Polkinghorne Kevan R, Su Quing, Chadban Steven J, Shaw Jonathan E, Zimmet Paul Z, Atkins Robert C
Department of Nephrology, Monash Medical Centre, Victoria, Australia.
Am J Kidney Dis. 2006 Apr;47(4):604-13. doi: 10.1053/j.ajkd.2005.12.034.
Microalbuminuria is an independent risk factor for cardiovascular morbidity and mortality in the general population. Standard immunochemical urinary albumin assays detect immunoreactive albumin, whereas high-performance liquid chromatography (HPLC) detects both immunoreactive and immunounreactive albumin.
Using data from the Australian Diabetes, Obesity, and Lifestyle cohort study of randomly selected community-based Australian adults, spot urine samples were tested for albuminuria (spot urine albumin-creatinine ratio [ACR]: normal, < 30 mg/g; microalbuminuria, 30 to 300 mg/g; and macroalbuminuria, > 300 mg/g) by using both immunonephelometry (IN) and HPLC (n = 10,010).
Bland-Altman analysis showed significant bias, with a greater ACR by means of HPLC, particularly at lower levels of ACR. Mean ACR was 15.8 mg/g (95% confidence interval [CI], 12.3 to 19.2) by means of IN compared with 30.0 mg/g (95% CI, 27.0 to 35.0) by means of HPLC. The prevalence of microalbuminuria was 4 times greater by means of HPLC compared with IN (20% versus 5.5%). In all demographic and comorbid subgroups associated with microalbuminuria, the prevalence of microalbuminuria increased by 2 to 4 times. A total of 1,743 subjects (17.4%) classified as normoalbuminuric by means of IN were reclassified as microalbuminuric by means of HPLC. Using multivariate logistic regression, women, patients with untreated and treated hypertension, and those with impaired glucose tolerance or diabetes were associated significantly with a change in category from normoalbuminuric to microalbuminuria by means of HPLC.
HPLC measures significantly more urinary albumin within the normoalbuminuria and microalbuminuria range, resulting in a significant increase in prevalence of microalbuminuria. Longitudinal studies are needed to determine whether the extra individuals identified by means of HPLC are at increased risk for developing hard clinical outcomes (renal and cardiovascular).
微量白蛋白尿是普通人群心血管发病和死亡的独立危险因素。标准免疫化学尿白蛋白检测可检测免疫反应性白蛋白,而高效液相色谱法(HPLC)可检测免疫反应性和非免疫反应性白蛋白。
利用澳大利亚糖尿病、肥胖与生活方式队列研究中随机选取的澳大利亚社区成年人群的数据,采用免疫比浊法(IN)和HPLC对随机尿样进行蛋白尿检测(随机尿白蛋白-肌酐比值[ACR]:正常,<30mg/g;微量白蛋白尿,30至300mg/g;大量白蛋白尿,>300mg/g)(n = 10,010)。
Bland-Altman分析显示存在显著偏差,HPLC检测的ACR更高,尤其是在较低ACR水平时。IN检测的平均ACR为15.8mg/g(95%置信区间[CI],12.3至19.2),而HPLC检测的平均ACR为30.0mg/g(95%CI,27.0至35.0)。与IN相比,HPLC检测的微量白蛋白尿患病率高出4倍(20%对5.5%)。在与微量白蛋白尿相关的所有人口统计学和合并症亚组中,微量白蛋白尿患病率增加了2至4倍。共有1743名通过IN检测被分类为正常白蛋白尿的受试者通过HPLC重新分类为微量白蛋白尿。使用多变量逻辑回归分析,女性、未治疗和已治疗的高血压患者以及糖耐量受损或糖尿病患者通过HPLC检测从正常白蛋白尿转变为微量白蛋白尿的类别变化显著相关。
HPLC在正常白蛋白尿和微量白蛋白尿范围内检测到的尿白蛋白显著更多,导致微量白蛋白尿患病率显著增加。需要进行纵向研究以确定通过HPLC识别出的额外个体发生严重临床结局(肾脏和心血管)的风险是否增加。