Adult ; Female ; Humans ; Kidney Glomerulus ; metabolism ; pathology ; Lipoproteins ; metabolism ; Male ; Nephrosis, Lipoid ; metabolism ; pathology

Animals ; Extracellular Matrix ; metabolism ; Humans ; Kidney Glomerulus ; pathology ; Matrix Metalloproteinase 2 ; analysis ; physiology ; Sclerosis

OBJECTIVETo investigate the prevalence of PLA2R1 in renal biopsy specimens of patients with idiopathic membranous nephropathy (IMN) and explore the relationship between PLA2R1 and IMN.

METHODSA total of 108 adult patients with biopsy-proved glomerular diseases were enrolled in this study, including 41 with IMN, 2 with hepatitis B-associated membranous nephropathy, 8 with V lupus nephritis, 27 with IgA nephropathy, 19 with minimal change nephropathy, 5 with mild mesangial proliferative glomerulonephritis, and 6 with focal segmental glomeruloselerosis (FSGS). Indirect immunofluorescence assay was used to detect PLA2R1 in the biopsy specimens and the clinical variables of the IMN patients were analyzed.

RESULTSIn 35 of the 41 (85.37%) patients with IMN, PLA2R1 was detected with a fine granular pattern in the subepithelial deposits along the glomerular capillary loops. PLA2R1 antigen was not detected in patients with other glomerulopathies. No significant differences were found in age, serum creatinine, serum albumin, or 24-h urinary protein level between PLA2R1-positive and negative patients with IMN (P>0.05).

CONCLUSIONAccording to our results, 85.37% of adult patients with biopsy-proven IMN are positive for PLA2R1 antigen, which, however, does not contribute to variations of the patients' clinical manifestations.

Adult ; Biopsy ; Glomerulonephritis, Membranous ; metabolism ; Humans ; Kidney ; metabolism ; pathology ; Kidney Function Tests ; Kidney Glomerulus ; pathology ; Nephrosis, Lipoid ; metabolism ; Receptors, Phospholipase A2 ; metabolism

BACKGROUNDLipoprotein glomerulopathy (LPG), once recognized as a rare glomerular disease, has been reported around the world in recent years. In this study, we reported 8 patients of LPG and aimed to explore the clinical features and pathological characteristics of LPG under light microscope, immunofluorescence staining, and electron microscope.

METHODSClinical manifestations were recorded on the day of renal biopsy. Biochemical patterns of lipids and lipoproteins were detected by routine examination. Plasma concentrations of apo B and apo E were determined by radial immunodiffusion assays. Biopsy specimens were then processed for light microscopy, immunohistochemical staining for immunoglobulins and complement components, and electron microscopy. Glomerular deposition of apo A, B, and E were detected using monoclonal antibodies on cryostatic sections.

RESULTSAll of the eight patients presented with edema, microscopic hematuria, severe proteinuria, anemia, and enlarged kidney size. Biochemical profiles revealed high levels of triglycerides, apo B, and apo E. We noted increments of glomerular size and lipoprotein thrombi occupying capillary lumina in the glomeruli of all patients. Immunofluorescence staining showed that the thrombi were strongly positive for apo A, B, and E. Granules and various sizes of vacuoles were observed in the thrombi under electron microscope.

CONCLUSIONCompared with previous reports on LPG in other countries, unique clinical and pathological features were found in this group of Chinese LPG patients.

Adolescent ; Adult ; Child ; Female ; Humans ; Kidney Diseases ; pathology ; Kidney Glomerulus ; pathology ; ultrastructure ; Lipoproteins ; metabolism ; Male ; Microscopy, Fluorescence ; Middle Aged

OBJECTIVETo investigate the clinicopathological manifestations of early renal amyloidosis (AL) and its diagnostic criteria.

METHODSFifteen cases with early renal amyloidosis admitted from 1994 to 2001 were collected from the hospital, and their clinical and pathological features were reviewed. Of them, the initial diagnoses were not made by depending findings from the light microscopy (LM) and immunofluorescense (IF), but confirmed by electron microscopy (EM) afterwards. Immuno-electron microscopy (IEM) were applied for amyloidosis typing.

RESULTSMost patients of early renal AL were in the middle to old age. Nephrotic syndrome was the most prominent symptoms and signs accompanying with rare microscopic hematuria and hypertension. Most of them had a normal renal function. Pathological examinations of renal biopsies using LM and IF showed mild mesangial proliferation and mild thickening of glomerular basement membrane (GBM). Immunoglobulins and complements were negative or only scanty in certain cases, but in all cases there was a light chain protein deposition homogeously. There were 4 cases of minimal change glomerulopathy, 5 cases of mild mesangial proliferative glomerulonephritis, 5 cases of stage I membranous nephropathy, and 1 case of cast nephropathy diagnosed with LM. The amyloid fibrils (diameter 8 - 10 nm) were randomly distributed in the mesangium, along GBM and at the arteriolar wall under EM. Additionally, Congo red staining was positive. IEM demonstrated that amyloid fibrils labeled with colloid gold was combined with a kind of light chain protein which was confirmed as the light chain type of AL.

CONCLUSIONSThe diagnosis of early renal AL was occasionally neglected by depending only findings of LM and LF. However, special amyloid fibrils can be detected using EM. EM observation is an indispensable technique for the diagnosis of early renal AL and the typing of AL may further be determined by using IEM.

Adult ; Aged ; Amyloidosis ; metabolism ; pathology ; Basement Membrane ; metabolism ; Female ; Humans ; Immunoglobulin Light Chains ; metabolism ; Kidney Diseases ; metabolism ; pathology ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Microscopy, Immunoelectron ; Middle Aged

OBJECTIVES: The thickening of the glomerular basement membrane in rats after Vacor ingestion was examined by electron microscopy. This study was performed to elucidate which biochemical components changed in the glomerular basement membrane after Vacor-induced diabetic glomerulopathy. METHODS: Immunohistochemical analyses of type IV collagen, laminin, fibronectin and chondroitin sulfate proteoglycan were performed. A single dose of Vacor (molecular weight 272), 80 mg/kg, was administered to adult male Wistar rats by orogastric canule, and the animals were sacrificed at 0.5, 1, 3, 7, 14, 28 and 56 days after administration. RESULTS: Mild thickening of the glomerular basement membrane was evident 7 days after Vacor administration, and the width of the glomerular basement membrane was more than twice that of normal controls at 28 and 56 days. Significantly increased expressions of type IV collagen, laminin, fibronectin and neutral polysaccharide in the thickened glomerular basement membrane were noted 14 to 56 days after administration, and a mildly increased expression of chondroitin sulfate proteoglycan appeared between 3 to 7 days. CONCLUSION: These abnormally increased glomerular basement membrane components might be part of what causes diabetic nephropathy after Vacor administration.
Animal ; Basement Membrane/pathology ; Basement Membrane/metabolism ; Basement Membrane/drug effects ; Diabetic Nephropathies/pathology ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/chemically induced* ; Extracellular Matrix Proteins/metabolism ; Kidney Glomerulus/pathology ; Kidney Glomerulus/metabolism ; Kidney Glomerulus/drug effects ; Male ; Phenylurea Compounds/toxicity* ; Proteochondroitin Sulfates/metabolism ; Rats ; Rats, Wistar

Aged ; Diagnosis, Differential ; Fibronectins ; metabolism ; Glomerulonephritis, Membranoproliferative ; pathology ; Humans ; Immunohistochemistry ; Kidney Diseases ; metabolism ; pathology ; Kidney Glomerulus ; metabolism ; pathology ; ultrastructure ; Male ; Microscopy, Electron

Objective: To assess the correlation of glomerular C1q or IgA deposition with clinical and pathological features of primary membranous nephropathy (PMN) in children. Methods: The clinical and pathological manifestations including (phospholipase A2 receptor, PLA2R) and IgG subclasses staining in renal biopsies, serum anti-PLA2R antibody and therapeutic response of 33 children diagnosed with PMN in Peking University First Hospital from December 2012 to December 2020 were retrospectively summarized and analyzed. According to results of PLA2R test and findings renal pathological, the patients were divided into PLA2R-related group and non-PLA2R-related group, typical MN group and atypical MN group, C1q deposit group and non-C1q deposit group, as well as IgA deposit group and non-IgA deposit group respectively. T-test, Mann-Whitney U test and Fisher's exact probability test were used for comparison between the groups. Results: Among the 33 children with PMN, there were 20 males and 13 females, of that the age of onset was 11 (8, 13) years, and 32 patients had nephrotic level proteinuria. Renal biopsies were performed at 4.6 (2.1, 11.6) months after onset, and 28 patients (85%) received glucocorticoid or immunosuppressive therapy prior to renal biopsy. There were 20 cases (61%) with PLA2R-related MN and 13 cases (39%) with non-PLA2R-related MN. Compared with the non-PLA2R-related group, the PLA2R-related group had an older age of onset (12 (10, 13) vs. 7 (3, 12) years, Z=-2.52, P=0.011), a lower preceding infection rate (45% (9/20) vs. 11/13, P=0.032) and lower spontaneous remission rate (0 vs. 4/13, P=0.017). Renal PLA2R positivity was significantly associated with predominant or co-deposition of IgG4 (13/17 vs. 5/15, P=0.031) and low albumin levels at renal biopsy ((25±6) vs. (29±7) g/L, t=2.14, P=0.041). There were 12 patients with typical PMN and 21 patients with atypical PMN, and no significant difference in clinical and pathological manifestations was found between these 2 groups (all P>0.05). There were 10 cases (32.3%) with glomerular C1q deposition, and their disease course before renal biopsy was significantly shorter than those without C1q deposition (1.8 (0.8, 5.9) vs. 6.0 (2.5, 22.3) months, Z=-2.27, P=0.023). Twelve cases (36.4%) had glomerular IgA deposition, and their course of disease,clinical and pathological manifestations were not significantly different from those without IgA deposition (all P>0.05). Conclusion: Glomerular C1q or IgA deposition may not affect the clinical manifestations, glomerular PLA2R and IgG subclasses staining pattern, or the response to treatment of PMN in children.
Autoantibodies ; Child ; Complement C1q/metabolism* ; Female ; Glomerulonephritis, Membranous/drug therapy* ; Humans ; Immunoglobulin A/immunology* ; Immunoglobulin G ; Kidney Glomerulus ; Male ; Retrospective Studies

Animals ; Antigens, CD34 ; metabolism ; Cell Culture Techniques ; methods ; Cells, Cultured ; Endothelial Cells ; cytology ; metabolism ; Female ; Kidney Glomerulus ; cytology ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Vimentin ; metabolism

OBJECTIVETo identify potential mutation of apolipoprotein E (apoE) gene in a male patient affected with lipoprotein glomerulopathy (LPG), his mother and his sister.

METHODSThe patient and his mother both had histologically confirmed LPG. His sister and his father were asymptomatic. Genomic DNA was extracted from peripheral blood samples. PCR products of the coding region of exons 3 and 4 of the apoE gene were cloned into a pTA2 vector and sequenced. Genetic variations of the apoE gene were detected using PCR and restriction fragment length polymorphism (RFLP).

RESULTSAn apoE gene mutation was identified in the patient's family. Sequence analysis confirmed a 9-bp deletion in the exon 4 of apoE gene from nt 484 to 492. The 9-bp deletion resulted in loss of 3 amino acids at positions 143-145. The sister of the propositus carried the same mutation, though she had neither proteinuria nor elevated plasma apoE. Sequence analysis of exon 3 showed no abnormality. No abnormalities were found in the father's apoE gene sequence. Analysis of genetic variations of the apoE gene by PCR and RFLP confirmed a 57 bp fragment consistent with the 9-bp deletion in exon 4. The father had a normal ε 3 ε 3 genotype.

CONCLUSIONThe 9 bp deletion of apoE may be associated with the pathogenesis of LPG.

Adolescent ; Apolipoproteins E ; blood ; genetics ; Exons ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Kidney Diseases ; blood ; genetics ; Kidney Glomerulus ; metabolism ; pathology ; Lipoproteins ; blood ; Male ; Mutation ; Pedigree