Twenty-five cases of minimal change nephrotic syndrome(minimal change disease, MCD) with mesangial IgA deposition were evaluated electron microscopically. The thickness of the glomerular basement membrane(GBM) was 3875 +/- 1271 A and 3056 +/- 1201 A in adults and children, respectively. Alteration of the GBM was noted in 3 adults and eight children: splitting in 4, focal thinning in one, widening of the lamina rara interna in 10, and widening of the lamina rara externa in 4 cases. Minimal mesangial electron dense deposits were found in all but one adult, and an increase of the mesangial matrix and minimal mesangial proliferation were observed in 8 and 6 cases, respectively. Electron microscopic findings show representative findings of MCD in our cases. A relationship between the GBM alterations in these cases and frequent association of hematuria is suggested and discussed.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Glomerular Mesangium/*metabolism ; Human ; Immunoglobulin A/*metabolism

Leptospirosis is a spirochaetal infectious disease caused by Leptospira interrogans. Multiple organ involvement may be encountered in leptospirosis. Early renal involvement is very common and characterized by tubulo-interstitial nephritis and tubular dysfunction. Rarely, diffuse mesangial proliferative glomerulonephritis may be seen. Immunoglobulin A nephropathy (IgA nephropathy) is defined by the predominant deposition of IgA in the glomerular mesangium. The secondary IgA nephropathy is thought to be caused by hepatobiliary disease, mucosal disease, infection, malignancy, some hematologic disease and systemic autoimmune or hypersensitivity disease. However, there are few reports about IgA nephropathy associated with leptospirosis. We herein report a case of IgA nephropathy in 21-year- old leptospirosis patient.
Communicable Diseases ; Glomerular Mesangium ; Glomerulonephritis ; Glomerulonephritis, IGA* ; Hematologic Diseases ; Humans ; Hypersensitivity ; Immunoglobulin A* ; Leptospira interrogans ; Leptospirosis* ; Nephritis

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

In this paper, 2 cases of collagen Type Ⅲ glomerulopathy were analyzed. The clinical manifestations mainly included nephrotic syndrome, proteinuria, hypertension and renal dysfunction. One patient showed that the complement factor H-related protein 5 (CFHR5) gene was likely a disease-causing mutation. The pathological examination of renal tissues showed hyperplasia of mesangial matrix, sub-endothelial insertion, and double-track formation. Immunohistochemistry of Type III collagen was positive. Electron microscopy revealed that massive collagen fibers (40-70 nm in diameter) deposited in the mesangial matrix and basement membrane. As for the follow-up results, the normal renal function had kept steady and the proteinuria was moderate in 1 case treated with angiotensin Ⅱ receptor blocker. Due to other system disease, another case developed into acute kidney injury and then received hemodialysis. The clinical manifestations of collagen Type Ⅲ glomerulopathy was atypical, the light microscope pathological features were various, and the disease was mainly diagnosed by electron microscopy and immunohistochemistry.
Collagen Type III ; genetics ; Glomerular Mesangium ; Humans ; Kidney Diseases ; Kidney Glomerulus ; Proteinuria

OBJECTIVES: To investigate the possible role of mononuclear cells and their products in the pathogenesis of IgA nephropathy, in vitro expression of ICAM-1 on cultured mouse mesangial cell (MC) was examined after stimulation with mononuclear cell culture supernatant from patients with IgA nephropathy. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated and cultured from 18 patients with primary IgA nephropathy, 8 normal controls and 5 patients with non-IgA nephropathy (FSGS 1, MGN 3, MPGN 1). ICAM-1 expression on cultured mouse MC by TNF-alpha, IL-1 beta and culture supernants of PBMC were analyzed using a cell ELISA method. The concentration of IL-1 beta and TNF-alpha in culture supernatants was measured by using a commercially available radioimmunoassay kit. RESULTS: Addition of human recombinant TNF-alpha induced an increased ICAM-1 expression in a dose-dependent manner. The expression of ICAM-1 was further increased after co-stimulation with TNF-alpha and IL-1 beta. Addition of PBMC culture supernatants into mouse MC induced significantly higher expression of ICAM-1 by supernatants from the patients with IgA nephropathy compared with that from normal controls. The concentration of TNF-alpha and IL-1 beta in supernatants from the patients with IgA nephropathy was significantly higher than that from those with non-IgA nephropathy. CONCLUSION: TNF-alpha and IL-1 released from mononuclear cells induced the up-regulation of ICAM-1 expression and this may be related to the immune pathogenesis of IgA nephropathy.
Animal ; Cells, Cultured ; Glomerular Mesangium/immunology ; Glomerular Mesangium/cytology ; Glomerulonephritis, IGA/immunology* ; Glomerulonephritis, IGA/etiology ; Human ; Intercellular Adhesion Molecule-1/metabolism* ; Interleukin-1/secretion ; Interleukin-1/pharmacology ; Leukocytes, Mononuclear/immunology ; Mice ; Tumor Necrosis Factor/secretion ; Tumor Necrosis Factor/pharmacology

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*

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