Background and Object IgA nephropathy is the most common primary glomerulonephritis worldwide and a major cause of end stage renal disease (ESRD).Therefore, it is important to exactly estimate the prognosis and to study the progressive mechanism of IgA nephropathy. In this study, we explored the relationship between renal function and histological indexes, and studied the role of microvascular lesions in IgA nephropathy progression and its association to plasminogen activator system.Methods (1) By rank-order correlation and ordinal logistic regression analysis of 861 IgA nephropathy patients' clinicopathological data, the histological indexes exactly associated with glomerular filtration rate (GFR) stage were selected. Based on total score's distribution by GFR stage of the selected histology lesions a new histological grading system was set up, whose sensitivity and specificity for IgA nephropathy GFR stage were compared with traditional Lee's grading system using the ROC curve method. (2) 20 renal glomeruli or 200 renal tubules and peritubular interstitial per patient were captured by Laser Microdissection System from IgA nephropathy renal biopsy slides (8μm). Plasminogen activator (PA) mRNA and plasminogen activator inhibitor-1 (PA1-1) mRNA levels in glomerulus and tubulointerstitial area were measured by Taqman quantitative real-time PCR. Capillaries densities and PA/PAI-1 protein expressions in glomerulus and tubulointerstitial area were measured using immunohistological staining method and computer image analyses system. The associations between PA/PAI mRNA and capillaries densities were analyzed using linear regression analysis.Results (1) Glomerular global sclerosis, tubular atrophy, interstitial fibrosis and vascular lesions were correlated with IgA nephropathy GFR stages at multivariate and univariate analysis. The histological grading system based on the total score of glomerular global sclerosis, tubular atrophy, interstitial fibrosis and vascular...
|