肝豆状核变性患者的肾脏病变特点及长期使用青霉胺的影响研究

Effect of long-term administration of D-penicillamine on kidney function in patients with hepatolenticular degeneration

目的 探讨肝豆状核变性患者肾脏病变的特点及长期使用青霉胺治疗对其产生的可能影响.方法 选取70例临床确诊为肝豆状核变性患者作为观察组,根据临床表型和使用青霉胺时间分为肝脏型组、肝脑混合型组、脑型组及使用青霉胺＜5年组、5～10年组、＞10年组,检测并比较各组患者尿总蛋白（TG）、低分子量蛋白（LMW）、高分子量蛋白（HMW）、β2微球蛋白（β2-MG）、β-N-乙酰氨基葡萄糖苷酶（NAG）、白蛋白（ALG）及血肌酐（Scr）等肾脏病变相关指标;另选择无血缘关系且血铜蓝蛋白及铜氧化酶等铜代谢检查均正常的健康志愿者70例作为对照组,检测上述指标并与观察组对照.结果 观察组的肾脏病变相关指标显著高于对照组;不同临床表型的患者各项指标间无统计学差异;随着服用青霉胺时间的延长,患者尿液中β2-MG、LMW百分比、NAG、TG水平逐渐降低,HMW百分比、ALG水平逐渐升高,TG呈现逐渐降低的趋势,Scr保持不变.结论 肝豆状核变性患者肾小球和肾小管的功能均有明显的损伤;肾脏病变在不同临床表型之间无统计学差异,长期使用青霉胺治疗对肾小球的功能有一定的损伤.

Objective To investigate the effect of long-term administration of D-penicillamine on renal function in pa- tients with hepatolenticular degeneration. Methods Seventy patients with hepatolenticular degenerationas （observation group） and 70 healthy subjects （control group） were enrolled in the study. Patients received penicillamine therapy for 〈5y, 5-10y and 〉 10y, respectively. The urinary total protein （TG）, low molecular weight protein （LMW）, high molecular weight protein （HMW）, 132-microglobulin （β2-MG）, β-D-N-acetyl-d-glucosaminidase （NAG）, albumin （ALG） and serum creatinine （Scr） were de- tected and compared between overservation group and control group, and among different groups of patients. Results Kidney disease related indicators in observation group was significantly higher than those in control group; no significant difference the renal function indexes was found among different clinical phenotypes. With the prolonging of penicillamine administration the uri- nary β2-MG, LMW, NAG, TG levels were decreased gradually, and the ALG and HMW were gradually increased, the Scr levels were unchanged. Conclusion Patients with hepatolenticular degeneration have significant renal glomerular and tubular injury; and long-term administration of penicillamine therapy may damage renal glomerular function.