Renal tubular dysfunction following treatment with anti-epileptic drugs

Abstract

To evaluate renal side-effects of anti-epileptic medication in children, we performed a cross-sectional study of various aspects of renal function. We studied 59 patients from our outpatient clinic. They had been on anti-epileptic monotherapy for at least 3 months. None had a history of renal disease. Twenty-three healthy children of the same age group served as controls. After collecting 24-h urine samples, glomerular function was derived from creatinine clearance and from the excretion of albumin. Proximal tubular function was investigated by the urinary excretion of alpha 1-microglobulin and of the tubular enzymes N-acetyl-beta-D-glucosaminidase, alanine-amino-peptidase and fructose-1,6-di-phosphatase. Distal tubular function was examined by the 24-h excretion of Tamm-Horsfall protein. On treatment with carbamazepine (n = 27) and phenytoin (n = 8), the excretion of alpha 1-microglobulin was significantly increased, as compared with the healthy controls. On valproate (n = 20), ethosuximide (n = 9) and phenytoin (n = 8), therapies significantly increased excretion of N-acetyl-beta-D-glucosaminidase. This must be interpreted as an indication of a functional disturbance of the proximal tubulus. The other parameters, indicating function of the glomerulus, loop of Henle and distal tubules did not differ from normal. Patients on anti-epileptic treatment with therapeutic drug levels may demonstrate minor signs of tubular dysfunction. These are probably insignificant from a clinical standpoint, but they should be considered in drug overdose.