Wiland Piotr, Szechciński Jacek
Department of Internal Diseases and Rheumatology, Railway Hospital, Wiśniowa 36, PL 53-137 Wrocław, Poland.
Pol J Pharmacol. 2003 Jul-Aug;55(4):631-7.
The present study aimed to determine the relationships between time of administration and dose of aminoglycosides, the extent of proximal tubule damage, evaluated by the urine N-acetyl-beta-D-glucosaminidase (NAG) activity, and to compare proximal tubule dysfunction in the patients treated with gentamicin and those receiving amikacin. The measurement of activity of NAG in urine was chosen to monitor of proximal tubule function. The studies were performed in 25 patients, who had to be administered gentamicin or amikacin by intramuscular injections. In both groups, the maximum NAG activities in urine were detected most frequently after the 7th day of the therapy. A significant difference in NAG activities in urine was noted between the values observed in the course of treatment with aminoglycosides and those determined before start of the treatment. NAG activity in urine significantly decreased following discontinuation of aminoglycoside antibiotic administration. The activities did not decrease quite to the pretreatment level but the remaining difference proved to be insignificant. In the course of aminoglycoside treatment, 7 patients demonstrated an increase in serum creatinine levels exceeding 0.4 mg%. It should be stressed that no pronounced differences in nephrotoxicity and, in particular, in their potential to induce injury to the proximal tubule have been disclosed between gentamicin and amikacin. Their significant, damaging effect on integrity of proximal tubule was demonstrated, which was evidenced by the clear increase in urinary NAG activity during administration of either drug. Nevertheless, only in a small fraction of such cases (12-16%), the increase promoted development of renal insufficiency, usually of a transient character. Monitoring of the increase in urinary NAG activities in line with observations on creatinine levels permits to distinguish a subgroup of patients who may be suspected of development of overt nephrotoxicity. In such cases cessation of aminoglycoside administration is required.
本研究旨在确定氨基糖苷类药物的给药时间和剂量与近端肾小管损伤程度(通过尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性评估)之间的关系,并比较接受庆大霉素治疗的患者和接受阿米卡星治疗的患者的近端肾小管功能障碍。选择测量尿中NAG活性来监测近端肾小管功能。对25例必须通过肌肉注射给予庆大霉素或阿米卡星的患者进行了研究。在两组中,治疗第7天后最常检测到尿中NAG活性的最大值。在氨基糖苷类药物治疗过程中观察到的尿中NAG活性值与治疗开始前测定的值之间存在显著差异。停用氨基糖苷类抗生素后,尿中NAG活性显著下降。活性并未降至治疗前水平,但剩余差异被证明不显著。在氨基糖苷类药物治疗过程中,7例患者的血清肌酐水平升高超过0.4mg%。应该强调的是,庆大霉素和阿米卡星在肾毒性方面,特别是在诱导近端肾小管损伤的潜力方面,没有发现明显差异。它们对近端肾小管完整性有显著的破坏作用,这在两种药物给药期间尿中NAG活性明显增加中得到了证明。然而,只有一小部分此类病例(12%-16%)中,这种增加促进了肾功能不全的发展,通常是短暂性的。根据肌酐水平的观察结果监测尿中NAG活性的增加,可以区分出可能怀疑发生明显肾毒性的患者亚组。在这种情况下,需要停止使用氨基糖苷类药物。