Mackinnon B, Shakerdi L, Deighan C J, Fox J G, O'Reilly D St J, Boulton-Jones M
Renal Unit, Glasgow Royal Infirmary, Glasgow, Scotland.
Clin Nephrol. 2003 Apr;59(4):252-8. doi: 10.5414/cnp59252.
Proteinuria predicts rate of progression in a variety of nephropathies. There is considerable evidence that iron-transferrin is toxic to proximal tubular cells in vitro, and recent clinical work suggests that selectivity of proteinuria influences the outcome of renal disease. The aim of this study was to examine the relationship between the nature of proteinuria and progression of renal disease.
This was a prospective, cross-sectional study in 66 patients with primary glomerulonephritis, diabetic nephropathy and a variety of other renal diseases. Urinary transferrin was measured by sandwich ELISA and correlated with rate of change in estimated creatinine clearance (ECC). Urinary SDS-PAGE was undertaken to divide proteinuria into tertiles according to molecular weight and to quantify the protein in each tertile. The magnitude of each tertile was then correlated with rate of change in ECC over a median period of 20 months.
Rate of change of renal function correlated with total proteinuria (r2 = 18%, p < 0.001) and albuminuria (r2 = 17%, p < 0.001), but not urinary transferrin (r2 = 0%, p = 0.235). On univariate analysis high molecular weight proteinuria (r2 = 21%, p < 0.001), intermediate molecular weight proteinuria (r2 = 15%, p = 0.001) and low molecular weight proteinuria (r2 = 10%, p = 0.005) correlated with rate of change in ECC as did total fasting cholesterol (r2 = 7%, p = 0.003). On multivariate analysis, however, the only independent predictors of rate of change in ECC were high molecular weight proteinuria (r2 = 19%, p < 0.001), and total fasting cholesterol (r2 = 5%, p = 0.035).
We found no evidence to support the hypothesis that iron-transferrin is important in the development of human renal injury. High molecular weight proteinuria correlates more strongly with rate of progression of renal disease than intermediate molecular weight, low molecular weight or even total proteinuria. This suggests either, that one or more high molecular weightproteins are implicated in causing progressive renal impairment, or that loss of size selectivity at the glomerular basement membrane is associated with accelerated tubulointerstitial damage.
蛋白尿可预测多种肾病的进展速度。有大量证据表明，铁转铁蛋白在体外对近端肾小管细胞有毒性，并且最近的临床研究表明蛋白尿的选择性会影响肾脏疾病的预后。本研究的目的是探讨蛋白尿的性质与肾脏疾病进展之间的关系。
这是一项针对66例原发性肾小球肾炎、糖尿病肾病及其他多种肾脏疾病患者的前瞻性横断面研究。采用夹心酶联免疫吸附测定法检测尿转铁蛋白，并将其与估计的肌酐清除率（ECC）的变化率进行相关性分析。进行尿十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳（SDS - PAGE），根据分子量将蛋白尿分为三分位数，并对每个三分位数中的蛋白质进行定量。然后将每个三分位数的大小与20个月中位数期间ECC的变化率进行相关性分析。
肾功能变化率与总蛋白尿（r2 = 18%，p < 0.001）和白蛋白尿（r2 = 17%，p < 0.001）相关，但与尿转铁蛋白无关（r2 = 0%，p = 0.235）。单因素分析显示，高分子量蛋白尿（r2 = 21%，p < 0.001）、中分子量蛋白尿（r2 = 15%，p = 0.001）和低分子量蛋白尿（r2 = 10%，p = 0.005）与ECC变化率相关，空腹总胆固醇也与之相关（r2 = 7%，p = 0.003）。然而，多因素分析显示，ECC变化率的唯一独立预测因素是高分子量蛋白尿（r2 = 19%，p < 0.001）和空腹总胆固醇（r2 = 5%，p = 0.035）。
我们没有发现证据支持铁转铁蛋白在人类肾损伤发生中起重要作用的假设。高分子量蛋白尿与肾脏疾病进展速度的相关性比中分子量、低分子量蛋白尿甚至总蛋白尿更强。这表明，要么是一种或多种高分子量蛋白质与进行性肾功能损害有关，要么是肾小球基底膜大小选择性的丧失与肾小管间质损伤加速有关。
