肾小管功能在亚临床糖尿病肾病诊断价值中的初步探讨

Diagnostic value of renal tubular function in subclinical diabetic nephropathy

目的 观察2型糖尿病患者的肾小管功能,分析肾小管损伤标记物与亚临床糖尿病肾病（DN）的关系.方法 298例2型糖尿病患者根据24h尿微量白蛋白（UMA）和估算的肾小球滤过率（GFR）分为对照组（NC组,正常白蛋白尿及正常滤过率,n=100）、亚临床DN组（SDN组,正常白蛋白尿高滤过率,n =87）和早期DN组（EDN组,微量白蛋白尿,n=111）.应用免疫透射比浊法检测24 h UMA、尿视黄醇结合蛋白（RBP）、尿β2-微球蛋白（β2-MG）,生化法测定尿N-乙酰-D-氨基葡萄糖苷酶（NAG）、β-半乳糖苷酶（GAL）,分析各组肾小管损伤标记物及其与亚临床DN的关系.结果 与NC组相比,SDN组NAG较高（χ2=9.032,P＜O.01）,而与EDN组差异无统计学意义;EDN组RBP水平明显高于NC组及SDN组（χ2=56.341,31.955,P均＜0.01）;NC组、SDN组、EDN组GAL、β2-MG水平呈升高趋势,但差异无统计学意义.与NC组相比,SDN组及EDN组近端肾小管功能异常率较高（分别为59％,82％,78.2％,χ2=42.658,P＜0.01）.SDN组肾小管损伤标记物中一项或两项异常者的比例高于NC组及EDN组.肾小管损伤标记物中两项异常者有发生亚临床DN的风险[优势比（OR）=2.9,P=0.005],但经校正年龄、性别、糖尿病病程、总甘油三酯、总胆固醇、高密度脂蛋白-胆固醇、糖化血红蛋白、体重指数后,差异无统计学意义（OR=1.7,P＞0.05）.结论 肾小管损伤可能对早期肾功能减退的判断较肾小球损伤更重要,尿白蛋白正常但GFR升高的亚临床DN患者肾小管损伤标记物的水平升高及种类增多.

Objective To investigate the renal tubular function in type 2 diabetic patients,and analyze the relationship between tubular injury markers and subclinical diabetic nephropathy （DN）.Methods Two hundred and ninty-eight patients with type 2 diabetes were divided into three groups based on their 24-hour urinary microalbumin （UMA） and estimated glomerular filtration rate （eGFR）：normal control group （NC group,with normal albuminuria and eGFR,n =100）,subclinical diabetic nephropathy group （SDN group,with normoalbuminuria and glomerular hyperfiltration,n =87） and early diabetic nephropathy group （EDN group,with microalbuminuria,n =111）.Immunoturbidimetric method was used to detect the level of 24-hour UMA,retinol binding protein （RBP） and β2-microglobubin（β2-MG） in urine.Biochemical method was used to measure N-acetyl-β-D-glucosaminidase （NAG） and galactosidase （GAL） in urine.The tubular injury markers and the relationship between renal tubular function and subclinical DN were analyzed.Results NAG in SDN group was higher than that in NC group （χ2 =9.032,P 〈 0.01）,but no difference was found between SDN and EDN group.Urinary RBP in EDN group was greater than those in other two groups （χ2 =56.341,31.955,all P 〈0.01）.Although there was an increasing trend,the levels of β2-MG and GAL in NC,SDN and EDN group had no statistical difference.Compared with NC group,the percentages of patients with proximal tubular dysfunction were higher,in SDN and EDN group （59%,78.2%,82% respectively,χ2 =42.658,P 〈 0.01）.The percentage of patients with one or two tubular injury markers in SDN group was greater than those in other two groups.Patients with two tubular injury markers were more likely to suffer from subclinical DN [odd ratio （OR） =2.9,P =0.005],but after adjusting for age,sex,diabetic duration,total triglyceride,total cholesterol,high density lipoprotein-cholesterol,glycosylated hemoglobin and body mass index,the predictive value disappeared （OR =1.7,P 〉 0.05）.Conclusion Compared with glomerular injury,tubular injury may be more important for judging the early impairment in renal function.Subclinical DN patients with normoalbuminuria and hyperfiltration have higher level of tubular injury markers.