Ellis D, Forrest K Y, Erbey J, Orchard T J
Division of Nephrology, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, PA 15213, USA.
Clin Chem. 1998 May;44(5):950-6.
Urinary samples were concentrated rapidly and efficiently and were used to develop several protein assays that may be of value in monitoring individuals with progressive renal disorders. Transforming growth factor-beta1 (TGF-11) and retinol binding protein (RBP) were measured with modification of commercially available methods used to assay serum specimens; type 3 collagen (T3C) was measured with a new immunonephelometric assay. The precision characteristics of these assays are comparable with those reported for microalbuminuria. The clinical utility of measuring a panel of these markers was demonstrated in urine samples from 16 control subjects and from 46 individuals with insulin-dependent diabetes mellitus (IDDM) with various albumin excretion rates (AERs). TGF-beta1 and T3C were used as markers of cytokine expression and of the renal fibrogenic process, whereas RBP excretion served as a marker of tubular injury or dysfunction. Compared with controls, T3C excretion was significantly increased in 18 normoalbuminuric and further increased in 13 microalbuminuric (AER 20 < or = 200 microg/min) IDDM subjects. RBP excretion was increased in macroalbuminuric IDDM subjects (AER >200 microg/min, overt nephropathy). Significant correlations were also found between AER and RBP in all but macroalbuminuric individuals, whereas TGF-beta1 correlated with T3C excretion in controls and in normoalbuminuric diabetic subjects. Urinary RBP but not AER was an excellent predictor of diabetic nephropathy as defined by serum creatinine (P = 0.0001). This underscores the importance of an early tubulopathy in the subsequent development of glomerulopathy and overt nephropathy. The data suggest that longitudinal monitoring of a panel of urinary markers such as that used in the current study may better define their relevance in progressive glomerulosclerosis and may also provide greater insight into the mechanisms underlying such process.
尿样被快速有效地浓缩，并用于开发几种蛋白质检测方法，这些方法可能对监测进行性肾脏疾病患者有价值。转化生长因子-β1（TGF-11）和视黄醇结合蛋白（RBP）通过对用于检测血清标本的市售方法进行改良来测定；Ⅲ型胶原（T3C）用一种新的免疫比浊法测定。这些检测方法的精密度特性与报道的微量白蛋白尿检测方法相当。在16名对照受试者和46名不同白蛋白排泄率（AER）的胰岛素依赖型糖尿病（IDDM）患者的尿样中，证明了检测一组这些标志物的临床实用性。TGF-β1和T3C用作细胞因子表达和肾脏纤维化过程的标志物，而RBP排泄用作肾小管损伤或功能障碍的标志物。与对照组相比，18名正常白蛋白尿的IDDM患者T3C排泄显著增加，13名微量白蛋白尿（AER 20≤200μg/min）的IDDM患者进一步增加。大量白蛋白尿的IDDM患者（AER>200μg/min，显性肾病）RBP排泄增加。除大量白蛋白尿个体外，在所有个体中AER与RBP之间也发现显著相关性，而在对照组和正常白蛋白尿糖尿病患者中TGF-β1与T3C排泄相关。尿RBP而非AER是血清肌酐定义的糖尿病肾病的优秀预测指标（P = 0.0001）。这强调了早期肾小管病变在随后肾小球病变和显性肾病发展中的重要性。数据表明，如本研究中所用的对一组尿标志物进行纵向监测，可能更好地确定它们在进行性肾小球硬化中的相关性，也可能更深入地了解该过程的潜在机制。
