Does Nephrotoxicity Exist in Pediatric Epileptic Patients on Valproate or Carbamazepine Therapy?

Abstract

The aim of this study was to investigate the effects of valproate and carbamazepine, on renal glomerular and tubular functions. The patient group comprised 54 children with new-onset epilepsy treated with valproate (n = 30) and carbamazepine (n = 24). Twenty-six healthy children were in the control group. The serum creatinine and cystatin C levels and urinary excretion of N-acetyl-β-d-glucosaminidase (NAG) levels were measured and the glomerular filtration rate (GFR) was estimated. Serum creatinine and cystatin C concentrations were not different between patients and controls. The glomerular filtration rate of the patient groups were higher than those of the control group. Thus, both drugs probably lead to glomerular hyperfiltration and toxicity for glomerular functions. However, urinary N-acetyl-β-d-glucosaminidase/creatinine levels were significantly higher in patients receiving only valproate (6.1 ± 5). The difference between carbamazepine and control groups was not significant for urinary N-acetyl-β-d-glucosaminidase/creatinine levels. Our data suggest that valproate has adverse effects on renal tubular functions.

Comparison of the Effects of Sodium Valproate and Carbamazepine on Renal Function in Children With Epilepsy

“…The findings of these studies and those of ours demonstrate a higher renal tubular damage with VPA. Nevertheless, it should be noted that the duration of treatment, drug blood levels, and the baseline status of tubular function might have been different in these studies, leading to significant findings in our study and nonsignificant results in the studies of Mazaheri et al and Havali et al (12,14). Contrary to our results, Endo et al found a significantly higher α 1 -microglobulin (another indicator of renal tubular dysfunction) excretion with CBZ monotherapy rather than VPA monotherapy (18).…”

“…Similar to our results, Mazaheri et al reported a higher NAG/creatinine index with VPA in comparison to CBZ, yet without a statistically significant difference (12). Havali et al also concluded that urine NAG levels were significantly higher in the VPA group compared to controls, while the difference between the CBZ group and controls was not statistically significant (14). The findings of these studies and those of ours demonstrate a higher renal tubular damage with VPA.…”

“…Not many studies have compared the effects of these drugs on serum creatinine levels. Nonetheless, serum creatinine levels were almost similar in the CBZ and VPA groups of the study by Havali et al, with nonsignificant differences between both groups and controls (14). Although we found significantly higher serum creatinine levels in the VPA group, the mean creatinine was still within normal limits in both groups.…”

Kidney tubular injury induced by valproic acid: systematic literature review

“…For the overt kidney tubular injury study, we retained 28 articles [4, documenting individuals presenting with three or more laboratory features consistent with a kidney tubular injury. We also found 8 reports [40][41][42][43][44][45][46][47] addressing the possible existence of a pauci-symptomatic kidney tubular damage. The mentioned 36 reports [4, were published between 1981 and 2022 in English from the following countries: Japan (N = 11), USA (N = 8), Türkiye (N = 4), UK (N = 3), Canada (N = 2), Germany (N = 2), Italy (N = 2), France (N = 1), Iran (N = 1), Spain (N = 1), and Sri Lanka (N = 1).…”

“…Eight reports [40][41][42][43][44][45][46][47] investigated the possible existence of a pauci-symptomatic kidney tubular injury in 285 epileptic children on valproic acid. The mentioned reports provided information on 5 cross-sectional [43][44][45][46][47] and 4 longitudinal [40][41][42]46] studies.…”