Acute poststreptococcal glomerulonephritis superimposed on IgA nephropathy

Superimposition of poststreptococcal glomerulonephritis (PSGN) on the course of IgA nephropathy (IgAN) is uncommon. A case of PSGN during IgA nephropathy is presented. A 30-year-old man who had alternating gross and microscopic hematuria for 7 months underwent a renal biopsy. The first renal biopsy revealed IgAN with mesangial deposits of IgA and C3. Two months later, the patient suffered generalized edema, proteinuria, hematuria, an increased ASO titer and a decreased C3 level. A second renal biopsy revealed diffuse endocapillary proliferative glomerulonephritis with epimembranous hump-like electron-dense deposits of C3, but the original mesangial IgA deposits had disappeared. A diagnosis of acute PSGN was indicated. Two months after the onset of acute nephritic syndrome, the patient remained asymptomatic, except for microscopic hematuria and proteinuria. Some cases with persistent proteinuria or hematuria after PSGN are probably related to preexisting IgAN.     

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed hump electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.     

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.     

Acute endocapillary proliferative glomerulonephritis associated with human parvovirus B19 infection

A 36-year-old female developed acute nephritic syndrome associated with human parvovirus B19 (HPVB19) infection. Laboratory data showed proteinuria, hypocomplementemia, mild pancytopenia, the presence of immunoglobulin (Ig) M and IgG antibodies to HPVB 19 and positive reaction of serum HPVB19 DNA using a polymerase chain reaction (PCR). A renal biopsy showed endocapillary hypercellularity mainly of mononuclear cells with segmental apparent mesangiolytic change; fine granular IgM, IgG and C3 deposits were noted by immunofluorescence microscopy; relatively small electron-dense deposits were observed in the widened subendothelial spaces and the mesangium, and loosening of the mesangial matrix varied from place to place electron microscopically. PCR of HPVB19 DNA in the renal biopsy tissue was positive as well as in the peripheral blood. The histological findings suggested that immune-complex-mediated endocapillary proliferative glomerulonephritis is caused by acute HPVB 19 infection. We discuss the differences from poststreptococcal glomerulonephritis and the possible pathogenesis of acute endocapillary proliferative glomerulonephritis associated with HPVB19 infection.     

Strong association between IgA nephropathy and hepatitis B surface antigenemia in endemic areas

The frequency of hepatitis B surface antigen (HBsAg) was studied in the sera of 122 patients with primary IgA nephropathy. Hepatitis B surface (HBs) antigenemia was detected in 21 patients (17.2%) and this was significantly higher than the prevalence of HBsAg carrier in the general population (p less than 0.01). These patients had no clinical or laboratory findings to suggest acute or chronic liver diseases. Two glomerulopathic entities: mesangial proliferative glomerulonephritis with predominant mesangial IgA deposits and a mixed picture of membranous nephropathy with capillary IgG deposits and mesangial proliferative glomerulonephritis with mesangial IgA deposits, were observed in this group of patients. Glomerular deposits of HBsAg, hepatitis B core antigen (HBcAg), and both HBsAg and HBcAg were detected in three, five and four renal biopsy specimens respectively. Replication of hepatitis B virus (HBV) was suggested in two of the six renal biopsy specimens examined by HBV DNA gene probe. During the mean study period of 40 months (range 12-84), 19% of these patients with hepatitis B virus-associated IgA nephropathy developed progressive renal deterioration and one required maintenance dialysis therapy. Our study suggests that hepatitis B virus antigenemia may play a significant pathogenetic role in the development of IgA nephropathy in areas of high HBV endemicity and these HBV-associated IgA nephropathies can run an indolent but relentless slowly progressive clinical course.     

Dense intramembranous deposit disease: new pathologic features

The pathologic and clinical features of 16 patients with dense intramembranous deposit disease are described. By light microscopy nine patients had membranoproliferative glomerulonephritis, five had focal segmental necrotizing glomerulonephritis with segmental epithelial crescents, four of whom also had a prominent tubulointerstitial nephritis, and two had focal segmental mesangial proliferative glomerulonephritis. The patients with membranoproliferative glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis had easily recognizable dense intramembranous deposits by optical microscopy. The patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis did not have recognizable peripheral loop dense intramembranous deposits even under oil immersion. In patients with membranoproliferative glomerulonephritis ultrastructural examination revealed extensive capillary wall dense intramembranous deposits. Immunofluorescence revealed diffuse double linear staining along the capillary walls and "mesangial rings" of C3. In the patients with focal segmental necrotizing glomerulonephritis and one with focal segmental mesangial proliferative glomerulonephritis the immunofluorescence study suggested a diagnosis of dense intramembranous deposit disease because of the segmental double linear staining of the capillary walls and "mesangial rings" of C3, but the diagnosis was only established by fine structural analysis where occasional peripheral loop and prominent paramesangial basement membrane dense intramembranous deposits and mesangial nodular deposits were identified. Clinical features prior to biopsy included nephrotic syndrome in eight patients, an acute nephritic syndrome in six patients, and asymptomatic proteinuria and hematuria in two patients. Five of six patients with an acute nephritic presentation had focal segmental necrotizing glomerulonephritis. The acute renal insufficiency in these patients was transitory and appeared to be related to a prominent acute tubulointerstitial nephritis present in four of the biopsy specimens. Depressed serum C3 levels were present in patients with membranoproliferative glomerulonephritis; patients with focal segmental lesions were normocomplementemic. Because of the "atypical" light microscopic features in six of our patients, we support the suggestion that membranoproliferative glomerulonephritis, type II be replaced by the term 'dense intramembranous deposit disease' for this glomerulopathy with variable clinical and histologic features.     

Postinfectious diffuse proliferative glomerulonephritis and acute renal failure in an HIV patient

Postinfectious proliferative glomerulonephritis may occur in HIV-infected patients, although it is not a common cause of severe acute renal failure in them. We report a woman with HIV infection, who developed hypocomplementemic acute nephritic syndrome 10 days after an upper respiratory infection. Systemic diseases were excluded. The serum creatinine level increased to 6.6 mg/dl. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis, with mesangial and capillary walls, granular deposits of IgG and C3 by immunofluorescence. She was given corticosteroids with progressive normalization of her renal function. No opportunistic infections have occurred during 1-year follow-up.     

银屑病合并IgA或非IgA系膜增生性肾小球肾炎六例临床病理分析

目的分析银屑病合并肾损害的临床病理特点。方法回顾性分析北京协和医院1983年至2004年有肾活检结果的银屑病并肾损害患者6例，分析其临床及病理特点。结果男性2例，女性4例，平均年龄38岁。肾损害在银屑病发病后平均16年(7—30年)被发现。2例表现为无症状性镜下血尿和蛋白尿；3例表现为慢性肾炎综合征；1例为肾病综合征。6例均有中大量镜下血尿，其中2例有发作性肉眼血尿：蛋白尿平均为2．05g／24h(0．01—5．42g／24h)；血压4例正常，2例升高；Scr均正常。肾组织免疫荧光检查发现系膜区IgA沉积4例，系膜区IgG沉积1例，免疫荧光阴性1例。光镜表现均不严重，轻度系膜增生3例，中度系膜增生3例；均无新月体形成；慢性肾小管间质病变不明显；2例肾内动脉内膜增生、管腔狭窄。结论在银屑病合并肾损害中，系膜增生性。肾小球肾炎并不少见。可能与银屑病存在一定关系。     

Predominant synthesis of IgA with lambda light chain in IgA nephropathy

The nature of the light chains in mesangial IgA deposits and serum IgA was studied in patients with IgA nephropathy. Immunofluorescence (IF) studies using murine monoclonal antibodies, rabbit and goat anti-human monospecific antisera were performed in kidney sections from 15 IgA nephritic patients with only IgA isotype detected in the renal biopsy. Lambda light chain IF was demonstrated in all biopsy specimens and kappa light chain IF in 11 renal biopsy specimens. The majority of renal biopsies showed a predominance of lambda light chain IF staining in the mesangial deposits. The concentration of individual immunoglobulins and their light chain fractions, and the kappa/lambda ratio were determined in the serum and the supernate from peripheral blood mononuclear cells culture of 30 IgA nephritic patients and 30 age-matched healthy controls. The IgA nephritic patients had a higher serum concentration of total IgA (P less than 0.001) and a significantly lower IgA kappa/lambda ratio (P less than 0.001) compared with the controls. The kappa/lambda ratio of supernatant IgA from IgA nephritic patients (N = 20) was also significantly lower than that of the normal subjects (N = 14), both in the unstimulated (P less than 0.01) and pokeweed mitogen stimulated, peripheral blood mononuclear-cell culture (P less than 0.05). Our results showed that patients with primary IgA nephropathy displayed a unique immunologic response characterized by a predominance of IgA with lambda light chain in circulation.     

IgA nephropathy occurring in the context of previous acute glomerulonephritis

A 37-year-old female presented with acute onset of glomerulonephritis 10 days following an upper respiratory infection. Serum complement components were depressed and proteinuria exceeded 3.0 g daily. Renal biopsy revealed granular staining of IgG and C3 along the basement membrane as well as small amounts of IgA in a linear pattern. Gradual resolution of symptoms was followed by recrudescent proteinuria 2 years later. Renal biopsy at this time revealed large deposits of IgA in a mesangial staining pattern consistent with a diagnosis of IgA nephropathy. Possible mechanisms for this unusual morphologic transformation include enhanced mesangial permeability as well as mesangial sequestration of an exogenous antigen.     

Spontaneous remission of nephrotic syndrome in a patient with IgA nephropathy

A patient with spontaneous remission of nephrotic syndrome (NS) associated with IgA nephropathy is described. The patient presented at the age of 8 years with asymptomatic proteinuria, and at the age of 11 years developed classical features of NS. A percutaneous renal biopsy showed mild mesangial prominence without significant hypercellularity, electron-dense deposits within the mesangium, and 3+mesangial staining with IgA and IgG. NS resolved 6 weeks after onset without any form of therapy; absence of protein-uria persisted 6 months later. This report demonstrates clearly that patients with NS associated with IgA nephropathy may undergo spontaneous resolution of their proteinuria.     

A case of dense deposit disease associated with a group A streptococcal infection without the involvement of C3NeF or complement factor H deficiency

A 14-year-old girl presented with acute glomerulonephritis. Tests revealed hypocomplementemia and elevated Antistreptolysin-O titers, and renal biopsy revealed endocapillary and mesangial proliferative glomerulonephritis with double contours of the glomerular basement membrane (GBM). Despite methylprednisolone pulse therapy and the administration of oral prednisolone, overt proteinuria and hypocomplementemia persisted. A second renal biopsy 6 months later confirmed the initial diagnosis of dense deposit disease (DDD) based on electron-dense deposits in the GBM. C3 nephritic factor (C3NeF) and a deficiency of complement factor H (CFH) were not evident. A nephritis-associated plasmin receptor (NAPlr), nephritogenic group A streptococcal antigen, and the plasmin activity by in situ zymography were been in both the first and second biopsy specimens. The patient received combined immunomodulatory therapy with prednisolone and mizoribine, and the urinary protein decreased to a mild level at 27 months after disease onset. These findings suggest that persistent glomerular NAPlr deposition may be associated with the pathogenesis of DDD in some patients without the involvement of C3NeF or CFH mutation and that DDD patients of this type may respond to immunomodulatory treatment.     

Acute renal failure in IgA nephropathy: aggravation by gross hematuria due to anticoagulant treatment

IgA nephropathy is one of the most common forms of glomerulonephritis. Macroscopic or microscopic hematuria with mild proteinuria are the main symptoms. Without complicating factors, IgA nephropathy has a favourable long-term prognosis. We report a case of reversible acute renal failure (ARF) as a complication of mild IgA nephropathy while oral anticoagulants were administered. Diagnosis was based on a renal biopsy showing marked granular mesangial IgA-deposition. In addition, numerous tubules were extended and completely obstructed by red blood cell casts. After hemodialysis treatment and parallel anti-inflammatory steroids and after stopping anticoagulation, renal function gradually improved up to complete remission. This report indicates that anticoagulatory treatment may have negative effects on the long-term prognosis of IgA nephropathy with respect to development of ARF or tubulo-interstitial inflammation.     

Cationic dextran induces mesangioproliferative nephritis in rats independent of glomerular IgA deposition

Background. Dextran-induced mesangioproliferative glomerulonephritis in mice and, as recently reported, in rats is used as a model of IgA nephropathy. The pathogenetic role of the glomerular IgA deposits in this model, however, is unclear since IgG is often deposited in parallel. Methods. Lewis rats were immunized with cationic DEAE-dextran. Following this, rats received 5 x /week i.v. injections of 3 mg DEAE-dextran each, from days 20 to 80 and were then followed until day 120. Results. Rats developed transient proteinuria (range 63-152 mg/24 h) and haematuria on day 80. Renal biopsies obtained at days 60, 80, 100 and 120 showed mild to severe mesangioproliferative changes at days 80 and 100 which did not persist at day 120. Electron-microscopy revealed mesangial immune deposits, signs of endothelial activation and vacuoles in mesangial cells and podocytes. Compared to normal, age-matched controls, in the nephritic rats significant (P<0.05) increases were noted for glomerular total celluarity, &agr;-smooth-muscle actin expression (a marker of activated mesangial cells), monocyte/macrophage counts, and matrix proteins. Using three different antibodies, no evidence of glomerular IgA deposition was detected at any timepoint. In contrast, glomerular IgG, IgM, C3 and occasional small C5b-9 deposits were present in nephritic rats. Circulating IgG but not IgA anti-dextran antibodies could be demonstrated in nephritic rats. Conclusions. The data confirm that mesangioproliferative glomerulonephritis can be induced in rats by immunization and chronic challenge with cationic dextran. Our data also show that in rats glomerular IgG deposition rather than IgA, appears to play an important pathogenetic role in this mesangioproliferative glomerulonephritis model.     

Glomerulonephritis associated with hepatitis B surface antigenemia. Report of a case with features of both membranous and IgA nephropathy

A 40-year-old man with hepatitis B surface (HBs) antigenemia developed the nephrotic syndrome. Renal biopsy revealed a glomerulonephritis with features of both membranous glomerulonephropathy and IgA nephropathy. Histologically some glomeruli showed mesangial expansion and hypercellularity only, while others contained sclerotic segments. Direct immunofluorescence demonstrated granular IgG-bearing deposits along the peripheral glomerular capillaries and IgA-containing ones in the mesangium. HBs antigen was detected by indirect immunofluorescence both along the glomerular capillary walls and within the mesangium. Granular epimembranous and mesangial deposits were observed by electron microscopy. A few mesangial deposits consisted of spherical particles, 35-100 nm in diameter. Although 3 cases of mixed membranous and IgA nephropathy have been previously reported, this appears to be the first one to be associated with HBs antigenemia.     

De novo glomerulonephritis in patients during remission from Wegener's granulomatosis.

In a cohort of 20 consecutive patients with Wegener's granulomatosis and biopsy-proven pauci-immune crescentic glomerulonephritis three patients were in remission, but developed again a nephritic sediment without signs of systemic disease or positive ANCA titers. The second renal biopsy showed de novo mesangial IgA deposits 6, 17 and 28 months following admission for systemic disease and institution of immunosuppressive treatment. All patients were male, HLA-DR-2 positive and exhibited repeated upper respiratory tract infections. A fourth patient was admitted in end-stage renal failure with high titers of C-ANCA of the IgG isotype and proteinase 3 ab without clinical evidence of systemic manifestations of WG. Renal biopsy showed chronic sclerosing GN with marked IgA deposits. De novo development of IgA-GN is observed in a remarkable proportion of patients with WG and must be distinguished from exacerbation of the systemic disease.     

Immune-mediated glomerulonephritis after exposure to paraquat

Exposure to paraquat was followed 1 week later by mild respiratory distress in a previously healthy farmer who developed a mixed nephrotic/nephritic syndrome 3 months later. Percutaneous renal biopsy showed endo-extra-capillary proliferative glomerulonephritis associated with a linear pattern of IgG deposits along the glomerular capillary wall. This is the first case report of an association between exposure to a low dose of paraquat (as suggested by the mildness of the respiratory symptoms) and development of glomerulonephritis, possibly related to the occurrence of anti-glomerular basement membrane antibodies. The possibility is suggested that immune-mediated mechanisms of glomerular damage may be triggered by exposure to low-dose paraquat.     

Active and chronic phases of Berger's disease (IgA nephropathy)

Berger's disease, or IgA nephropathy, is generally considered as pursuing a chronic course, often with recurrent attacks of gross hematuria or persistent microscopic hematuria. However, little attention has been paid to the acute changes that may accompany this nephropathy, and there are few reports of follow-up renal biopsy studies in these patients. We have had the opportunity to study two patients with Berger's disease (IgA nephropathy) in whom initial and follow-up renal biopsy studies were available. Both of these patients presented clinically with gross hematuria and moderately heavy proteinuria. In both cases, the initial renal biopsy disclosed diffuse mesangial proliferation associated with crescent formation, while follow-up biopsy disclosed only mild mesangial proliferation and no crescents. In one case electron microscopy revealed prominent subendothelial and small mesangial deposits in the initial biopsy, which became almost solely large mesangial in the second biopsy. The other case demonstrated only mesangial deposits in both biopsies.     

Acute interstitial nephritis superimposed on glomerulonephritis: report of a case

A 7-year-old boy with a history of recurrent acute renal failure and macroscopic haematuria is reported. A renal biopsy performed during the first episode of renal function deterioration showed mesangial glomerulonephritis with C3 mesangial deposits. Macroscopic haematuria associated with respiratory infections recurred four times over the next 14 months, each time in association with acute derangement of renal function. A second biopsy showed acute interstitial nephritis and similar glomerular abnormalities. Retrospectively, a causal relationship between the ingestion of paracetamol and the appearance of the symptoms was observed. No derangement of renal function was present in subsequent episodes of macroscopic haematuria following removal of the offending drug. This is a case of drug-induced acute interstitial nephritis superimposed on a glomerular disease, and suggests the importance of recognizingthis association.     

IgA glomerulonephritis

Renal biopsy specimens from 204 patients with glomerulonephritis or nephrotic syndrome have been studied. In ten of the patients not suffering from acute poststreptococcal glomerulonephritis, systemic lupus erythematosus or Schönlein-Henoch syndrome, diffuse, selective mesangial IgA deposition was observed. Clinically, persistent microscopic haematuria, mild proteinuria and, except in one patient, normal renal function were found. Light microscopically the histological picture was dominated by a diffuse or focal increase in volume of the mesangial matrix, and mild mesangial cell proliferation. Exceptionally, there was also crescent formation. Immunofluorescence revealed large IgA, IgG and C3 deposits, as well as small IgM and fibrinogen deposits in the mesangial glomeruli. The authors' assumption that immunocomplexes containing a secretory component might be implicated in the pathomechanism of Berger's disease, could not be proved.On the basis of a lecture given at the XXIIIrd Itinerary Congress of the Transdanubian Section of the Association of Hungarian Internists, held at Gyr on 18th June, 1976. Supported by the Scientific Research Council, Ministry of Health, Hungary (3-18-0304-03-2/H).