[P2-126] Study of risk factors for Valproate-induced Fanconi Syndrome
Background and aims: There have been increasing reports of drug-induced Fanconi syndrome (FS) caused by sodium valproate (VPA). The onset mechanism is unclear. However, it has been recently reported that VPA can cause hypocarnitinemia, suggesting its involvement in dysfunction of the proximal renal tubules. In order to achieve early diagnosis, this study was conducted to elucidate the risk factors for development of VPA-induced FS.
Subjects and Methods: The subjects were 86 patients (4–48 years, 52 males) who were diagnosed with epilepsy and administered VPA. Patients with urine BMG/Cr levels above 210µg/gCr were treated as FS group (n=17), with all others treated as non-FS group (n=69), and the patient backgrounds and laboratory findings were compared between them.
Results: There was no difference in age, gender, duration of administration, blood VPA concentration or serum Cystatin-C levels. However, there were more patients who are bedridden, having enteral nutrition and much anticonvulsant in the FS group. Also, in examination values, we found depressed serum uric acid levels (FS vs. non-FS median value: 2.3 vs. 5.1mg/dl, p<0.0001), serum phosphorus levels (3.5 vs. 4.0mg/dl, p=0.028), serum creatinine levels (0.34 vs. 0.51mg/dl, p=0.00018) and serum free carnitine levels (29 vs. 44.6µmol/L, p=0.0012). A multivariate analysis found that free carnitine levels were significantly lower, and bedridden patients were significantly higher in the FS group.
Conclusions: In bedridden patients with reduced serum free carnitine concentration, the risk of developing to VPA-induced FS is significantly high. Therefore, blood free carnitine levels and urinary BMG/Cr levels should be monitored.
Subjects and Methods: The subjects were 86 patients (4–48 years, 52 males) who were diagnosed with epilepsy and administered VPA. Patients with urine BMG/Cr levels above 210µg/gCr were treated as FS group (n=17), with all others treated as non-FS group (n=69), and the patient backgrounds and laboratory findings were compared between them.
Results: There was no difference in age, gender, duration of administration, blood VPA concentration or serum Cystatin-C levels. However, there were more patients who are bedridden, having enteral nutrition and much anticonvulsant in the FS group. Also, in examination values, we found depressed serum uric acid levels (FS vs. non-FS median value: 2.3 vs. 5.1mg/dl, p<0.0001), serum phosphorus levels (3.5 vs. 4.0mg/dl, p=0.028), serum creatinine levels (0.34 vs. 0.51mg/dl, p=0.00018) and serum free carnitine levels (29 vs. 44.6µmol/L, p=0.0012). A multivariate analysis found that free carnitine levels were significantly lower, and bedridden patients were significantly higher in the FS group.
Conclusions: In bedridden patients with reduced serum free carnitine concentration, the risk of developing to VPA-induced FS is significantly high. Therefore, blood free carnitine levels and urinary BMG/Cr levels should be monitored.