Bazzi C
U.O. Nefrologia e Dialisi, Azienda Ospedaliera, Ospedale San Carlo Borromeo, Milano, Italy.
G Ital Nefrol. 2003 Jul-Aug;20(4):346-55.
Experimental and clinical studies show that proteinuria is an independent risk factor for the progression of chronic glomerular diseases and is associated with the extent of tubulo-interstitial damage. The accumulation of proteins in tubular cells induces the increased expression of a variety of inflammatory and fibrogenic cytokines, with the consequent development of interstitial inflammation, a proliferation of fibroblasts, the increased production of extracellular matrix, and the formation of interstitial fibrosis. Laboratory methods, such as immunonephelometry, can easily evaluate the glomerular component of proteinuria, due to the alteration of the structural integrity of the glomerular capillary wall. This alteration allows the tubular lumen to pass proteins of high and middle molecular weight (HMW and MMW proteins: IgM, alpha2-macroglobulin, IgG, transferrin, albumin). Using the same method and SDS-PAGE, it is possible to evaluate those tubular components of proteinuria that are composed of low molecular weight (LMW) proteins, such as alpha1-microglobulin (alpha1m) and beta2-microglobulin (beta2m), whose reabsorption by tubular cells-almost complete in physiological conditions-is impaired in pathological conditions. Recent studies clarified some aspects of the relationships between the components of proteinuria, histological lesions, prediction of outcome, and response to therapy. The extent of tubulo-interstitial damage is correlated with selectivity of proteinuria and IgG excretion, suggesting a possible tubulo-toxic role for IgG or for some other protein of similar molecular weight. The tubulo-interstitial lesions are also correlated with the excretion of LMW proteins, due to their impaired reabsorption. The remission of nephrotic syndrome, not predicted by the amount of proteinuria, is highly predicted by the selectivity index or IgG excretion in membranous glomerulonephritis (MGN) and focal segmental glomerulosclerosis (FSGS). Progression to chronic renal failure is better predicted both by the glomerular component (selectivity index, IgG excretion) and by the tubular component of proteinuria (alpha1m, beta1m, LMW proteins), than by 24-hour proteinuria. The response to therapy in MGN and FSGS is dependent on the excretion of IgG and alpha1m. In conclusion the composition of proteinuria can easily be assessed using automated methods, and it is useful to evaluate the relationship of proteinuria with histological lesions to predict the functional outcome and response to therapy in primary glomerulonephritis.
实验和临床研究表明，蛋白尿是慢性肾小球疾病进展的独立危险因素，且与肾小管间质损伤程度相关。蛋白质在肾小管细胞中的蓄积会诱导多种炎症和纤维化细胞因子表达增加，进而导致间质炎症、成纤维细胞增殖、细胞外基质产生增多以及间质纤维化形成。由于肾小球毛细血管壁结构完整性的改变，免疫比浊法等实验室方法能够轻松评估蛋白尿的肾小球成分。这种改变使得肾小管腔能够通过高分子量和中分子量蛋白质（HMW和MMW蛋白质：IgM、α2-巨球蛋白、IgG、转铁蛋白、白蛋白）。使用相同方法和SDS-PAGE，可以评估由低分子量（LMW）蛋白质组成的蛋白尿肾小管成分，如α1-微球蛋白（α1m）和β2-微球蛋白（β2m），在生理条件下肾小管细胞对它们的重吸收几乎是完全的，但在病理条件下会受损。最近的研究阐明了蛋白尿成分、组织学病变、预后预测以及对治疗反应之间关系的一些方面。肾小管间质损伤程度与蛋白尿选择性及IgG排泄相关，提示IgG或某些分子量相似的其他蛋白质可能具有肾小管毒性作用。肾小管间质病变也与LMW蛋白质的排泄相关，因为它们的重吸收受损。在膜性肾小球肾炎（MGN）和局灶节段性肾小球硬化（FSGS）中，肾病综合征的缓解并非由蛋白尿的量预测，而是高度由选择性指数或IgG排泄预测。与24小时蛋白尿相比，蛋白尿的肾小球成分（选择性指数、IgG排泄）和肾小管成分（α1m、β1m、LMW蛋白质）对慢性肾衰竭进展的预测更好。MGN和FSGS对治疗的反应取决于IgG和α1m的排泄。总之，使用自动化方法可以轻松评估蛋白尿的组成，评估蛋白尿与组织学病变的关系对于预测原发性肾小球肾炎的功能结局和对治疗的反应是有用的。
