Hikima A. Urinary N-acetyl-beta-glucosaminidase and guanidinoacetic acid levels in epileptic patients treated with anti-epileptic drugs. Brain Dev. 1994 Nov-Dec;16(6):437–440. doi: 10.1016/0387-7604(94)90003-5. [DOI] [PubMed] [Google Scholar]
- Price R. G. Urinary enzymes, nephrotoxicity and renal disease. Toxicology. 1982;23(2-3):99–134. doi: 10.1016/0300-483x(82)90092-0. [DOI] [PubMed] [Google Scholar]
- Pócsi I., Csáthy L., Oláh V. A., Price R. G. Assay of N-acetyl-beta-D-glucosaminidase in urine from neonates: comparison of two new colorimetric methods using MNP-GlcNAc and VRA-GlcNAc as substrates. Ann Clin Biochem. 1992 May;29(Pt 3):292–295. doi: 10.1177/000456329202900307. [DOI] [PubMed] [Google Scholar]
- Ray-Chaudhuri K., Pye I. F., Boggild M. Hypersensitivity to carbamazepine presenting with a leukemoid reaction, eosinophilia, erythroderma, and renal failure. Neurology. 1989 Mar;39(3):436–438. doi: 10.1212/wnl.39.3.436. [DOI] [PubMed] [Google Scholar]
- Silverman S. H., Gribetz D., Rausen A. R. Nephrotic syndrome associated with ethosuccimide. Am J Dis Child. 1978 Jan;132(1):99–99. doi: 10.1001/archpedi.1978.02120260101027. [DOI] [PubMed] [Google Scholar]
- Tseng C. L., Wang P. J., Tsau Y. K., Lin M. Y., Shen Y. Z. Urinary N-acetyl-beta-glucosaminidase (NAG) in children receiving antiepileptic drugs. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1992 Jul-Aug;33(4):251–256. [PubMed] [Google Scholar]
- Watanabe K., Kojima T., Fukuda Y., Ohbayashi K., Kobayashi T., Iwase S., Kobayashi Y. Reliability of urinary N-acetyl-beta-D-glucosaminidase as an indicator of renal tubular damage in neonates. Biol Neonate. 1987;52(1):16–21. doi: 10.1159/000242679. [DOI] [PubMed] [Google Scholar]
- Yüksel A., Cengiz M., Seven M., Cengiz S., Cenani A. N-acetyl-beta-glucosaminidase and beta-galactosidase activity in children receiving antiepileptic drugs. Pediatr Neurol. 1999 Jan;20(1):24–26. doi: 10.1016/s0887-8994(98)00079-4. [DOI] [PubMed] [Google Scholar]