Monocyte infiltration and cross-linked fibrin deposition in IgA nephritis and Henoch-Schoenlein purpura nephritis

To clarify the role of immune cell infiltration and fibrin deposition in glomerular injury, renal biopsy specimens taken from patients with primary IgA nephritis and Henoch-Sch?nlein purpura nephritis (HSPN) were evaluated using monoclonal antibodies specific to mononuclear cell surfaces and cross-linked fibrin (XFb). Monocytes/macrophages were the predominant cell type infiltrating glomeruli in IgA nephritis and HSPN. The intraglomerular monocyte population in both diseases was significantly higher than that in normals, mesangial proliferative (non-IgA) glomerulonephritis or minimal change nephrotic syndrome. In IgA nephritis, there was a clear correlation between glomerular monocyte accumulation and the degree of proteinuria. Although the monocyte influx tended to decline with time in HSPN, it remained unchanged in IgA nephritis. XFb deposition was found in the glomeruli of 27 out of 48 patients with IgA nephritis, and in 15 out of 20 with HSPN. The degree of XFb deposition in IgA nephritis correlated significantly with the degree of mesangial proliferation. These findings indicate a close relationship of monocyte/macrophage infiltration and XFb deposition with glomerular injury in IgA nephritis.     

Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy

BACKGROUND: Factor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated. METHODS: Twenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy. RESULTS: XFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for alpha-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium. CONCLUSION: The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.     

Soluble fibrin formation in the mesangial area of IgA nephropathy

Background Fibrin monomer and its derivatives in blood are found in an early stage of thrombosis. When they are produced in blood, they form complexes with fibrinogen, and they exist as soluble complexes named soluble fibrin (SF). As final insoluble products, cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. To clarify the mechanisms of mesangial SF production and its relationship to XFb deposition in IgA nephropathy (IgAN), an immunohistochemical study was conducted. Methods Nineteen patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure. SF was detected with a monoclonal antibody (IF-43), and factor V was detected with a specific rabbit antibody. The relationships of SF staining to the disease activity index, XFb deposition, and factor V staining was evaluated. Results XFb, factor V, and SF were observed in the mesangium in 14, 11, and 8, respectively, of a total of 19 specimens. SF had frequent staining in the proliferating areas, showing a significant relationship to XFb or factor V (P < 0.05). Furthermore, XFb, factor V, and SF depositions were markedly correlated with disease activity (P < 0.001 in each case). Conclusions These findings suggest that SF is formed in the mesangial area in active IgA nephropathy accompanied by mesangial proliferation, in particular, in its early stage.     

The role of sulfatides in autoimmunity in children with various glomerular disease]

Previous studies have suggested that autoimmunity to a number of kidney antigens may exist in glomerular disease. Our own work suggested that sulfatide which is one of the major acidic glycolipids of human kidney may be antigenic. Glycolipids were isolated from lipid extract of human kidney using thin-layer chromatography (TLC). As the major acidic glycolipids, sulfatide, CDH-sulfate, GM3, GD3 were identified. Acidic fraction of lipid extract were chromatographed and then tested for antigen by immunostaining. Sera from patients with IgA nephropathy (IgAN) and Henoch-Sch?nlein purpura nephritis (HSPN) contained antibody to the sulfatide of human kidney as determined by the direct binding of antibody to TLC. In addition, we measured the presence of sulfatide antibodies by enzyme linked immunosorbent assay (ELISA) in sera of patients with various glomerular disease: IgAN, HSPN, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), focal and segmental glomeruosclerosis (FSGS), membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), acute post streptococcal glomerulonephritis (PSAGN), and lupus nephritis (LN). IgM class sulfatide antibody were demonstrated in many cases of them. The incidence of IgA class sulfatide antibody in HSPN and IgAN was significantly high, and also the high incidence of IgG class sulfatide antibody occurred in IgAN. On the other hand, we evaluated cellular hypersensitivity to sulfatide in IgAN, HSPN, and FSGS using an active E-rosette assay. Positive results occurred in IgAN and HSPN. It was suggested that delayed hypersensitivity to sulfatide may generate an autoimmune inflammatory process. It has been reported that laminin binds specifically to sulfatide. Autoimmunity to sulfatide may disturb the laminin binding and consequently interfere with renal function. These results suggested sulfatide antigen may play important role in occurrence and aggravation of glomerular disease.     

Autoantibodies against glomerular mesangial cells and their target antigens in lupus nephritis

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Sch?enlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. OBJECTIVE: To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. METHODS: Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. RESULTS: Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. CONCLUSIONS: There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations.     

Autoantibodies Against Glomerular Mesangial Cells and Their Target Antigens in Lupus Nephritis

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Schöenlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. Objective. To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. Methods. Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. Results. Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. Conclusions. There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations.     

Serum levels of galactose-deficient IgA in children with IgA nephropathy and Henoch-Schönlein purpura

IgA nephropathy and Henoch-Schönlein purpura nephritis (HSPN) are related diseases characterized by deposits of IgA1-containing immune complexes in the renal mesangium. Adult patients with IgA nephropathy have aberrantly glycosylated IgA1 (galactose-deficient O-linked glycans) in the circulation and renal deposits. However, IgA1 glycosylation has not been studied in pediatric patients with IgA nephropathy. Using our quantitative lectin enzyme-linked immunosorbent assay (ELISA) test, we measured serum levels of galactose-deficient IgA1 of children with IgA nephropathy and HSPN and controls. Children with IgA nephropathy and HSPN had serum levels higher than those of healthy children or renal-disease controls with C1q nephropathy. Furthermore, lectin ELISA identified patients with HSPN whose clinical course mimicked that of IgA nephropathy. In summary, pediatric patients with IgA nephropathy and HSPN have an aberrancy in the glycosylation in IgA1 O-linked glycans that is similar to that in adults with IgA nephropathy.     

Detection of glomerular deposits of various renal diseases on light microscopy using periodic acid thionin [PATS]-chromotrope staining]

We devised a periodic acid thionine schiff (PATS)-chromotrope method to detect the glomerular deposits more distinctly than conventional staining methods. The PATS-chromotrope method was compared with other immunological staining methods, such as immunofluorescence method and avidin biotin complex method. Formalin-fixed, and paraffin-embedded renal tissues were obtained from 26 patients with IgA nephropathy, 8 with lupus nephritis, 4 with minimal change nephrotic syndrome, 3 with membrano-proliferative glomerulonephritis, and 3 with hepatitis-B associated nephropathy. Thionine Schiff reagent was used instead of fuchsin-schiff reagent to stain the basement membrane blue. Subsequently, chromotrope 2R was used to stain the glomerular deposits. For immunofluorescence method, frozen renal tissues were stained with FITC-labelled anti-human IgG, IgA, C3 and fibrinogen. For avidin biotin complex method, the same sections as PATS-chromotrope method were stained with anti-human IgG, IgA, and C3. In PATS-chromotrope method, deposits were identified in 9 of 26 specimens with IgA nephropathy, 3 of 8 specimens with lupus nephritis, and one of 3 specimens with hepatitis-B associated nephropathy. Localization of deposits in PATS-chromotrope method was identified more distinctly than immunofluorescence method or avidin biotin complex method. PATS-chromotrope method is useful to detect the deposition of immune complex on routine light microscopy in human glomerular disease.     

Cellular and non-cellular compositions of crescents in human glomerulonephritis

The composition of glomerular crescents was examined on the frozen kidney sections obtained from 10 patients (5 patients with IgA nephropathy, two with Henoch-Sch?nlein purpura nephritis and three with glomerulonephritis due to undetermined etiology) using well-defined monoclonal and polyclonal antibodies to coagulation proteins, extracellular matrices, intermediate filament proteins and immune cells. Fibrinogen/fibrin related antigens (FRA), which were stained with anti-fibrinogen serum, were positive in the crescents of all the patients, but monoclonal antibody to crosslinked fibrin or von Willebrand factor (factor VIII related) antigen did not bind to the crescents. This suggests that the FRA deposited in the crescents is fibrinogen or its degradation products rather than fibrin. Staining for intrinsic components of renal basement membrane, including type IV and V collagens, laminin and fibronectin, were consistently positive in all stages of the crescents. Cytokeratin, showing cytoplasmic staining of the glomerular parietal epithelium and tubular epithelium in the normal kidney, was demonstrated in three patients with cellular crescents. Vimentin, which is normally distributed in parietal and visceral epithelial cells in the glomeruli and interstitial cells, was found at all stages of the crescents. These findings suggest that in the early stage of crescent formation, glomerular epithelial cells play an important role, and that the accumulation of intrinsic basement membrane constituents is associated with the formation and progression of the crescents. None of the crescent cells reacted with either of two monoclonal antibodies (Mo2 and FMC 32) to monocytes/macrophages or with nonspecific esterase staining. It seems that, at least in our patients, monocytes are a minor factor contributing to the formation of glomerular crescents.     

Significance of urinary binucleated podocytes in IgA nephropathy

Background: We have reported clinico-pathological significance of podocytes excreted in urine in previous papers. During these studies we found the presence of binucleated podocytes in urine. The aim of the present study was to look for the significance of urinary binucleated podocytes in IgA nephropathy.
Patients and methods: 123 patients aged 2–25-year-old with various renal diseases were studied: UTI, five cases; nephrotic syndrome, 30 cases; MGN, three cases; MPGN, six cases; Alport syndrome, five cases; lupus nephritis, seven cases; HSPN, 12 cases; IgA GN, 50 cases. A total of 1225 urine samples from these diseases were examined. As a control, 203 urine samples from 100 normal healthy children were examined.
Usual IF using monoclonal antibody to podocalyxin was used to detect urinary podocytes and binucleated podocytes.
The presence of urinary binucleated podocytes were confirmed by immunoelectron microscopic examination and confocal immunofluorescent examination.
Pathological changes were scored into six items: acute intracapillary, chronic intracapillary, acute extracapillary, chronic extracapillary, acute tubulo-interstitial and chronic tubulo-interstitial lesions.
Results:

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  Urinary binucleated podocytes were found in various renal disases.

       
  
  

Role of β2 integrins in glomerular leucocytes in Henoch-Schoenlein purpura nephritis: an age-matched comparative study with immunoglobulin A nephropathy

SUMMARY: A comparative immunohistological study was performed for the glomerular deposition of complements (C1q and C3c), fibrin/fibrinogen‐related antigen (FRA), the expression of intercellular adhesion molecule‐1 (ICAM‐1), and the infiltration of leucocytes bearing β₂ integrins (leucocyte function associated antigen‐1 (LFA‐1), complement receptor 3 (CR3) and complement receptor 4 (CR4)) on renal biopsy specimens from 49 cases with Henoch‐Schoenlein purpura nephritis (HSPN), and 49 age‐matched cases with immunoglobulin A nephropathy (IgAN). the glomerular expression of ICAM‐1 was signifcantly correlated with the glomerular infiltration of leucocyte function associated antigen (LFA)‐1⁺ leucocytes in both diseases, and with that of CR3⁺ leucocytes in HSPN. the expression of ICAM‐1 was closely localized with the infiltration of LFA‐1⁺ leucocytes in the study with double immunostaining. the incidence and intensity of glomerular deposition of FRA were significantly higher in HSPN than in IgAN (P< 0.001), and those of C3c were significantly lower in HSPN than in IgAN (P< 0.001). the glomerular deposition of FRA was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in HSPN (P<0.05) but not in IgAN. In contrast, the glomerular deposition of C3c was significantly correlated with the glomerular infiltration of CR4⁺ leucocytes in IgAN (P<0.05), but not in HSPN. Studies with double immunostaining revealed a close association of CR4⁺ leucocytes with FRA deposition in HSPN and with C3c deposition in IgAN, respectively. the number of glomerular leucocytes bearing β₂ integrins was significantly correlated with urinary protein at the time of renal biopsy in both diseases. These results suggested the differential roles of β₂ integrins in the induction of glomerular injury in HSPN and IgAN. the ICAM‐1/LFA‐1 interaction may commonly be involved in the glomerular infiltration of leucocytes in both diseases. the ICAM‐1/CR3 interaction may be involved only in HSPN. Complement receptor 4 may function as a fibrin/fibrinogen receptor in HSPN, while CR4 may function as a complement receptor in IgAN.     

Intraglomerular monocytes in human glomerulonephritis.

A total of 246 cases of 166 primary glomerulonephritis (GN) and 80 secondary GN were examined for the presence of intraglomerular monocytes using nonspecific esterase reaction of alpha-naphthyl butyrate methods. The high score of monocyte index (MI) as the numbers of monocytes per glomerulus was found in crescentic GN (n = 5, MI = 3.72 +/- 1.98), endocapillary proliferative GN (n = 8, MI = 2.17 +/- 2.13), lupus nephritis (n = 43, MI = 2.21 +/- 3.35), and cryoglobulinemia-related GN (n = 1, MI = 11.5). The intermediate score of MI was observed in IgA nephropathy (IgA-N, n = 64, MI = 0.63 +/- 0.42) and Henoch-Sch?nlein purpura nephritis (HSP-N, n = 11, MI = 1.09 +/- 0.87). Out of IgA-N and HSP-N, the scores of MI in patients with more severe proliferation and/or with segmental lesions were higher than those without this histological finding. However, there was not a significant correlation between the glomerular monocytic infiltration and clinical findings in each group. In primary GN including minor glomerular abnormalities, focal glomerular sclerosis and membranous GN, and in secondary renal diseases except for SLE, HSP, and cryoglobulinemia, the score of intraglomerular monocytic infiltration was of little value. The participation of monocytes was predominant in extra- and intracapillary GN, lupus nephritis, and cryoglobulinemia-related GN, as previously reported. Moreover, in some types of proliferative GN, especially IgA-N and HSP-N, some parts of glomerular hypercellularity result from the participation of monocyte-macrophage series, although the main parts of cell proliferation are intrinsic mesangial cells.     

Primary antiphospholipid antibody syndrome and mesangial IgA glomerulonephritis

The antiphospholipid antibody syndrome (APS) is characterized by recurrent thrombosis, fetal loss, multiorgan involvement, and the presence of lupus anticoagulant and/or anticardiolipin antibody. When not associated with systemic lupus erythematosus, other collagen diseases, or ingestion of medications, the condition is called primary APS. The kidney may be involved in the APS syndrome with acute nephritis and renal failure. The cases with renal biopsy studies have shown variable glomerular morphology, ranging from mild mesangial changes to a diffuse endocapillary proliferative glomerulonephritis. The most frequent lesion is thrombotic microangiopathy or features seen in the hemolytic uremic syndrome. Apart from fibrin thrombus deposition, only a few cases have shown focal and segmental deposits of IgG and/or IgM and/or C3. We describe a patient with primary APS who had thrombosis with lower limb amputation and acute renal failure. The renal biopsy specimen showed a focal proliferative glomerulonephritis with endothelial proliferation and damage, with diffuse heavy mesangial deposits of IgA and fibrinogen. This case with diabetes mellitus, but without diabetic nephropathy, represents the occurrence of primary APS and mesangial IgA nephropathy which potentiated the renal injury, leading to acute renal failure. The relationship to the Henoch-Sch?nlein syndrome is discussed.     

Portions of basement membrane with decreased negative charge in various glomerulonephritis

The decrease in negative charge was evaluated in different portions of the basement membrane as well as the lamina rara externa (LRE) and lamina rara interna (LRI). The subjects were nine patients [2 patients with focal segmental glomerulosclerosis (FGS), 2 with membranoproliferative glomerulonephritis (MPGN), 3 with IgA nephropathy, and 2 with Henoch-Schoenlein purpura nephritis (HSPN)] and 2 patients with minor glomerular abnormalities and 1 with tubulo-interstitial nephritis (TIN) as controls. Polyethyleneimine (PEI) was used as a cationic probe. The basement membrane was divided into the peripheral portion (loop basement membrane 7 microns or more from the anchor portion), proximal portion (within 3 microns of the anchor portion), and the paramesangial portion in the paramesangial basement membrane. In each portion, PEI granules per 1 micron of the LRE and LRI were counted. Anionic sites were decreased in the patients with FGS and MPGN, but the damage pattern differed between the two diseases. In the patients with FGS, the decrease in anionic sites was most marked in the peripheral portion with an even greater decrease in the LRI. In the patients with MPGN, the decrease was uniform among the portions. On the other hand, no significant difference was observed in any portion between the patients with IgA nephropathy or HSPN and the controls. The portions with decreased negative charge varied among various glomerular diseases, suggesting different developmental mechanisms.     

Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry

BackgroundGlomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry.Materials and MethodsWe investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry.ResultsOf the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors.ConclusionsExamination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN.     

Histology and immunohistology of IgA nephropathy

IgA nephropathy is a histologically diverse glomerular disease characterized by mesangial or mesangial plus peripheral glomerular capillary immune complex deposits that contain IgA as the dominant or co-dominant immunoglobulin type. The most common histologic manifestation of IgA nephropathy is mesangial proliferative glomerulonephritis (GN), most often focal but not infrequently diffuse. However, the light microscopic appearance of IgA nephropathy spans the entire range from histologically normal to diffuse proliferative and crescentic glomerulonephritis, much as is the case with lupus nephritis. This review examines the histologic diversity as well as the immunohistologic features of IgA nephropathy.     

Henoch-Schoenlein nephritis and IgA nephropathy in children: a comparison of clinical course

The clinical presentation, initial laboratory and renal biopsy findings, and subsequent clinical course were studied and compared in 128 children with Henoch-Schoenlein (HS) nephritis and in 206 children with IgA nephropathy. The clinical and pathological findings of the two conditions were similar. After a mean follow-up period of 5 years, 72 patients (56%) with HS nephritis and 67 (32%) with IgA nephropathy showed no demonstrable abnormality, 29 (23%) with HS nephritis and 103 (50%) with IgA nephropathy had minor urinary abnormalities, 7 (5%) with HS nephritis and 26 (13%) with IgA nephropathy had heavy proteinuria and/or hypertension, and 20 (16%) with HS nephritis and 10 (5%) with IgA nephropathy had developed chronic renal failure. A worse outcome was significantly associated with the more severe clinical presentations and more severe glomerular changes by light microscopy in HS nephritis, whereas there was no relationship between the severity of clinical presentation and glomerular changes and prognosis in IgA nephropathy. These findings suggest that HS nephritis is an acute disease and prognosis is associated with the severity of glomerular changes at onset, while IgA nephropathy is a chronic, slowly progressive glomerular disease.     

Clinicopathological features of antineutrophil cytoplasmic antibodies associated vasculitis with glomerular IgA deposits

Objective To investigate the clinical manifestations, renal pathology and prognosis of antineutrophil cytoplasmic antibody-associated small-vessel vasculitis (AAV) accompanied with renal glomerular IgA deposition. Methods A retrospective analysis was performed at the First Affiliated Hospital of Zhejiang University College of Medicine. Patients diagnosed with AAV associated renal injury by renal biopsy from February 2004 to February 2017 were enrolled. Patients with antiglomerular basement membrane antibody-mediated nephritis, systemic lupus erythematosus nephritis, Henoch Schonlein purpura nephritis, hepatitis B virus associated nephritis and other known etiology were excluded. According to immunofluorescence examination, the patients were divided into IgA deposition group and pauci-immune complex deposition group. The differences in clinical manifestation, pathological features and prognosis were compared between groups. Results A total of 150 AAV cases were included, among which 25 cases were with IgA deposition and 125 cases with pauci-immune complex deposition. The level of serum albumin in IgA deposition group was higher than that in pauci-immune complex deposition group [(35.0±6.2) g/L vs (32.6±5.3) g/L, P=0.049], but the titer of MPO-ANCA was lower [24.8(10.4, 71.8) U/ml vs 63.0(21.9, 100.0) U/ml, P=0.044] in IgA deposition group. There was no significant difference between two groups in other laboratory indexes and renal pathological findings. The median follow-up time was 15.2 months in IgA deposition group and 8.9 months in pauci immune complex deposition group. During the follow-up there were 8 patients (32.0%) in IgA deposition group and 29 patients (23.2%) in pauci immune complex deposition group on maintaining dialysis; 2 patients (8.0%) in IgA deposition group and 7 patients (5.6%) in pauci immune complex deposition group died. There was no significant difference between two groups in patients' outcomes. Conclusions AAV patients with glomerular IgA deposition and AAV patients with typical glomerular immunoglobulin complex deposition are similar as regards clinical appearance and prognosis.     

Glomerular T cell and monocyte populations in patients with IgA nephropathy

Renal tissues from 19 patients with the minimal or slight stage of IgA nephropathy were examined for evidence of glomerular T cell or monocyte infiltration using monoclonal antibodies to identify T cells (OKT3, OKT11), T cell subsets (OKT4, OKT8), and monocytes and null cells (OKM1) by indirect immunofluorescence. Renal tissues from 12 patients at the same stage of mesangial proliferative glomerulonephritis without IgA deposition were also investigated by these procedures. Light microscopic examination of the same renal tissues was also performed. Reactive glomerular mononuclear cells were found to be numerous in patients with IgA nephropathy. The most prominent type of glomerular cells was OKT8 positive. T cell subsets and OKM1 positive cells in glomeruli from patients with IgA nephropathy were significantly increased as compared to those from patients with mesangial proliferative glomerulonephritis. Focal segmental proliferation of mesangial cells was observed in glomeruli which showed an accumulation of OKT8 positive cells. It is concluded that the immuno-regulatory mechanism involving T cells and/or monocytes might be one of the exacerbating factors in patients with IgA nephropathy.     

The spectrum of children's kidney diseases—9925 renal biopsy-proven cases from a single center of China between 2004 and 2017

Objective To analyze the spectrum of children's kidney pathology by renal biopsy. Methods The clinical and pathological data of the cases in Jinling Hospital involving the patients younger than 18 years old who received renal biopsy from April 1st, 2004 to December 31th, 2017 were retrospectively collected, and compared with the renal pathological data of 1611 children aged 0-18 years from June 1982 to March 2004. Results This study included 9925 cases of kidney diseases proven by renal biopsy. The ratio of male to female was 1.79∶1. Primary glomerulonephritis (PGN) accounted for 66.14%, and secondary glomerulonephritis (SGN) accounted for 28.00%. Top five of the PGN were IgA nephropathy (IgAN, 19.11%), mesangial proliferative glomerulonephritis (MsPGN, 16.07%), minimal change disease (MCD, 14.20%), focal segmental glomerulosclerosis (FSGS, 6.19%) and membranous nephropathy (MN, 4.70%) in whole children, IgAN (13.12%), MsPGN (11.20%), MCD(10.63%), FSGS (4.55%) and MN (2.54%) in males, and IgAN (5.99%), MsPGN (4.87%), MCD (3.57%), MN (2.16%) and FSGS (1.63%) in females. Top three of the SGN were Henoch-Schonlein purpura nephritis (HSPN, 17.74%), lupus nephritis (LN, 8.23%) and vasculitis nephropathy (1.82%). The male was in a dominant position in all kinds of pathologic types than female except LN. HSPN was the most frequent type in adolescents between 6-13 years old. LN was the commonest one in 14-18-year-old girls, while IgAN was the the most common in 14-18-year-old boys. Post infective nephritis was the most popular in 12-14-year-old teenagers. It was also found that MN ascended in female. When compared with the data before 2004, HSPN and LN accounted for a greater proportion in SGN, post infective nephritis displayed a smaller proportion. Conclusions PGN is the mainly kind of glomerular disease as before, and immune disorder related to glomerular diseases increase and post infective nephritis decreases in proportion. This study provides the reference and epidemic data for diagnosis, treatment and prevention of children's renal diseases.