Banu N, Hara H, Egusa G, Yamakido M
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Hiroshima J Med Sci. 1994 Dec;43(4):123-33.
We investigated the role of measurement of serum and urinary type IV collagen (IV-C) levels in monitoring diabetic microangiopathy. Furthermore, we compared these levels in diabetic nephropathy and non-diabetic renal disease (NDRD). A one-step sandwich enzyme immunoassay was used to measure IV-C levels in 82 diabetic patients, 33 NDRD patients and 20 healthy non-diabetic control subjects. The diabetic patients were classified into four groups according to urinary albumin/creatinine index (ACI) (mg/g) and serum creatinine (s-Cr) (mg/dl): normoalbuminuria (ACI < 30), microalbuminuria (ACI 30-300), albuminuria (ACI > 300, s-Cr < 1.99 mg/dl) and renal insufficiency (s-Cr > 1.99 mg/dl). Serum and urinary IV-C levels were significantly elevated even in diabetic patients without clinical evidence of microangiopathy compared with control subjects (p < 0.05 and p < 0.01, respectively). Both levels were significantly higher in normoalbuminuric patients than in the control subjects, and in patients with microalbuminuria, albuminuria or renal insufficiency than in normoalbuminuric patients, with significant differences between these groups (serum and urinary IV-C, both p < 0.0001 by ANOVA). Urinary IV-C and albumin levels were significantly correlated, even in normo- and microalbuminuric patients (r = 0.55, p < 0.0001). Serum IV-C in normoalbuminuric patients rose significantly as the degree of retinopathy progressed from background to proliferative stages (p < 0.05). Neither serum nor urinary IV-C levels were influenced by glycemic control. Albuminuric diabetic patients (with and without renal insufficiency) had significantly higher levels of serum IV-C compared with those in proteinuric NDRD patients (p < 0.005), though there was no significant difference in the urinary IV-C level. However, the urinary IV-C/albumin ratio was significantly higher in albuminuric diabetic patients than in proteinuric NDRD patients, even after adjusting for s-Cr and creatinine clearance (p < 0.0001). In conclusion, we suggest that measured serum and urinary IV-C concentrations may serve as new markers for monitoring the development and progression of diabetic microangiopathy, particularly nephropathy. Furthermore, the measurement of serum IV-C concentrations and urinary IV-C/albumin ratios in diabetic patients may allow diabetic nephropathy and non-diabetic renal disease to be differentiated.
我们研究了血清和尿Ⅳ型胶原（IV-C）水平测定在监测糖尿病微血管病变中的作用。此外，我们比较了糖尿病肾病和非糖尿病性肾脏疾病（NDRD）患者的这些水平。采用一步夹心酶免疫分析法测定了82例糖尿病患者、33例NDRD患者和20例健康非糖尿病对照者的IV-C水平。根据尿白蛋白/肌酐指数（ACI）（mg/g）和血清肌酐（s-Cr）（mg/dl）将糖尿病患者分为四组：正常白蛋白尿（ACI＜30）、微量白蛋白尿（ACI 30 - 300）、白蛋白尿（ACI＞300，s-Cr＜1.99 mg/dl）和肾功能不全（s-Cr＞1.99 mg/dl）。与对照组相比，即使在无微血管病变临床证据的糖尿病患者中，血清和尿IV-C水平也显著升高（分别为p＜0.05和p＜0.01）。正常白蛋白尿患者的这两个水平均显著高于对照组，微量白蛋白尿、白蛋白尿或肾功能不全患者的水平高于正常白蛋白尿患者，这些组间存在显著差异（血清和尿IV-C，方差分析均为p＜0.0001）。即使在正常白蛋白尿和微量白蛋白尿患者中，尿IV-C和白蛋白水平也显著相关（r = 0.55，p＜0.0001）。随着视网膜病变程度从背景期进展到增殖期，正常白蛋白尿患者的血清IV-C显著升高（p＜0.05）。血糖控制对血清和尿IV-C水平均无影响。白蛋白尿糖尿病患者（有和无肾功能不全）的血清IV-C水平显著高于蛋白尿性NDRD患者（p＜0.005），尽管尿IV-C水平无显著差异。然而，即使在调整s-Cr和肌酐清除率后，白蛋白尿糖尿病患者的尿IV-C/白蛋白比值仍显著高于蛋白尿性NDRD患者（p＜0.0001）。总之，我们认为所测血清和尿IV-C浓度可作为监测糖尿病微血管病变尤其是肾病发生和进展的新标志物。此外，测定糖尿病患者的血清IV-C浓度和尿IV-C/白蛋白比值可能有助于鉴别糖尿病肾病和非糖尿病性肾脏疾病。
