Koga Satoko, Kimata Takahisa, Yamanouchi Sohsaku, Tsuji Shoji, Yoshimura Ken, Araki Atsushi, Kaneko Kazunari
Department of Pediatrics, Kansai Medical University, 2-5-1 Shin-machi, Hirakata-shi, Osaka, 573 1010, Japan.
Clin Exp Nephrol. 2018 Apr;22(2):420-425. doi: 10.1007/s10157-017-1472-z. Epub 2017 Aug 23.
To explore the risk factors for the development of sodium valproate (VPA)-induced renal tubular dysfunction for early diagnosis and treatment.
The subjects were selected from patients who were diagnosed with epilepsy and administered VPA. Blood and spot urine samples were collected and measured the concentration of VPA, the level of serum phosphorus, serum uric acid, serum free carnitine, serum cystatin-c, and urine β2-microglobulin (BMG). Patients with urine BMG/creatinine levels above 219.2 were treated as renal proximal tubular dysfunction (RTD), with all others treated as non-RTD.
Eighty-seven patients, 4-48 years, 53 men and 34 women, were studied. RTD group is 17 patients and non-RTD group is 70 patients. Univariate analyses revealed that the RTD patients were more likely to be bedridden, receiving enteral tube feeding, taking more anticonvulsants, and demonstrating significantly lower serum levels of free carnitine, uric acid, and phosphorus. Among them, bedridden, free serum carnitine, and phosphorus levels were associated with the development of RTD by multivariate analysis.
Bedridden patients receiving VPA are susceptible to hypocarnitinemia, which can cause RTD and may lead to FS. Therefore, urinary BMG should be measured regularly in all patients receiving VPA to assess renal tubular function. An additional measurement of serum free carnitine level should be considered in patients who developed RTD. Supplementation of carnitine for those patients to prevent such complication deserves for further study.
探讨丙戊酸钠（VPA）所致肾小管功能障碍发生的危险因素，以便早期诊断和治疗。
研究对象选自确诊为癫痫并接受VPA治疗的患者。采集血液和随机尿样本，检测VPA浓度、血清磷水平、血清尿酸、血清游离肉碱、血清胱抑素-c和尿β2-微球蛋白（BMG）。尿BMG/肌酐水平高于219.2的患者被视为近端肾小管功能障碍（RTD），其他患者则视为非RTD。
共研究了87例患者，年龄4 - 48岁，男性53例，女性34例。RTD组17例患者，非RTD组70例患者。单因素分析显示，RTD患者更易卧床、接受肠内管饲、服用更多抗惊厥药物，且血清游离肉碱、尿酸和磷水平显著降低。其中，卧床、血清游离肉碱和磷水平经多因素分析与RTD的发生相关。
接受VPA治疗的卧床患者易发生低肉碱血症，可导致RTD并可能引发FS。因此，应定期检测所有接受VPA治疗患者的尿BMG以评估肾小管功能。对于发生RTD的患者，应考虑额外检测血清游离肉碱水平。对这些患者补充肉碱以预防此类并发症值得进一步研究。
