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Objective: To further improve the recognition of Alport syndrome., Methods: The patients with COL4A3, COL4A4 or COL4A5 mutations, admitted to Department of Pediatric, Peking University First Hospital from 2005 to 2009, were retrospectively studied. Their clinical and ultrastructural characteristics were compared between the male patients with X-linked dominant inheritance Alport syndrome (XLAS) and the patients with autosomal recessive inheritance Alport syndrome (ARAS)., Results: There were 54 male patients with XLAS and 14 patients with ARAS. Compared with the male patients with XLAS, episodic gross hematuria was prominent (P<0.001) in patients with ARAS. Family history was also different between the two groups (P=0.016). However, there was no significant difference in the age of identification of symptoms, initial manifestations, levels of proteinuria, extrarenal signs and ultra-structural glomerular basement membrane changes between the two groups., Conclusion: There are some features that distinguish between the patients with XLAS and the patients with ARAS.

Objective: To analyse the relationship of ultrastructural changes of glomerular basement membrane (GBM) and glomerular distributions of laminin alpha1 and laminin alpha5 in patients with Alport's syndrome., Methods: Twenty patients with Alport's syndrome were recruited. The thickness of GBM and the extension of thickening and splitting GBM were measured under transmission electron microscope. Normal renal tissues from 6 nephrectomies of renal carcinoma were taken as controls. Paraffin embedded sections of formalin-fixed renal tissue were processed for immunohistochemistry with monoclonal antibodies to laminin alpha1 and laminin alpha5. Their distributions in GBM were evaluated by a semiquantitative scale of positive extension: absent, 0; < or =25%, 1; 25%-50%, 2; 50%-75%, 3; > or =75%, 4., Results: There were a variety of degrees of thickening or splitting GBM in patients with Alport's syndrome. Laminin alpha1 was positive in glomerular mesangial area and absolutely negative in GBM and laminin alpha5 was evenly positive in GBM in normal tissue. In Alport's syndrome, laminin alpha1 was much weaker in glomerular mesangial area, but strongly positive in GBM; laminin alpha5 in GBM was prominently reduced. There was a high negative correlation of semiquantitative scores between laminin alpha1 and laminin alpha5 (r=-0.83, P<0.001). The extension of thickening or splitting GBM was positively correlated with scores of laminin alpha1 in GBM (r=0.76, P<0.001; r=0.56, P=0.015), and was negatively correlated with scores of laminin alpha5 in GBM (r=-0.59, P=0.010; r=-0.53, P=0.025)., Conclusion: Abnormal distribution of laminin alpha1 and laminin alpha5 in GBM is correlated with GBM thickening and splitting in human Alport's syndrome.

Objective: To study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy., Methods: The renal biopsies performed in Peking University First Hospital during the period from January, 1998 to April, 2006 were retrospectively reviewed. The clinicopathologic features of 11 cases of membranous nephropathy coexisting with IgA nephropathy were studied. Electron microscopy with immunogold labeling for IgG and IgA were also performed., Results: The mean age of patients was 39.9 years. The male-to-female ratio was 1:2.9. The patients mainly presented with proteinuria. Proteinuria of nephrotic level was seen in 7 cases (63.6%). Seven cases also had associated microscopic hematuria. None of them showed evidence of renal insufficiency. Cases with secondary diseases, such as hepatitis virus infection and systemic lupus erythematosus, were excluded from the study. Histologically, vacuolation and thickening of glomerular basement membrane was seen. There was also mild mesangial hypercellularity and increase in mesangial matrix. Occasional glomeruli with crescent formation were identified in 2 cases. Immunofluorescence study showed granular staining for IgG and C3 along glomerular capillary walls, in addition to clumps of IgA deposits in mesangium. Electron microscopy revealed subepithelial and mesangial electron-dense deposits. Immunogold labeling showed IgG and IgA localized in the subepithelial and mesangial deposits respectively., Conclusion: Membranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Objective: To study the morphologic changes of collagen type III glomerulopathy and to investigate the possible cellular origin for collagen III production., Methods: Light microscopy, immunofluorescent staining, immunohistochemistry (for collagen I, III and IV and alpha-SMA) and electron microscopy studies on 3 renal biopsy cases of collagen type III glomerulopathy were performed., Results: Two cases presented with nephrotic syndrome, one of which was associated with systemic hypertension. The third case showed renal impairment and renal hypertension. None had any known family history of renal diseases. Light microscopy showed diffuse thickened glomerular basement membrane and expanded mesangium with deposition of weakly PAS-positive homogeneous material not associated with mesangial cell proliferation. Electron microscopy revealed massive collagen fiber deposits in the subendothelial spaces and mesangium. The mesangial cells also contained bundles of microfilaments in the subplasmalemmal regions. Immunohistochemically, the diffuse positivity for type III collagen corresponded to the homogeneous material seen under light microscopy. The staining for type I and IV collagens was negative. Alpha-SMA was expressed in many mesangial cells., Conclusions: The diagnosis of collagen type III glomerulopathy can be made on the basis of detailed morphologic examination and ancillary investigations. It is possible that activated mesangial cells may be the cellular origin of collagen III.