Diffuse Crescentic Glomerulonephritis Research Articles

Atypical Anti-Glomerular Basement Membrane Nephritis: A Case Series From the French Nephropathology Group

Rationale & ObjectiveAtypical anti-glomerular basement membrane (GBM) nephritis is characterized by a bright linear immunoglobulin staining along the GBM by immunofluorescence without a diffuse crescentic glomerulonephritis nor serum anti-GBM antibodies by conventional ELISA. We characterized a series of patients with atypical anti-GBM disease. Study DesignCase series. Setting & ParticipantsPatients were identified by the French Nephropathology Group as having atypical anti-GBM nephritis between 2003 and 2022. FindingsAmong 38 potential cases, 25 were included. 14 (56%) were female and 23 (92%) had hematuria. Median [interquartile range (IQR)] serum creatinine at diagnosis was 150 [102-203] μmol/L and median [IQR] urine protein to creatinine ratio was 2.4 [1.3-5.2] g/g. 9 (36%) patients had endocapillary proliferative glomerulonephritis (GN), 4 (16%) had mesangial proliferative GN, 4 (16%) had membranoproliferative GN, 2 (8%) had pure and focal crescentic GN, 1 (4%) had focal segmental glomerulosclerosis, and 5 had glomeruli that were unremarkable on histopathology. Nine patients (36%) had crescents, involving a median of 9% of glomeruli. Bright linear staining for IgG was seen in 22 cases (88%) and for IgA in 3 cases (12%). The nine patients (38%) who had a monotypic staining pattern tended to be older with less proteinuria and rarely had crescents. Kidney survival rate at one year was 83% and did not appear to be associated with the light chain restriction. LimitationsRetrospective case series with a limited number of biopsies including electron microscopy. ConclusionsCompared to typical anti-GBM disease, atypical anti-GBM nephritis frequently presents with endocapillary or mesangial proliferative glomerulonephritis pattern and appears to have slower disease progression. Further studies are needed to fully characterize its pathophysiology and associated clinical outcomes.

Bartonella endocarditis and diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition

BackgroundBartonella endocarditis is often a diagnostic challenge due to its variable clinical manifestations, especially when it is first presented with involvement of organs other than skin and lymph nodes, such as the kidney.Case presentationThis was a 13-year-old girl presenting with fever, chest and abdominal pain, acute kidney injury, nephrotic-range proteinuria and low complement levels. Her kidney biopsy showed diffuse crescentic proliferative glomerulonephritis with a full-house pattern of immune complex deposition shown by immunofluorescence, which was initially considered consistent with systemic lupus erythematous-associated glomerulonephritis (lupus nephritis). After extensive workup, Bartonella endocarditis was diagnosed. Antibiotic treatment and valvular replacement surgery were undertaken with subsequent return of kidney function to normal range.ConclusionThis case demonstrates the importance of considering the full clinical picture when interpreting clinical, laboratory and biopsy findings, because the treatment strategy for infective endocarditis versus lupus nephritis is drastically different.

Clinico-Pathological Correlations of Poststreptococcal Glomerulonephritis

Abstract Postinfectious glomerulonephritis is associated with bacterial, viral, fungal, and parasitic infectious agents and histologically appears most often as acute diffuse endocapillary or proliferative glomerulonephritis secondary infection with: group A streptococcus, streptococcus viridans, staphilococus aureus, diploccocus pneumoniae, Brucella melitensis, Salmonella typhi, Yershinia enterocolitica, Plasmodium falciparum, meningococcus, Mycoplasma, Klebsiella, varicella, variola, mumps. Less commonly, it appears as diffuse crescentic glomerulonephritis and a lot of infectious causes are incriminated like: streptococcus, legionella, varicella, Treponema pallidum or as focal crescentic glomerulonephritis: streptococcus A. It rarely appears as mesangiocapillary glomerulonephritis secondary infection with: streptococcus viridans, hepatitis C virus; diffuse or focal mesangial proliferative glomerulonephritis: hepatitis B virus, salmonella, adenovirus, influenza virus, salmonella; focal segmental, necrotizing and sclerosing glomerulonephritis: bacterial endocarditis; membranous glomerulonephritis: hepatitis B virus, syphilis, filarial, Mycobacterium, plasmodium falciparum; focal proliferative: Mycoplasma; mesangiolytic glomerulonephritis :Echo virus. Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific nephritogenic strains of group A beta-hemolytic streptococcus. The clinical presentation of PSGN varies from asymptomatic, microscopic hematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), edema, hypertension, and acute kidney injury. The prognosis is generally favorable, especially in children, but in some cases, the long-term prognosis is not benign. Managing a case of PSGN requires cooperation between internists, nephrologists, infectious disease consultants, pharmacists, and nursing staff, functioning as an interprofessional team, to provide excellent care for their patients.

Impaired HVJ-stimulated Interferon producing capacity in MPO-ANCA-associated vasculitis with rapidly progressive glomerulonephritis lead to susceptibility to infection

ANCA-associated RPGN leads to renal failure through systemic vasculitis and diffuse crescentic glomerulonephritis. MPO-ANCA-RPGN patients are highly susceptible to infections. Our aim in this study was to uncover reasons why these patients were susceptible to infections. We analyzed various aspects of type I interferon system including HVJ-stimulated IFN-α producing capacity and plasmacytoid dendritic cell (pDC) number in whole blood in MPO-ANCA-RPGN patients. Compared with healthy subjects, MPO-ANCA-RPGN patients showed impaired HVJ-stimulated IFN-α producing capacity and lower pDC number with or without glucocorticoid treatment. Immuno-histological staining of MPO-ANCA-RPGN kidney samples revealed a few but apparent pDC in T cell infiltrating regions even in patients with low pDC number in their peripheral blood. Patients’ low HVJ-stimulated IFN-α producing capacity and pDC numbers persisted even after patients underwent several years of treatment. Former infection was determined using patients’ serum BPI, Lamp-2 and Calprotectin, since they are reflective of a history of infection. These markers were higher in MPO-ANCA-RPGN patients than in healthy subjects. These results indicate that impaired HVJ-stimulated IFN-α production as well as dysfunction of the IFN system might have resulted from a previous bout of infection and can be partially implicated in patients’ long-term susceptibility and vulnerability to infection.

Atypical Anti-Glomerular Basement Membrane Disease With Diffuse Crescentic Membranoproliferative Glomerulonephritis: Case Report and Review of Literature.

Anti-glomerular basement membrane (anti-GBM) disease occurs in fewer than two cases per million population. Patients usually present with features of rapidly progressive glomerulonephritis (RPGN) with or without pulmonary involvement. Anti-GBM disease is classically diagnosed by both demonstrating GBM linear immunofluorescence staining on kidney biopsy and detecting anti-GBM antibodies in serum. More than 90% of patients with anti-GBM disease either become dialysis-dependent or die if left untreated.Here, we report a 37-year-old man who presented with bilateral lower limb edema, hypertension, acute kidney injury (creatinine of 212 μmol/L), microscopic hematuria, and nephrotic range proteinuria (15 g/day). His kidney biopsy showed diffuse crescentic membranoproliferative glomerulonephritis and bright linear staining of GBM by immunoglobulin G consistent with anti-GBM disease; however, serum anti-GBM antibodies were negative. The patient was diagnosed with atypical anti-GBM disease and treated aggressively with intravenous pulse steroids, plasmapheresis, oral cyclophosphamide, and oral prednisolone with significant improvement in kidney function and proteinuria.Atypical anti-GBM disease should be considered in patients presenting with RPGN, even in the absence of serum anti-GBM antibodies. Early diagnosis and aggressive treatment in such cases are warranted to prevent irreversible kidney damage as the course of the disease might not be as benign as previously thought.

Prognostic factors in glomerular diseases with crescents.

More than 50% of glomerular crescent formation is required for a diagnosis of crescentic glomerulonephritis in a kidney biopsy. Although treatment protocols have been established for diffuse crescentic glomerulonephritis, there is no standard treatment for patients with fewer crescents in renal biopsies. In this study the importance of crescent percentage and clinical features on renal survival independent of underlying disease was investigated. This retrospective observational study was conducted between 2013 and 2017. Forty-nine patients with crescent formation in their kidney biopsies were evaluated. We compared clinicopathological features and renal survival. We evaluated the factors affecting the course of end stage renal disease (ESRD). A total of 49 patients (57% male and median age 49 years) were enrolled in this study. 39% of patients developed ESRD at follow-up. Logistic regression analysis showed that the requirement for renal replacement treatment on admission (p < 0.001), serum creatinine level above 2.7 mg/dL (p < 0.001), the presence of more than 50% glomerulosclerosis (p = 0.04) and more than 34% crescent formation (p = 0.002) were significantly associated with ESRD. Kaplan-Meier survival analysis revealed that patients with less than 34% crescent in kidney biopsy and a serum creatinine level less than 2.7 mg/dL had increased kidney survival (log-rank test p: 0.01 and p: 0.002). Patients with crescent formation in kidney biopsy more than 34% should be evaluated for more aggressive treatment modalities regardless of the underlying disease, especially if the serum creatinine level is above 2.7 mg/dL.

A case of aggressive atypical anti-GBM disease complicated by CMV pneumonitis

BackgroundAnti-glomerular basement membrane (anti-GBM) disease is characterized by circulating IgG glomerular basement membrane antibodies and is clinically expressed as a rapidly progressive crescentic glomerulonephritis (GN), with 30–60% of patients also developing pulmonary hemorrhage. Classically, the renal biopsy shows glomerular crescent formation, bright linear staining of glomerular basement membranes (GBM) for IgG on direct immunofluorescence (IF), and the serologic presence of circulating anti-GBM antibodies. Recently, patients with linear IgG IF staining, undetectable circulating anti-GBM antibodies and glomerular changes atypical for anti-GBM disease have been described as “atypical anti-GBM disease”, with a distinctly more benign clinical course than typical anti-GBM disease. We present a case report of a patient with negative anti-GBM serology but positive linear IgG staining by IF, severe diffuse crescentic and endocapillary proliferative glomerulonephritis, and renal failure, complicated by severe pulmonary hemorrhage after immunosuppression, likely due to cytomegalovirus (CMV) pneumonitis.Case presentationA 24-year-old man was admitted to hospital with hemoptysis and renal failure. Investigations for anti-GBM serology by addressable laser bead immunoassay (ALBIA) was negative for anti-GBM antibodies. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with membranoproliferative features and diffuse circumferential crescents. Direct IF showed strong linear staining for IgG along GBMs. The patient’s hemoptysis improved with immunosuppression, but 1 month later he was readmitted with gross hemoptysis, which was refractory to further cyclophosphamide, plasma exchange and rituximab. Bronchoalveolar lavage (BAL) and blood work confirmed CMV pneumonitis, and the patient’s hemoptysis resolved with ganciclovir, though he became dialysis dependent.ConclusionsThis case demonstrates an atypical presentation of anti-GBM disease with both crescents and endocapillary hypercellularity and negative serology. The patient is dialysis dependent, unlike most previously described patients with atypical anti-GBM disease. The course was complicated by CMV pneumonitis, which contributed to the severity of the pulmonary manifestations and added diagnostic difficulty.

A case of crescentic glomerulonephritis associated with relapsing polychondritis

Relapsing polychondritis (RP) is a rare autoimmune disease, characterized by recurrent inflammatory episodes affecting various carttilageus structures. Renal involvement in RP is unusual. Our case was a 42-year old woman presented with nephretic syndrome. Diagnosis of RP was made because of recurrent chondritis of both auricles, chondritis of costovertebral joints, non-erosive inflammatory arthritis of knees, and inflammation of ocular structures. Renal biopsy findings revealed diffuse crescentic and sclerotic glomerulonephritis, pauciimmune type. The diagnosis of RP may be missed when the destructive cartilage feature is not apparent or rare presentation of disease such as ocular or renal involvement preceded other manifestations. In this case we found that the irregular prednisolone use may prevent destructive cartilage damage but not renal failure of patient. We concluded that the association of crescentic glomerulonephritis in a patient with RP was assumed to be a rare manifestation of this disease.

Clinicopathological Characteristics and Outcomes of Diffuse Crescentic Glomerulonephritis - A Single Center Experience from Southern India.

Diffuse Crescentic glomerulonephritis (CrGN) is characterized by rapidly progressive renal failure and has grave prognosis. There is significant regional and temporal variation in aetiology, prevalence and prognosis of diffuse crescentic glomerulonephritis (CrGN) with limited data available in adult Indian population. This study aims to identify the aetiology, clinico-pathological features and outcomes of diffuse CrGN in south Indian population. In this retrospective study, clinical records of all adults (>18 years) over a 5-year period (2010-2014) with a histopathological diagnosis of diffuse CrGN (>50% crescents) were reviewed. Clinical, serological, biochemical and histopathological data were collected. Follow-up data at six months including renal outcome and mortality were studied. Data was analysed using SPSS version 15. There were 29 cases of diffuse CrGN accounting for an incidence of 2.9% among 1016 non-transplant kidney biopsies. The most common cause was pauci-immune crescentic GN. The median creatinine at admission was 7.2 mg/dl {(interquartile range (IR) 3.3 - 10.4)} and 75.9% of patients required haemodialysis at admission. Complete/partial recovery was seen in 34.5%. At the end of six months 31% were dialysis dependent and the mortality was 27.6%. On univariate analysis, the significant predictors of renal loss and mortality were oliguria (p=0.02), requirement of haemodialysis and serum creatinine (p=0.001) at admission (>5.5mg/dl) (p=0.003). Histopathological features did not influence the outcome in our study. In our cohort, the most common cause for diffuse CrGN is pauci-immune CrGN. Diffuse CrGN carries a poor prognosis. Patients with pauci-immune and AntiGBM disease have worst prognosis compared to immune complex CrGN. The presence of oliguria, high serum creatinine and requirement of haemodialysis at admission are associated with poor outcomes.

Severe Uncompensated Metabolic Alkalosis due to Plasma Exchange in a Patient with Pulmonary-Renal Syndrome: A Clinician's Challenge.

Metabolic alkalosis secondary to citrate toxicity from plasma exchange is very uncommon in patients with normal renal function. In patients with advanced renal disease this can be a fatal event. We describe a case of middle-aged woman with Goodpasture's syndrome treated with plasma exchange who developed severe metabolic alkalosis. High citrate load in plasma exchange fluid is the underlying etiology. Citrate metabolism generates bicarbonate and once its level exceeds the excretory capacity of kidneys, the severe metabolic alkalosis ensues. Our patient presented with generalized weakness, fever, and oliguria and developed rapidly progressive renal failure. Patient had positive serology for antineutrophilic cytoplasmic antibodies myeloperoxidase (ANCA-MPO) and anti-glomerular basement membrane antibodies (anti-GBM). Renal biopsy showed diffuse necrotizing and crescentic glomerulonephritis with linear glomerular basement membrane staining. Patient did not respond to intravenous steroids. Plasma exchange was started with fresh frozen plasma but patient developed severe metabolic alkalosis. This metabolic alkalosis normalized with cessation of plasma exchange and initiation of low bicarbonate hemodialysis. ANCA-MPO and anti-GBM antibodies levels normalized within 2 weeks and remained undetectable at 3 months. Patient still required maintenance hemodialysis.

Goodpasture’s syndrome with concomitant immune complex mixed membranous and proliferative glomerulonephritis

Classical Goodpasture's (GP) syndrome is a monophasic illness characterized by pulmonary hemorrhage and rapidly progressive glomerulonephritis with linear IgG deposition along the glomerular and distal tubular basement membrane and estructive necrotizing diffuse extracapillary crescentic glomerulonephritis. The majority of patients have circulating anti-glomerular basement membrane (GBM) antibodies, detectable with standard anti-GBM ELISA. Concurrence of GP syndrome with proliferative glomerulonephritis has only rarely been described. In this report, for the first time we describe in a 21-year-old woman GP syndrome with 50% crescentic sclerosing glomerulonephritis with linear immunofluorescence characteristic of anti-GBM pathogenesis, combined with mixed membranous and membranoproliferative glomerulonephritis with granular immunofluorescence and subepithelial, mesangial and subendothelial deposits characterizing immune complex pathogenesis. The clinical picture was also unusual for GP syndrome, manifesting a recurrent but non-progressive course, nephrotic syndrome, normal renal function and low values of anti-GBM antibodies, identified only by novel more sensitive techniques.

Pulmonary hemorrhage complicating Goodpasture’s disease in the course of pulmonary tuberculosis

A 72-year-old man with ESRD on hemodialysis was referred to the hospital because of hemoptysis. A chest radiograph showed diffuse infiltration in the right lung field. Laboratory data showed hematuria and proteinuria. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgG along the glomerular basement membrane (GBM). However, circulating IgG anti-GBM antibodies were not detected. Because the findings of renal biopsy suggested Goodpasture's disease, the patient was treated with plasmapheresis and pulse steroid therapy, which resulted in a rapid resolution of his pulmonary symptoms and chest radiograph abnormalities. However, sputum culture on admission yielded Mycobacterium tuberculosis 3 weeks later. Therefore, immuosuppressive agents were discontinued and antituberculous agents were administered. There was no relapse of pulmonary hemorrhage during the next 1-year period of follow-up, but the patient did not regain renal function and remained on hemodialysis.

An unusual case of IgA-mediated anti-glomerular basement membrane disease

Anti-glomerular basement membrane (GBM) disease is mediated by circulating autoantibodies, principally IgG, targeted at the type IV collagen of GBM. The IgA variant of anti-GBM disease has rarely been described. We report a 65-year-old man with uremia, undergoing hemodialysis, who was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis. Circulating IgA anti-GBM antibody was found, as well as the presence of significant IgA deposition in a linear pattern along the GBM, suggesting an anti-GBM antibody-mediated disease. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.

IgA Variant of Anti-glomerular Basement Membrane Glomerulonephritis Associated with Pulmonary Hemorrhage and Microangiopathic Hemolytic Anemia

A 70-year-old man with uremia was referred because of hemoptysis. A chest X-ray showed diffuse infiltration in the right lung field. Laboratory data were remarkable for renal failure, anemia, and thrombocytopenia. Furthermore, laboratory evidence of microangiopathic hemolytic anemia was present. A kidney biopsy revealed diffuse crescentic glomerulonephritis with linear staining of IgA along the glomerular basement membrane (GBM). No thrombotic microangiopathy was noted on renal biopsy. Circulating IgG anti-GBM antibody was not detected, and IgA anti-GBM antibody was not tested. The patient was treated with plasmapheresis and pulse steroid therapy, which resulted in an immediate improvement in the pulmonary hemorrhage and hematological abnormalities. However, the patient did not regain renal function and remained on hemodialysis.

Pulse療法,血漿交換法,ヘパリン持続静注法により著明に改善した抗GBM抗体型急速進行性糸球体腎炎の1例

The patient, a 28 year-old-man, was admitted to a hospital because of general fatigue and fever. He was pointed out renal dysfunction and was transferred to Nagasaki University Hospital. The laboratory data on admission showed moderate azotemia (BUN 43 mg/dl, Cr 5.4 mg/dl). A percutaneous renal biopsy on admission revealed a diffuse crescentic glomerulonephritis. A direct immunofluorescence of renal biopsy showed a linear pattern for IgG along the glomerular basement membrane. Radioimmunoassay of his serum for circulating anti-GBM antibody was strongly positive. Aggressive treatment with pulse therapy (methylprednisolone), plasmapheresis, and continuous heparin infusion was performed. He had markedly recovered from renal failure and escaped hemodialysis. The patient is making satisfactory process after 3 years.

A case of pregnancy‐induced thrombotic thrombocytopenic purpura with a kidney allograft recipient

A 32-yr-old female patient, who had been suffering from diffuse crescentic glomerulonephritis and a consequent end-stage renal disease, successfully underwent living-related ABO-incompatible kidney transplantation after a desensitization therapy including anti-CD20 monoclonal antibody. Forty-six months after the transplantation, the recipient became pregnant. At the 17th gestational week, the patient was admitted for the management of pregnancy-induced hypertension and aggressive deterioration of kidney graft function. At the 21st gestational week, the patient lost her kidney graft and was re-induced into regular hemodialysis. The patient was also suffering from progressive hemolytic anemia, thrombocytopenia, and neurologic symptoms with decreased activity of von Willebrand factor-cleaving protease, a disintegrin-like and metalloprotease with thrombospondin type 1 motifs 13 (ADAMTS13). From these findings and a kidney allograft biopsy, the patient was diagnosed as thrombotic thrombocytopenic purpura concurrent with acute T-cell-mediated rejection. The patient immediately underwent plasma exchange as well as steroid pulse therapy. Despite these treatments, thrombocytopenia and intrauterine growth retardation progressed. The patient underwent a caesarian section at the 24th gestational week. Consequently, her platelet count recovered drastically. However, the patient lost her neonate five d after giving a birth, and the patient's graft function had never recovered.

Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis

The objectives of the study are to investigate the clinical features and renal outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN). Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal outcomes were investigated. There were 84 females and 10 males, with a mean age of 27.9 ± 10.7 years old. They represented: hypertension in 73 cases (77.7%), rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic syndrome needed dialysis therapy. There were 25 cases received repeated renal biopsy. Their histological examination showed the decreasing of active lesions and the increasing chronic lesions. All patients were more than 6 months follow-up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time of follow-up (3 months), the renal function, proteinuria, and anemia were improved significantly in all of cases received intensive immunosuppressive therapy. At the last time of follow-up (56.1 ± 18.8 months), only four patients eventually developed to the end-stage renal failure and five died with normal renal function. The lupus patients with DCGN presented more severe clinical syndromes, which were similar to those patients of type II of DCGN. The relative good renal outcomes were observed in those lupus patients, to which may be contribute to the effective induction therapy.

Glomerular diseases in renal biopsy. Correlation of clinical syndromes with histological types

Renal biopsies studied by light and electron microscopy as well as by immunohistochemistry seem to be continually necessary for an adequate typing and therapy of glomerulonephritis (GN) and other glomerular diseases. Basing on 653 renal biopsies examined in Rostock from 1990 to 1999, the morphological classification in a total of 585 cases with glomerular diseases is presented in comparison to their clinical syndromes according to the WHO classification. A nephrotic syndrome was most frequent and clinically reported in 258 of the 585 biopsy cases with glomerular diseases (44%). It was seen in 77 of the 87 cases with minimal change nephropathy (55%), in 46 of the 74 cases with focal segmental glomerulosclerosis (62%), and in 19 of the 24 diffuse membranous GN cases (79%). The majority of the varying histological subtypes of diffuse GN was not combined with a specific clinical syndrome except of diffuse crescentic GN presenting with a rapidly progressive nephritic syndrome in 14 of 16 cases (88%). IgA nephropathy was the most often diagnosed entity of glomerular diseases found in 122 of the 502 cases with primary or secondary GN (24%). It is obvious that a given morphological GN type can but must not be combined with a specific clinical GN syndrome, so that the clinical importance of renal biopsy is stressed.

Histologic and immunohistologic study and clinical presentation of ANCA-associated glomerulonephritis with correlation to ANCA antigen specificity

Background: The major antigen specificities of antineutrophil cytoplasmic antibodies (ANCA) are for proteinase 3 (PR3) and myeloperoxidase (MPO). Only a limited number of studies have systematically assessed renal pathology with respect to ANCA antigen specificity. Methods: The authors evaluated renal biopsy light microscopy and immunofluorescence findings, clinical presentation, and outcome in 135 patients with ANCA-associated vasculitides. Results: Patients were divided into 3 groups: PR3-ANCA (n = 55), MPO-ANCA (n = 74), and ANCA of other specificities (n = 6). The mean duration of renal disease at biopsy was significantly longer in patients with MPO-ANCA than in those with PR3-ANCA (6.9 v 3.0 months). Immunofluorescence results showed mostly pauci-immune glomerulonephritis (n = 129) and rarely diffuse granular glomerular immune deposits suggesting immune complex deposition (n = 6). A focal form of crescentic glomerulonephritis was more frequent (P < 0.001), and glomerular necrosis was more prominent (P = 0.013) in the PR3-ANCA group, whereas diffuse crescentic glomerulonephritis, glomerulosclerosis, and interstitial fibrosis predominated in the MPO-ANCA group (P < 0.001). Extraglomerular vasculitis, present in 22.2%, and chronic vascular lesions indicative of previous vasculitis, present in 11.9% of patients, correlated with systemic involvement. Conclusion: The evolution of the pathologic lesions of PR3-ANCA and MPO-ANCA-associated glomerulonephritis seems to be similar. Differences in histopathology could be explained by the observation that in patients with PR3-ANCA, kidney biopsy was performed soon after renal involvement appeared, and focal active lesions were prevalent, whereas in patients with MPO-ANCA, kidney biopsy was done late in the course of the disease, and diffuse chronic sclerotic lesions predominated. Renal extraglomerular small vessel vasculitis appeared to be predictive of systemic involvement. Am J Kidney Dis 41:539-549. © 2003 by the National Kidney Foundation, Inc.

Idiopathic IgA Nephropathy with Diffuse Crescent Formation

Objective: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. Methods: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. Results: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 ± 264 µmol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50–95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans’ capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 µmol/l), and only 5 were dialysis-dependent. Conclusions: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.