Hirano T, Ookubo K, Kashiwazaki K, Tajima H, Yoshino G, Adachi M
First Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan.
Clin Chim Acta. 2000 Sep;299(1-2):65-75. doi: 10.1016/s0009-8981(00)00274-6.
To elucidate the hypothesis that albuminuria in diabetic subjects reflects widespread vascular damage, plasma markers for vascular endothelial damage was measured in diabetic subjects with various degrees of albuminuria and compared to results in patients with primary renal disease. The groups consisted of 31 non-diabetic patient controls with normoalbuminuria, 109 type 2 diabetic patients with normo- micro- and macro-albuminuria, and 16 proteinuric patients with primary renal disease. Endothelial markers, plasma von Willebrand factor (vWF) and thrombomodulin (TM), were measured by enzyme-linked immunosolvent assay and enzyme immunoassay (EIA) methods, respectively. Plasma vWF levels were similar in controls (119+/-7%, mean+/-S.E.M.) and diabetic patients with normoalbuminuria (139+/-6), but significantly elevated in diabetic patients with microalbuminuria (174+/-11) and macroalbuminuria (204+/-17), while the level was not increased in patients with primary renal disease (124+/-11). Because plasma TM level was strongly affected by kidney function, TM index (TM (FU/ml)/serum creatinine (mg %)) was used as an endothelial marker. The TM index was substantially increased in diabetic patients with overt nephropathy compared with controls (5.29+/-2.98 vs. 2.35+/-0.85), whereas this was not observed in patients with primary renal disease (3.25+/-0.29). Both vWF and TM index were significantly higher in diabetic patients with retinopathy than in the patients without retinopathy. These results suggest that generalized vascular endothelial damage occurs in diabetic nephropathy including the microalbuminuric stage, which is not attributed to kidney damage per se.
为了阐明糖尿病患者蛋白尿反映广泛血管损伤这一假说，我们测定了不同程度蛋白尿的糖尿病患者血管内皮损伤的血浆标志物，并与原发性肾病患者的结果进行比较。研究组包括31例正常白蛋白尿的非糖尿病患者对照、109例2型糖尿病正常白蛋白尿、微量白蛋白尿和大量白蛋白尿患者，以及16例原发性肾病的蛋白尿患者。内皮标志物血浆血管性血友病因子（vWF）和血栓调节蛋白（TM）分别采用酶联免疫吸附测定法和酶免疫测定法（EIA）进行测定。对照组（119±7%，平均值±标准误）和正常白蛋白尿的糖尿病患者血浆vWF水平相似（139±6），但微量白蛋白尿（174±11）和大量白蛋白尿（204±17）的糖尿病患者显著升高，而原发性肾病患者（124±11）的水平未升高。由于血浆TM水平受肾功能的强烈影响，TM指数（TM（FU/ml）/血清肌酐（mg%））被用作内皮标志物。与对照组相比，显性肾病的糖尿病患者TM指数显著升高（5.29±2.98对2.35±0.85），而原发性肾病患者未观察到这种情况（3.25±0.29）。有视网膜病变的糖尿病患者的vWF和TM指数均显著高于无视网膜病变的患者。这些结果表明，包括微量白蛋白尿阶段在内的糖尿病肾病中存在全身性血管内皮损伤，这并非归因于肾脏损伤本身。
