Successful treatment with steroid and cyclosporine A in a patient with immunoglobulin A–proliferative glomerulonephritis with monoclonal immunoglobulin deposits

We report a case of glomerulonephritis with monoclonal immunoglobulin (Ig) A deposits as a form of monoclonal gammopathy of renal significance (MGRS) caused by monoclonal immunoglobulins without blood disorders in a 41‐year‐old woman. She developed lower leg oedema and was hospitalized because of nephrotic syndrome. Serum and urine were negative for M protein, and the free light chain κ/λ ratio was within the normal range. Renal histopathological findings included mesangial proliferation, endocapillary cell proliferation, and a double‐contour appearance of the capillary walls. Immunofluorescent staining indicated IgA and C3 deposits on the mesangium and capillary walls. Only λ chain and IgA1 deposits were noted. Fine granular sub‐endothelial deposits with no specific structure were observed under electron microscopy. The patient was diagnosed with IgA–proliferative glomerulonephritis with monoclonal immunoglobulin deposits (IgA‐PGNMID). The patient had decreased urine protein and sediment erythrocytes after she underwent two rounds of steroid pulse therapy and oral steroid therapy, but proteinuria and haematuria still remained. Four months later, the patient was administered 50 mg/day cyclosporine (CsA), and proteinuria and haematuria dramatically decreased. Only a few case reports have been published on IgA‐PGNMID. This case is rare in that the patient achieved successful treatment using a combination of steroids and CsA.     

Human Parvovirus B19-Induced Acute Glomerulonephritis: A Case Report

Human parvovirus B19 (HPV B19) infection is well known as a cause of erythema infectiosum in children. Acute glomerulonephritis due to HPVB19 infection is rarely observed in adults. Here, we present the case of a 45-year-old female who showed acute glomerulonephritis induced by HPVB19 infection with various autoantibodies. She had proteinuria (175 mg/g creatinine) and hematuria (20–29 erythrocytes per high-power field) in a urinalysis, and various autoantibodies such as antinuclear antibodies, proteinase-3-antineutrophil cytoplasmic antibodies (PR3-ANCA), antiglomerular basement membrane (GBM) antibodies, and anticardiolipin antibodies in a blood examination. A renal biopsy showed that endocapillary proliferative glomerulonephritis comprised of mononuclear cell infiltration. By using immunofluorescence microscopy, IgG, IgA, IgM, C3, C4, and C1q deposits were detected mainly in glomerular capillaries. Electron-dense deposits were detected in the subendothelial area and mesangial area by using electron microscopy. All symptoms and abnormal laboratory data were self-improved. Our patient’s case may provide a clue to the etiology of ANCA-associated vasculitis or lupus nephritis.     

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.     

Proliferative glomerulonephritis with monoclonal IgG deposits: a distinct entity mimicking immune-complex glomerulonephritis

BACKGROUND: Renal disease related to the deposition of monoclonal immunoglobulins containing both heavy and light chains can occur in type 1 cryoglobulinemia, Randall type light and heavy chain deposition disease (LHCDD), and immunotactoid glomerulonephritis. We report a novel phenotype of glomerular injury that does not conform to any of the previously described patterns of glomerular involvement by monoclonal gammopathy. METHODS: Ten cases of unclassifiable proliferative glomerulonephritis manifesting glomerular monoclonal immunoglobulin G (IgG) deposits were identified retrospectively from the archives of the Renal Pathology Laboratory of Columbia University over the past 3 years (biopsy incidence 0.21%). RESULTS: The monoclonal immunoglobulins formed granular electron dense deposits in mesangial, subendothelial, and subepithelial sites, mimicking ordinary immune complex-mediated glomerulonephritis and producing a diffuse endocapillary proliferative or membranoproliferative glomerulonephritis. However, by immunofluorescence, the deposits were monoclonal, staining for a single light chain isotype and a single gamma subclass (including two IgG1kappa, one IgG1lambda, one IgG2lambda, four IgG3kappa, and one IgG3lambda). All cases stained for the three constant domains of the gamma heavy chain (CH1, CH2, and CH3), suggesting deposition of a nondeleted immunoglobulin molecule. Tissue fixation of complement was observed in 90% of cases, and 40% of patients had hypocomplementemia. Clinical presentations included renal insufficiency in 80% (mean serum creatinine 2.8 mg/dL, range 0.9 to 8.0), proteinuria in 100% (mean urine protein 5.8 g/day; range 1.9 to 13.0), nephrotic syndrome in 44%, and microhematuria in 60%. A monoclonal serum protein with the same heavy and light chain isotype as that of the glomerular deposits was identified in 50% of cases (including three IgGkappa and two IgGlambda); however, no patient had clinical or laboratory features of type 1 cryoglobulinemia. No patient had overt myeloma or lymphoma at presentation or over the course of follow-up (mean 12 months). CONCLUSION: Glomerular deposition of monoclonal IgG can produce a proliferative glomerulonephritis that mimics immune-complex glomerulonephritis by light and electron microscopy. Proper recognition of this entity requires confirmation of monoclonality by staining for the gamma heavy chain subclasses.     

Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

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.     

Patient with diffuse mesangial and endocapillary proliferative glomerulonephritis with hypocomplementemia and elevated anti-streptolysin O treated with prednisolone, angiotensin-converting enzyme inhibitor, and angiotensin II receptor antagonist

A 24-year-old woman was admitted to Toyosaka Hospital with proteinuria, hematuria, lymphopenia, hypocomplementemia, positive anti-nuclear antibody (ANA), and elevation of anti-streptolysin O (ASO). Renal biopsy specimen revealed diffuse mesangial and endocapillary glomerulonephritis with crescent formation and duplication of the capillary loop on light microscopic examination. Mild to moderate proliferation of mesangial matrix and cells were observed. On immunofluorescence (IF) examination, deposition of IgG, IgA, IgM, C1q, C3, and C4 to the mesangium and capillary wall were observed. By electron microscopy (EM), mesangial, subendothelial, and subepithelial deposits were recognized. However, microtubular structure in glomerular endothelial cells, fingerprint structures, and circumferential mesangial interposition were not observed by EM. The patient was referred to our hospital, but there was no change in her proteinuria 3 weeks after admission. The elevation of ASO, hypocomplementemia, and endocapillary proliferation suggested acute glomerulonephritis, while lymphocytopenia, positive ANA, the persistent hypocomplementemia, and various deposits detected by IF and EM suggested lupus nephritis; however, she did not fulfill the classification criteria of systemic lupus erythematosus. We started prednisolone (40mg/day) with the diagnosis of chronic glomerulonephritis revealing diffuse mesangial and endocapillary proliferative glomerulonephritis, but it was not effective for the proteinuria. Quinapril (10mg/day) and losartan (25 to 50mg/day) were administered and the proteinuria decreased. It is possible that this use of an angiotensin converting-enzyme inhibitor and an angiotensin II receptor antagonist was effective in reducing the proteinuria in this patient.     

Rapid development of diffuse crescents in post-streptococcal glomerulonephritis

A 14-year-old boy presented with 3 days of hematuria and oliguria following impetigo. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with subendothelial electron dense deposits but no crescents. Due to recrudescence of clinical abnormalities after initial improvement, the patient was re-biopsied 10 days later. This biopsy showed circumferential crescents in 83% of the glomeruli. Treatment with intensive plasma exchange, prednisolone, cyclophosphamide and dipyridamole was accompanied by prompt improvement in renal function. The need to carefully monitor the course in patients with acute post-streptococcal glomerulonephritis is emphasized.     

Glomerular disease in cirrhosis of the liver: low frequency of IgA deposits

Twelve HBsAg-negative patients with histologically documented cirrhosis of the liver of either alcoholic (8 of 12) or cryptogenic (4 of 12) origin underwent renal biopsy to investigate proteinuria, hematuria and/or renal failure. Immunofluorescence was positive for IgA in 2 patients with mesangiocapillary glomerulonephritis (MCGN) and could not be performed in 2 additional patients with the same diagnosis. However, in the remaining 8 patients, immunofluorescence was negative for IgA and frequently positive for C3, IgG, IgM and/or fibrinogen. These 8 patients without IgA were classified as follows: MCGN with subendothelial electron-dense deposits (2 cases), IgM-IgG cryoglobulinemia with diffuse endocapillary glomerulonephritis (1 case), membranous nephropathy (1 case), diffuse endocapillary proliferative glomerulonephritis (1 case), vasculitis with focal segmental necrotizing glomerulitis and crescentic glomerulonephritis (2 cases). These results show that cirrhosis of the liver can be associated with a wide variety of glomerular disorders. Contrary to previous belief, IgA is absent in two thirds of patients with cirrhosis and glomerulopathy. Therefore, the pathogenetic importance of IgA in the development of glomerular disease in such patients is doubtful.     

Diffuse proliferative glomerulonephritis after bone marrow transplantation

A 15-year-old boy developed nephrotic syndrome and acute renal failure 4 years after allogenic bone marrow transplantation (BMT) for lymphoid crisis of chronic myelocytic leukemia. On admission, he presented with clinical features of chronic GVHD including transient exacerbation of cholestatic liver injury. Renal biopsy showed diffuse proliferative glomerulonephritis with cellular crescents. The patient was treated with methylprednisolone pulse therapy (1 g/day, for 3 days) followed by oral prednisolone. Renal function gradually improved but nephrotic state was persistent. A second renal biopsy showed improvement of acute tubular necrosis and endocapillary proliferation and transformation of crescents into a fibrous form. After tapering of oral prednisolone, cyclophosphamide was started, which resulted in a gradual improvement of proteinuria. Several cases of nephrotic syndrome occurring after BMT have already been reported, but most cases had membranous nephropathy. In our case, renal biopsy revealed diffuse proliferative glomerulonephritis with findings of active cellular immunity, and aggressive treatment resulted in attenuation of these findings. Moreover, chronic GVHD-related liver injury was noted at the time of this episode. Our findings suggest that chronic GVHD may be complicated with diffuse proliferative glomerulonephritis through unknown cellular immune mechanism.     

Renal involvement of monoclonal immunoglobulin deposition disease associated with an unusual monoclonal immunoglobulin A glycan profile

A 38-year-old man was admitted to the hospital for the evaluation of proteinuria, microscopic hematuria, and monoclonal IgA-κ gammopathy. The initial renal pathological findings showed mesangial proliferative glomerulonephritis with endocapillary proliferation, a necrotizing lesion, and cellular crescent formation accompanied by IgA1-κ deposition in the mesangium. Neither typical immune-complex deposits nor organized-structure deposits were detected. We diagnosed the patient with monoclonal immunoglobulin deposition disease (MIDD) associated with monoclonal IgA (mIgA). After the initiation of a monthly treatment with melphalan and predonisolone (MP therapy), the patient’s serum IgA levels declined, and clinical remission was ultimately achieved. The follow-up renal biopsy showed reduced IgA-κ staining, and both the endocapillary proliferation and the necrotizing lesion had disappeared. To elucidate the mechanism of IgA deposition, we investigated the glycan profile of the patient’s serum mIgA using a mass spectrometry technique. The results revealed an unusual N-glycan profile compared to that of another patient with circulating mIgA lacking renal involvement and that of a healthy control. mIgA deposition in the mesangial area is a rare disease, and the glycan profiling of MIDD with renal involvement has not been reported previously. Thus, the present case suggests that any variation in Ig glycosylation may be a step in the pathogenesis of MIDD with renal involvement and/or contribute to some cases of IgA nephropathy.     

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.     

Glomerular podocytopathy in patients with systemic lupus erythematosus

A series of patients with systemic lupus erythematosus (SLE) and proteinuria were studied to determine whether nephrotic-range proteinuria was associated with diffuse epithelial cell foot process effacement in the absence of peripheral glomerular immune aggregate deposition. Biopsies from patients with known or suspected SLE and a histologic diagnosis of (1) normal by light microscopy, (2) mesangial proliferative glomerulonephritis, or (3) focal segmental glomerulosclerosis were studied. Biopsies were excluded when they demonstrated endocapillary proliferation or necrosis by light microscopy or electron-dense glomerular basement membrane deposits by electron microscopy. Patients were required to fulfill four of 11 American Rheumatologic Association criteria for the diagnosis of SLE, and proteinuria could not be associated with nonsteroidal anti-inflammatory drug use. Eighteen biopsies were studied, eight from patients with nephrotic-range proteinuria (>/=3 g/d) and 10 from patients with non-nephrotic proteinuria. The time from diagnosis of SLE to biopsy was shorter for nephrotic patients that for nonnephrotic patients. Seven of eight biopsies from nephrotic patients demonstrated at least 80% foot process effacement, whereas no biopsy from a nonnephrotic patient exhibited >20% effacement. There were no other significant pathologic differences between the nephrotic and nonnephrotic patients. The single common morphologic feature associated with nephrotic proteinuria was diffuse visceral epithelial cell foot process effacement. It is concluded that the development of nephrotic-range proteinuria in patients with SLE without peripheral immune aggregate deposition or endocapillary proliferation on renal biopsy is more likely a manifestation of SLE than the coexistence of idiopathic minimal-change glomerulopathy and SLE.     

Glomerulonephritis in diabetic patients and its effect on the prognosis

Renal biopsies were obtained from 164 patients with diabetes mellitus. Their histological changes were evaluated together with clinical findings and prognosis. In 36 patients, various types of glomerulonephritis were complicated: mesangial proliferative glomerulonephritis (17 patients), membranous glomerulonephritis (8), endocapillary proliferative glomerulonephritis (5), membranoproliferative glomerulonephritis (4) and minimal change nephrotic syndrome (2). Superimposed glomerulonephritis was suspected in diabetic patients with a short history of less than 5 years, persistent proteinuria, occasional hematuria and no retinopathy. They may, however, produce little effects on the long-term prognosis of diabetic patients except membranoproliferative glomerulonephritis.     

Development of glomerulonephritis during anti-TNF-alpha therapy for rheumatoid arthritis.

BACKGROUND: Treatment of rheumatoid arthritis with anti-tumour necrosis factor alpha (TNFalpha) agents may lead to autoantibody formation and flares of vasculitis, but renal complications are rare. METHODS: We report the clinical and pathologic findings in five patients with longstanding rheumatoid arthritis (duration of rheumatoid arthritis, 10-30 years; mean, 23 years) who developed new onset of glomerular disease after commencing therapy with anti-TNFalpha agents (duration of therapy, 3-30 months; median, 6 months). RESULTS: At presentation, three patients were receiving etanercept, one adalimumab and one infliximab. Two subjects presented with acute renal insufficiency, haematuria, nephrotic-range proteinuria, positive lupus serologies, and hypocomplementemia, and renal biopsies showed proliferative lupus nephritis. Two individuals presented with new onset renal insufficiency, haematuria and proteinuria, and renal biopsies showed pauci-immune necrotizing and crescentic glomerulonephritis. One of these subjects, who had anti-myeloperoxidase autoantibodies, also developed pulmonary vasculitis. The fifth patient presented with nephrotic syndrome and renal biopsy findings of membranous glomerulonephritis, associated with immune complex renal vasculitis. A pathogenic role for anti-TNFalpha therapy is suggested by the close temporal relationship with development of glomerular disease, and by the improvement in clinical and laboratory abnormalities after drug withdrawal and initiation of immunosuppressive therapy in most cases. CONCLUSIONS: Rheumatoid arthritis patients receiving anti-TNFalpha agents may develop glomerulonephritis via the induction of rheumatoid arthritis-related nephropathy or de novo autoimmune disorders.     

Henoch-Sch?nlein purpura complicating staphylococcal endocarditis in a heroin addict

A 21-year-old heroin addict with right-sided staphylococcal endocarditis developed skin purpura, abdominal pain, bloody diarrhea, proteinuria and microscopic hematuria. Skin biopsy showed leukocytoclastic vasculitis with IgA deposits in dermal vessels and renal biopsy disclosed proliferative glomerulonephritis with granular mesangial IgA and fibrinogen deposition. These features are typical of Henoch-Sch?nlein purpura. Symptoms abated spontaneously. Since the syndrome appeared during cloxacillin therapy, both this drug or the infectious disease itself could have triggered the immune response. Henoch-Sch?nlein purpura is a distinct clinical entity that can complicate the course of staphylococcal endocarditis.     

遗传性IgM肾病一家系三例报告及文献复习

目的 加强对遗传性IgM肾病的认识。方法 首次报道国内3例遗传性IgM肾病。对患者进行家系分析，对肾活检组织进行光镜、免疫荧光、电镜观察。对有关文献进行复习。结果 3例患者肾活检病理光镜表现为不同程度的系膜增殖性肾小球肾炎，免疫荧光提示IgM、C3在系膜区沉积。家系调查发现家族中还有10例患者有肾损害表现，均表现为血尿、蛋白尿，其中1例因尿毒症而死亡。结论 经病理检查和家系分析确诊为遗传性IgM肾病。结合文献复习提示遗传因素可能参与IgM肾病的发病机制。     

Mycophenolate mofetil in children with multidrug-resistant nephrotic syndrome

AIM: The aim of the present study is to report our clinical experiences with MMF in problematic children with chronic glomerulonephritis resistant to corticosteroids and/or other immunosuppressive drugs. PATIENTS AND METHODS: Ten patients with chronic glomerulonephritis resistant to treatment with corticosteroids and other immunosuppressive drugs were treated with mycophenolate mofetil (MMF). Causes of chronic glomerulonephritis were mesangial proliferative glomerulonephritis (4), membranoproliferative glomerulonephritis (3), chronic sclerosing glomerulonephritis (1), focal segmental glomerulosclerosis (1), diffuse endo- and extracapillary proliferative glomerulonephritis (1). MMF 15 mg/kg was used in combination with low-dose corticosteroids and angiotensin-converting enzyme inhibitors. RESULTS: During 24 weeks of MMF therapy, no significant changes were detected in mean serum creatinine, albumin and proteinuria. Severe leukopenia was seen in 1 patient. Additional adverse effects, including nausea and diarrhea, were observed in another patient when the dosage was increased to 20 mg/kg per day. During MMF treatment proteinuria decreased slightly without remission in 6 of 10 patients. CONCLUSION: Further data and clinical trials are needed to evaluate the possible role of MMF in the treatment of chronic glomerulonephritis of similar etiologies in pediatric patients.     

水痘带状疱疹病毒相关性肾小球肾炎及脑炎一例报告及文献复习

目的 介绍1例水痘带状疱疹病毒相关性肾小球肾炎及脑炎病例。 方法 分析患者临床和肾脏病理资料,并复习有关文献。 结果 男性15岁患者,水痘发病后5 d出现急性肾炎综合征、肾病综合征表现及肾功能损害,血清补体C3下降。肾组织光镜检查诊断为毛细血管内增生性肾小球肾炎,伴足细胞增生及重度肾小管损伤;免疫荧光检查显示“满堂亮”;电镜检查见到多部位电子致密物。另外,电镜及Mann染色光镜检查还见到病毒样颗粒或（和）包涵体。血清病毒学检查水痘带状疱疹病毒（VZV）IgM抗体阳性。肾组织免疫组化染色和原位杂交显示肾小球及肾小管上皮细胞内存在VZV抗原及转录产物RNA。病程中患者曾多次出现癫痫发作,头颅磁共振检查及脑电图表现符合病毒性脑炎继发癫痫。所以本病例水痘-带状疱疹病毒相关肾炎及脑炎诊断成立。 结论 通过血清病毒学及组织病毒学多项检查证实本例为水痘-带状疱疹病毒相关性肾炎及脑炎,是首例报道。     

Immune complex deposits in ANCA-associated crescentic glomerulonephritis: a study of 126 cases

BACKGROUND: Necrotizing and crescentic glomerulonephritis related to antineutrophil cytoplasmic autoantibodies (ANCA) is typically referred to as "pauci-immune"; however, it is not unusual for renal biopsies in such cases to exhibit some immune complex deposition within glomeruli on immunofluorescence and/or electron microscopic study. The composition and intraglomerular localization of such deposits in ANCA-glomerulonephritis has not been widely studied, and their potential pathologic and clinical significance is not clear, although a possible synergistic effect between immune complexes and ANCA in producing more severe glomerulonephritis is suggested by some human and animal studies. METHODS: Electron micrographs from 126 renal biopsies showing necrotizing/crescentic glomerulonephritis characterized by positive ANCA serology [C-ANCA, anti-proteinase 3 (anti-PR3), or anti-myeloperoxidase (MPO)] or necrotizing arteritis in the absence of known ANCA results were examined for the presence, quantity, and location of electron-dense deposits. The presence or absence of such deposits was correlated with histologic findings (fraction of glomeruli with crescents and segmental necrotizing lesions, mesangial and endocapillary hypercellularity), immunofluorescence findings, and clinical data, including serum creatinine and 24-hour urine protein levels at the time of biopsy. RESULTS: Sixty-eight (54%) of these biopsies showed glomerular immune complex deposits on electron microscopy; 87% of the latter also showed positive immunofluorescence findings for at least one immunoglobulin or complement component, although staining was relatively mild in most instances (< or =2+ on a 0 to 4+ scale in all but eight cases). Nearly half of biopsies negative for deposits by electron microscopy also showed positive immunofluorescence findings, though even more so than in cases with deposits on electron microscopy the intensity of immunofluorescence staining in these biopsies was typically very weak (trace or trace to 1+ in most cases, none >2+). Hypercellularity within the glomerular tuft was seen in 50% of biopsies with deposits on electron microscopy but only 14% of those without deposits; in each group this was usually mild and mesangial. Notably, the presence of deposits on electron microscopy was associated with a higher median level of proteinuria (3.2 versus 1.3 g/24 hours, P < 0.0001) and a higher median percentage of glomeruli with crescents (62.5% versus 44.0%, P= 0.06). CONCLUSION: Immune complex deposits were found on electron microscopy in just over half of renal biopsies with crescentic glomerulonephritis associated with positive ANCA serology and/or necrotizing arteritis. Clinical correlations suggest that these immune complex deposits may somehow potentiate the effect of ANCA in producing glomerulonephritis.