# The effects of valproic acid and levetiracetam treatments on kidney functions in children with epilepsy

## TL;DR

This study found that valproic acid may cause increased kidney filtration in children with epilepsy, but no signs of kidney damage were seen with either valproic acid or levetiracetam.

## Contribution

The study introduces novel biomarkers to assess kidney function in children on anti-epileptic drugs.

## Key findings

- Valproic acid was associated with glomerular hyperfiltration in children with epilepsy.
- No significant differences in tubular function markers were found between valproic acid, levetiracetam, and control groups.
- Levetiracetam showed no significant impact on kidney function compared to healthy controls.

## Abstract

Clinical and subclinical evidence of kidney dysfunction has been reported with the use of some anti-epileptic drugs (AEDs) in children. This study aimed to evaluate renal tubular and glomerular functions using novel biomarkers N-acetyl-β-d-glycosaminidase (NAG), Kidney Injury Molecule-1(KIM-1) and 24-hour measured creatinine clearance (mClcr) in patients taking valproic acid (VPA) and levetiracetam (LEV).

Fifty-one epileptic patients were included in this prospective case-control study between January 2023 and January 2024 in The Ankara Training and Research Hospital. Exclusions were made for individuals on multiple AEDs, those with incomplete data, bedridden patients, concurrent conditions (hypertension, obesity), or those using steroids or other medications. Participants had been on either VPA or LEV for at least six months. Sixteen healthy age- and sex-matched children served as the control group. Blood samples and 24-hour urine NAG, KIM-1, and mClcr measurements were collected.

The VPA, LEV, and control group comprised 30, 21, and 16 patients, respectively. The VPA group had higher urinary pH (6.1±0.7) and mClcr levels (173.4±48.0) than LEV (5.6±0.5, 149.7±39.1) and control (5.6±0.6, 130.6±30.6) groups. No significant difference was observed in urinary pH and mClcr levels between the LEV and control groups (p>0.05). No statistically significant differences were observed among the VPA, LEV, and control groups regarding 24-hour urinary NAG, KIM-1, NAG/creatinine, and KIM-1/creatinine levels (p>0.05). There was no significant association between mClcr levels and duration of treatment or serum drug levels on Spearman’s correlation coefficient (p>0.05).

We found VPA-associated glomerular hyperfiltration in children with epilepsy. We did not observe tubular dysfunction in patients on VPA or LEV.