IgA nephropathy (IgAN) is recognized as the most common immune complex related to the cause of glomerulonephritis worldwide. The disease is characterized by the predominant deposition of underglycosylated IgA1 in the mesangial area of glomeruli. Dysregulation of the immune system plays an important role in the pathogenesis of IgAN. Abnormalities restricted to T lymphocytes and/or B lymphocytes activation could be a critical causative factor in the over-production of underglycosylated IgA1.
Antigen-Antibody Complex ; B-Lymphocytes ; Glomerular Mesangium ; Glomerulonephritis, IGA ; pathology ; Humans ; Immunoglobulin A ; chemistry ; T-Lymphocytes

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.
Adult ; Child ; Comparative Study ; Female ; Glomerular Mesangium/immunology/*pathology ; Hematuria/etiology ; Human ; Immunoglobulin A/*analysis ; Male ; Nephrosis, Lipoid/complications/immunology/*pathology

A total of 394 cases of minimal lesion were reviewed and reassessed clinically and by laboratory investiga- tion, for 4 years from 1979 to 1982. Association with nephrotic syndrome is significantly higher in the cases with histologically normal-appearing mesangium than in the cases with mesangial proliferation. In 43% of the cases of minimal lesion, a minimal but prominent mesangial deposit of Immunoglobulin M with or without C3 deposit was found, and frequently accompanied with nephrotic syndrome, which is not sufficient to accept the condition as a specific disease entity such as "IgM Nephropathy" in our present study. Minimal lesion with a minimal but unmistakable deposit of lgA on the mesangium was noted less frequently and was accompanied or unaccompanied by nephrotic syndrome, a condition which call for an investigation clarify the characteristics and the extent of lgA(Berger's) nephropathy. Response to steroids in minimal lesion nephrotic syndrome was better in children and in the cases without mesangial proliferation, but was unrelated to either hematuria or immunoglobulin deposit. However, the cases with mesangial proliferation are significantly lesser in therapeutic response. Transformation to another morphological type of original glomerular change during follow-up was not observed in 4 available cases of minimal lesion nephrotic syndrome. Henoch-Sch nlein purpura was seen more commonly in children, and lgA(Berger's) nephropathy more commonly in adults.
Adolescent ; Adult ; Cell Division* ; Child ; Complement/analysis* ; Female ; Fluorescent Antibody Technique ; Glomerular Mesangium/pathology* ; Human ; Immunoglobulins/analysis* ; Male ; Nephrosis, Lipoid/pathology* ; Nephrotic Syndrome/pathology*

OBJECTIVETo study the clinicopathologic features of membranous nephropathy coexisting with IgA nephropathy.

METHODSThe 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.

RESULTSThe 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.

CONCLUSIONMembranous nephropathy coexisting with IgA nephropathy possesses the clinicopathologic features of both components. It might be caused by independent occurrence of the two entities.

Adult ; Female ; Glomerular Basement Membrane ; immunology ; pathology ; ultrastructure ; Glomerular Mesangium ; immunology ; pathology ; ultrastructure ; Glomerulonephritis, IGA ; complications ; immunology ; pathology ; Glomerulonephritis, Membranous ; complications ; immunology ; pathology ; Humans ; Immunoglobulin A ; metabolism ; Immunoglobulin G ; metabolism ; Kidney Glomerulus ; immunology ; pathology ; ultrastructure ; Male ; Middle Aged ; Retrospective Studies

OBJECTIVETo determine the effect of hypercholsterolemia induced by a high-lipid diet on glomerulosclerosis.

METHODSTwenty nephrotic syndrome (NS) Wistar rats administrated adriamycin (ADR) with a single intravenous dose of 5 mg/kg body weight, were divided into the standard and high-lipid chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control. Urinary protein excretion and serum cholesterol were assayed; image analysis and techniques of pathology, immunohistochemistry, and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups.

RESULTSThe serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS [(2.2 +/- 0.3) g/L vs. (0.9 +/- 0.1) g/L, P < 0.01] and NS [(9.5 +/- 0.2) g/L vs. (2.3 +/- 0.3) g/L, P < 0.01]. The urinary protein excretion was significantly higher in the high-lipid diet rats than in standard chow rats [(76.2 +/- 24.2) mg/24h vs. (44.8 +/- 13.6) mg/24h, P < 0.05] in NS rats. Although increases in the mesangial matrix and mesangial cells were observed in rats with high-lipid diet in both NS and non-NS group, more obvious pathological changes were found in NS group, such as lipid deposits and foam cell formation in mesangial areas, and progressing to focal and segmental glomerulosclerosis in some glomeruli. The immunohistochemical asay showed that the production of 3 major components (collagen IV, fibronectin, and laminin) was increased in NS group, especially in the rats with high-lipid chow. The increased expression of laminin mRNA was also detected with slot blotting in both NS and non-NS rats with high-lipid chow, and it was more obvious in the rats with NS.

CONCLUSIONOur findings indicated that diet-induced hyperlipidemia can lead to over-production of mesangial matrix components, and further aggravate glomerulosclerosis in ADR-induced nephrosis.

Animals ; Dietary Fats ; pharmacology ; Doxorubicin ; Fibronectins ; metabolism ; Glomerular Mesangium ; metabolism ; pathology ; Hypercholesterolemia ; metabolism ; Laminin ; metabolism ; Male ; Nephrotic Syndrome ; chemically induced ; metabolism ; pathology ; Proteinuria ; urine ; Rats ; Rats, Wistar

BACKGROUND: Transforming growth factor-beta (TGF-beta) stimulates renal fibrosis in various renal diseases including IgA nephropathy. METHODS: We examined whether immunoglobulin A (IgA) stimulated TGF-beta1 synthesis in human mesangial cells (MCs), and whether this effect was mediated through the protein kinase C (PKC) pathway. We measured the intraglomerular TGF-beta1 mRNA expression by using competitive RT-PCR, and this was compared with various parameters in IgA nephropathy patients. RESULTS: The IgA aggregate increased the TGF-beta1 mRNA expression in MCs, while this expression was not affected by the culture media or IgG aggregate. Phorbol 12-myristate 13-acetate and calphostin C did not influence the TGF-beta1 mRNA expression that was increased by the IgA aggregate. Intraglomerular TGF-beta1 mRNA expression was significantly correlated with creatinine clearance (r=-0.764, p=0.027), daily proteinuria (r=0.781, p=0.022), serum creatinine (r=0.884, p=0.004), and tubulointerstitial changes (r=0.809, p=0.015). Glomerular TGF-beta1 mRNA expression was associated with an increased tendency for glomerulosclerosis (r=0.646, p=0.084). After 4 years, patients with a high expression of intraglomerular TGF-beta1 mRNA showed a tendency for an decrease of their renal function. CONCLUSION: The IgA aggregate increased TGF-beta1 mRNA expression in MCs, and this was independent of the PKC pathway. The evaluation of intraglomerular TGF-beta1 mRNA expression could be useful in predicting the progression of IgA nephropathy.
Cells, Cultured ; Female ; Glomerular Mesangium/*cytology/metabolism ; Glomerulonephritis, IGA/metabolism/pathology ; Humans ; Immunoglobulin A/*pharmacology ; Male ; Proteins/*metabolism ; RNA, Messenger/*metabolism ; Research Support, Non-U.S. Gov't

Here we report two cases of isolated diffuse mesangial sclerosis (IDMS) with early onset end-stage renal failure. These female patients did not show abnormalities of the gonads or external genitalia. Direct sequencing of WT1 PCR products from genomic DNA identified WT1 mutations in exons 8 (366 Arg>His) and 9 (396 Asp>Tyr). These mutations have been reported previously in association with Denys-Drash syndrome (DDS) with early onset renal failure. Therefore we suggest that, at least in part, IDMS is a variant of DDS and that investigations for the WT1 mutations should be performed in IDMS patients. In cases with identified WT1 mutations, the same attention to tumor development should be required as in DDS patients, and karyotyping and serial abdominal ultrasonograms to evaluate the gonads and kidney are warranted.
Base Sequence ; DNA/chemistry/genetics ; DNA Mutational Analysis ; Fatal Outcome ; Female ; Glomerular Mesangium/*pathology ; Humans ; Infant ; Infant, Newborn ; *Mutation ; Nephrosclerosis/*genetics ; WT1 Proteins/*genetics

Animals ; Arginine Vasopressin ; physiology ; Connective Tissue Growth Factor ; physiology ; Glomerular Mesangium ; pathology ; Humans ; Integrin alpha1beta1 ; physiology ; Kidney Diseases ; etiology ; Proto-Oncogene Protein c-ets-1 ; physiology

The occurrence of immunoglobulin A nephropathy (IgAN) in patients with noninsulin dependent diabetes mellitus (NIDDM) is a rare event and of pathogenetic interest. It is not clear whether this is merely coincidence. We report here five patients with IgAN in NIDDM associated with or without diabetic glomerulosclerosis. All of the patients were Korean males. In three patients, diabetes mellitus was diagnosed at the same time with diagnosis of IgAN, and the known duration of the diabetes in the other two patients were three and seven years, respectively. There was no evidence of diabetic retinopathy in four patients, but it was found in one patient. In all cases, the diagnosis of IgAN was made by immunohistology.
Adult ; Biopsy ; Case Report ; Complement 3/analysis ; Diabetes Mellitus, Non-Insulin-Dependent/complications* ; Diabetic Nephropathies/pathology* ; Glomerular Mesangium/pathology ; Glomerulonephritis, IGA/pathology* ; Glomerulonephritis, IGA/etiology ; Human ; IgG/analysis ; Kidney Glomerulus/pathology ; Male ; Microscopy, Fluorescence ; Middle Age

OBJECTIVETo explore whether there is phenotypic modulation of mesangial cells in streptozotocin (STZ) induced diabetic rats and study the effect of Tujian Mixture (TJM) on it.

METHODSSD rats were divided into the normal control group (NC group, n = 8), the unilateral nephrectomized control group (QC group, n = 8), the STZ induced diabetes mellitus with unilateral nephrectomy model group (DM group, n = 8), the Valsartan treated group (VT group, n = 8) and the TJM treated group (ZY group, n = 9), rats in the latter two groups were modeled as in the DM group and treated with Valsartan (20 mg/kg.d) and TJM (20 g/kg.d) respectively for 12 weeks. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta 1 (TGF-beta 1) in rats glomeruli were observed by immunohistochemistry assay, and the ratio of alpha-SMA and TGF-beta 1 positive area/total glomerule tuft area (SMA/GT and TGF/GT) were analyzed using computer-assisted image analysis software.

RESULTSIn the NC and the QC groups, only trace of alpha-SMA positive staining was found. But there was prominant alpha-SMA positive staining in glomeruli of the DM group, with SMA/GT and TGF/GT increased significantly (P < 0.01), and marked increase of 24 hrs proteinuria excretion (P < 0.01). As compared with the DM group, the three indexes were all significantly lower in the VT and ZY groups (P < 0.01), and the lowering of proteinuria was more significant in the ZY group than that in the VT group (P < 0.01).

CONCLUSIONThe expression of alpha-SMA in glomeruli in STZ induced diabetic rats with unilateral nephrectomy is pronounced, indicating that phenotypic modulation of mesangial cells involvement in the pathogenesis of diabetic nephropathy. TJM and Valsartan can reduce 24 hrs proteinuria excretion, inhibit the phenotypic modulation of mesangial cells and the expression of TGF-beta 1 in glomeruli of diabetic rats, and the effect of TJM is more potent than that of Valsartan in lowering urinary protein excretion.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Diabetic Nephropathies ; etiology ; metabolism ; pathology ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; Glomerular Mesangium ; metabolism ; pathology ; Image Processing, Computer-Assisted ; Male ; Nephrectomy ; Phenotype ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta ; metabolism