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

OBJECTIVETo investigate the potential of renal pathological index as a differential diagnosis factor for Chinese medicine (CM) syndromes typing in IgA nephropathy (IgAN).

METHODSA total of 1,016 patients with IgAN was recruited from November 2001 to November 2004. All the signs and symptoms including picture of the tongue and pulse tracings were collected. All patients were typed according to the CM syndrome typing scheme for chronic primary glomerulopathy. The severity of glomerulus and tubulointerstitial lesions (mild, moderate-severe) were evaluated using lee's grading system and the Katafuchi score system.

RESULTSThe syndrome types transform in turn by deficiency of both the Spleen (Pi) and Lung (Fei) qi, deficiency of both qi and yin, deficiency of Liver (Gan) and Kidney (Shen) yin and deficiency of Spleen-Kidney (Shen) yang, with the aggravation of pathogenetic condition and that the manifestation of deficiency of qi clinically showed proliferative lesion of glomerular mesangium, while the glomerular sclerosis pathologically showed the manifestation of yin deficiency.

CONCLUSIONRenal pathological findings may be a candidate of objective factors to refine CM syndrome typing process.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Female ; Glomerulonephritis, IGA ; classification ; immunology ; pathology ; therapy ; Humans ; Kidney ; blood supply ; pathology ; Kidney Glomerulus ; pathology ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Renal Artery ; pathology ; Syndrome ; Young Adult

OBJECTIVETo investigate whether FTY720 inhibits rat mesangial proliferation and extracellular matrix expansion through suppression of transforming growth factor β1-connective tissue growth factor (TGFβ1-CTGF) pathway, and to explore experimental evidence for its effect on mesangial proliferative glomerulonephritis.

METHODSA rat model of anti-Thy-1 mesangial proliferative glomerulonephritis was established and FTY720 intervention was performed. Periphery blood lymphocyte count, urine protein excretion, glomerular mesangial proliferation, protein and gene expression of TGFβ1 and CTGF and extracellular matrix protein including fibronectin, laminin and collagen IV in isolated glomeruli were documented at 1, 3 and 7 days after injection of anti-Thy-1 antibody.

RESULTSThe model group developed proteinuria at 1, 3 and 7 days after injection of anti-Thy-1 antibody, which were significantly higher [(27.9 ± 7.3), (63.5 ± 18.8) and (52.4 ± 15.4)mg/d, respectively] than those in the control group [(8.4 ± 2.4), (8.4 ± 2.1) and (10.4 ± 3.2) mg/d; respectively, P < 0.01]. FTY720 intervention group showed significantly decreased proteinuria at 3 and 7 days after injection [(31.4 ± 7.0), (25.5 ± 7.7) mg/d, respectively] than model group (P < 0.01), although higher than the control group (P < 0.01). After intervention for 3 and 7 days, FTY720 significantly down-regulated both TGFβ1 and CTGF gene and protein expression in cultured glomeruli, and suppressed the production of glomerular extracellular matrix protein secretion, leading to attenuated mesangial cell proliferation and extracellular matrix expansion in rat anti-Thy-1 mesangial proliferative glomerulonephritis.

CONCLUSIONFTY720 significantly attenuates mesangial proliferation and extracellular matrix expansion through inhibition of TGFβ1-CTGF pathway in rat, and thus ameliorates the development of anti-Thy-1 mesangial proliferative glomerulonephritis.

Animals ; Cell Proliferation ; Connective Tissue Growth Factor ; genetics ; metabolism ; Down-Regulation ; Extracellular Matrix Proteins ; metabolism ; Fingolimod Hydrochloride ; Gene Expression ; Glomerular Mesangium ; metabolism ; pathology ; Glomerulonephritis, Membranoproliferative ; immunology ; metabolism ; pathology ; Immunosuppressive Agents ; pharmacology ; Isoantibodies ; immunology ; Kidney Glomerulus ; metabolism ; pathology ; Male ; Propylene Glycols ; pharmacology ; Proteinuria ; urine ; Rats ; Rats, Wistar ; Signal Transduction ; drug effects ; Sphingosine ; analogs & derivatives ; pharmacology ; Thy-1 Antigens ; immunology ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo examine inhibition action of multi-glycoside of Tripterygium wilfordii (GTW) on infiltration of inflammatory cell in glomeruli with anti-Thy1.1 glomerulonephritis (anti-Thy1.1 GN), and to clarify its effects on inflammatory in vitro.

METHODTwo types of anti-Thy1.1 GN were induced in rats by a single or two intravenous injections with 500 microg of anti-Thy1.1 mAb 1-22-3. Rats were randomly divided into two groups, the GTW group and control group, and sacrificed on day 7 or on day 42 after induction of anti-Thy1.1 GN. Daily oral administration of different dose of GTW and distilled water as a control was started from 3 days before injection or at the same time of injection till the day of sacrifice. Proteinuria was determined during days 7 or during days 42. Infiltration of macrophage and T lymphocyte in glomeruli and mRNA expression of interleukin (IL)-2 and interferon (IFN)-gamma in renal tissue were examined.

RESULTIncrease of infiltration of macrophage in reversible anti-Thy1.1 GN model, glomerular macrophage infiltration and IL-2 mRNA expansion were attenuated by higher dose of GTW (75 mg x kg(-1) x d(-1)), and increased accumulation of activated macrophage and T lymphocyte in irreversible anti-Thy1.1 GN model, accumulation of macrophage and T lymphocyte in glomeruli and mRNA expansion of IL-2 and IFN-gamma were decreased by middling dose of GTW (50 mg x kg(-1) x d(-1)) as well. Proteinuria was significantly ameliorated after GTW administration.

CONCLUSIONThe findings suggested that different dose of GTW can ameliorate infiltration of inflammatory cell in glomeruli with anti-Thy1.1 glomerulonephritis in vitro by decreasing the expression of IL-2 and IFN-gamma.

Animals ; Antibodies, Monoclonal ; immunology ; Dose-Response Relationship, Drug ; Female ; Gene Expression Regulation ; drug effects ; Glomerulonephritis ; immunology ; metabolism ; pathology ; physiopathology ; Glycosides ; pharmacology ; Inflammation ; metabolism ; pathology ; physiopathology ; Interferon-alpha ; genetics ; Interleukin-2 ; genetics ; Kidney Glomerulus ; drug effects ; pathology ; Macrophages ; drug effects ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Rats ; T-Lymphocytes ; drug effects ; metabolism ; Tripterygium ; chemistry

We report a case of light chain deposition disease in a 59-yr-old female showing deposition of monoclonal light chain in the kidney and bone marrow accompanied with a schistocytosis, the morphologic finding of microangiopathic hemolytic anemia. The immunofluorescence examination of the kidney revealed strongly stained kappa-light chain deposits on the glomerular mesangium and capillary wall, tubules, and vessel wall. The electron microscopy demonstrated electron-dense deposits on the glomerular basement membrane and mesangium. Anemia was observed with schistocytosis and Howell-Jolly body in the peripheral blood smears. The immunohistochemical examination of the bone marrow showed the presence of kappa-light chain deposits in scattered plasma cells and thickened vessel wall in the absence of a prominent plasma cell proliferation. Although an immunofixation electrophoresis failed to detect a monoclonal gammopathy, the presence of monoclonal protein could be identified by an abnormal kappa/lambda ratio on the serum free light chain analysis.
Anemia, Hemolytic/complications/*diagnosis ; Bone Marrow/*pathology ; Female ; Glomerulonephritis/complications/*diagnosis/pathology ; Humans ; Immunoglobulin Light Chains/*analysis ; Kidney Glomerulus/*pathology/ultrastructure ; Middle Aged ; Paraproteinemias/complications/*diagnosis/immunology

OBJECTIVETo study the expression and significance of nestin (a type of cytoskeletal protein) in normal and diseased human kidneys.

METHODSDiseased kidney tissues were obtained from needle biopsies in 32 patients with glomerulonephritis (including 8 cases of membranous glomerulopathy, 3 cases of focal segmental glomerulosclerosis, 17 cases of IgA nephropathy with proteinuria and 4 cases of IgA nephropathy without proteinuria). Control kidney tissues were obtained from nephrectomy specimens for renal tumors. The expression of nestin in the control kidney tissues was studied using immunoelectronic microscopy and immunohistochemistry. The expression of nestin in the diseased kidney tissues was detected by immunohistochemistry and real-time reverse transcription-polymerase chain reaction.

RESULTSIn normal kidney tissues, nestin was detected at the periphery of glomerular capillary loops. Semi-quantitative morphometric analysis showed that the glomerular nestin expression level in cases of IgA nephropathy without proteinuria did not differ from that in the normal controls. However, the glomerular nestin expression levels in cases of IgA nephropathy with proteinuria, membranous glomerulopathy and focal segmental glomerulosclerosis were significantly lower than those in the normal kidneys and IgA nephropathy without proteinuria. The glomerular nestin expression levels inversely correlated with the 24-hour urine protein results.

CONCLUSIONNestin may play an important role in maintaining the normal function of podocytes in human kidney.

Adult ; Gene Expression Regulation ; Glomerulonephritis, IGA ; immunology ; Humans ; Immunohistochemistry ; Intermediate Filament Proteins ; genetics ; metabolism ; Kidney ; Kidney Diseases ; metabolism ; pathology ; Kidney Glomerulus ; metabolism ; pathology ; Middle Aged ; Nephrectomy ; adverse effects ; Nerve Tissue Proteins ; genetics ; metabolism ; Nestin ; Proteinuria ; metabolism

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 observe the dynamic changes of dendritic cells (DCs) in the renal graft of rats within 72 h after renal transplantation.

METHODSUsing SD rats as the donors and Wistar rats as the recipients, renal transplantation was performed in 30 pairs of rats, with another 5 donor kidneys that were not transplanted serving as the sham operation group. The transplanted kidneys were harvested at 1, 6, 12, 24, 48 and 72 h after recovery of blood circulation, paraffin-embedded and sectioned ,followed by HE staining and immunohistochemical staining for S-100 protein for DC identification. The pathological changes and the DC density per glomerulus in the renal graft were observed with optical microscope.

RESULTSNo signs of acute rejection were found in these sections. Few DCs were observed in the sham operation group and in the renal graft 1 h after transplantation. The number of DCs in the renal graft increased with time and reached the maximum 24 h after transplantation followed by gradual decrease.

CONCLUSIONSWithin 72 h after renal transplantation, the number of DCs in the graft varies following a curve with a single peak. Increased DC density in the graft may result from recipient DC migration into the graft, and accordingly, decreased recipient DC migration results in decrease of DC density in the graft. The pattern of DC number variation in the graft can be helpful to further improve the therapy against graft rejection.

Animals ; Cell Count ; Cell Movement ; immunology ; Dendritic Cells ; cytology ; immunology ; Female ; Graft Rejection ; prevention & control ; Kidney Glomerulus ; immunology ; Kidney Transplantation ; immunology ; Male ; Rats ; Rats, Wistar ; Time Factors

Antibodies, Antineutrophil Cytoplasmic ; blood ; Biopsy ; Child ; Diagnosis, Differential ; Female ; Humans ; Kidney Glomerulus ; pathology ; Lupus Erythematosus, Systemic ; complications ; immunology ; Lupus Nephritis ; diagnosis ; etiology ; immunology ; pathology ; Necrosis

Animals ; Collagen Type IV ; metabolism ; Fibronectins ; metabolism ; Glomerulonephritis, Membranous ; metabolism ; pathology ; Immune Sera ; immunology ; Kidney Glomerulus ; pathology ; ultrastructure ; Male ; Malondialdehyde ; blood ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species ; pharmacology ; Superoxide Dismutase ; blood ; Taurine ; pharmacology ; Transforming Growth Factor beta1 ; metabolism