Endocapillary Proliferative Glomerulonephritis Research Articles

Letter to the editor concerning the article “Renal endarteritis with acute endocapillary proliferative glomerulonephritis” by Kawaguchi et al., Clin Nephrol. 2012; 77: 151-155 and authors response

Letter to the editor concerning the article “Renal endarteritis with acute endocapillary proliferative glomerulonephritis” by Kawaguchi et al., Clin Nephrol. 2012; 77: 151-155 and authors response

Immunoglobulin A-dominant postinfectious glomerulonephritis in a patient with acute HIV syndrome

Immunoglobulin A-dominant postinfectious glomerulonephritis in a patient with acute HIV syndrome

C3 glomerulonephritis: clinicopathological findings, complement abnormalities, glomerular proteomic profile, treatment, and follow-up

C3 Glomerulonephritis (C3GN) is a recently described disorder that typically results from abnormalities in the alternative pathway of complement. Here, we describe the clinical features, kidney biopsy findings, alternative pathway abnormalities, glomerular proteomic profile, and follow-up in 12 cases of C3GN. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients with native kidney disease. In two patients, C3GN recurred within one year of transplantation and resulted in a decline in allograft function. Kidney biopsy mainly showed a membranoproliferative pattern; although both mesangial proliferative and diffuse endocapillary proliferative glomerulonephritis were noted. Alternative pathway abnormalities were heterogeneous; both acquired and genetic. The most common acquired abnormality was the presence of C3 nephritic factors, while the most common genetic finding was the presence of H402 and V62 alleles of Factor H. In addition to these risk factors, other abnormalities included Factor H auto-antibodies and mutations in CFH, CFI and CFHR genes. Laser dissection and mass spectrometry of glomeruli from patients with C3GN showed accumulation of alternative pathway and terminal complement complex proteins. Thus, C3GN results from diverse abnormalities of the alternative complement pathway leading to subsequent glomerular injury.

Proliferative glomerulonephritis with monoclonal immunoglobulin G3κ deposits in association with parvovirus B19 infection

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits is a recently described disease entity, characterized by nonorganized electron-dense deposits in glomeruli and immunofluorescence findings indicating monoclonal immunoglobulin G deposits. The pathogenesis of many cases of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits remains unknown. We herein report 2 patients with parvovirus B19 infection who developed acute nephritic syndrome with hypocomplementemia (patient 1) or persistent proteinuria and congestive heart failure (patient 2); however, neither patient had detectable levels of serum monoclonal immunoglobulin G. Renal biopsy in both patients showed diffuse endocapillary proliferative glomerulonephritis with monoclonal immunoglobulin G3κ deposits, and electron microscopy showed nonorganized electron-dense deposits mainly in the subendothelial and mesangial areas. Clinical symptoms, abnormal laboratory findings, and urinary abnormalities recovered spontaneously in both cases within 4 weeks. Our 2 cases may be the first reported patients with proliferative glomerulonephritis with monoclonal immunoglobulin G deposits possibly associated with parvovirus B19 infection. Virus infection-associated immune disorders could be implicated in the pathogenesis of proliferative glomerulonephritis with monoclonal immunoglobulin G deposits.

Analysis on clinical pathological prognosis of patients with acute post-infectious glomerulonephritis

Objective To investigate the variety of immunology course and prognostic factors and conditions in patients with acute post-infectious glomerulonephritis.Methods 131 patients with acute post-infectious glomerulonephritis in our hospital were selected and divided into two groups,rapidly progressive group with 53 patients (crescentic glomerulonephritis) and acute group with 78 patients (endocapillary proliferative glomerulonephritis).And we observed the urine routine examination,blood routine examination and blood biochemistry before treatment and 1 month post-treatment.The differences between two groups were compared to evalnate the clinical effects.Results ①The acute group had better urine routine examination,blood routine examination and blood biochemistry than control group before treatment (P＜0.05),the differences between two groups had statistical significance.②1 month post-treatment,the acute group had better urine routine examination,blood routine examination and blood biochemistry than control group (P＜0.05).Conclusions Patients with crescentic glomerulonephritis caused by acute infectious has severe early stage and worse prognosis than patients with endocapillary proliferative glomerulonephritis.Patients with crescentic glomerulonephritis should receive early treatment. Key words: Acute infection; Glomerulonephritis

Peculiar renal endarteritis in a patient with acute endocapillary proliferative glomerulonephritis

Acute glomerulonephritis (AGN) is one of the most common renal diseases. They are often associated with infections and can result in diffuse proliferative glomerulonephritis (GN). This case report reviews an interesting case in which renal endarteritis coexisted in AGN with diffuse endocapillary proliferation. The discussion highlights important pathological findings and clinical aspects in acute endocapillary proliferative GN with renal endarteritis. Coexisting endarteritis should be in the differential diagnosis of AGN in patients with persistent clinical courses.

Clinicopathologic Features of IgA-Dominant Postinfectious Glomerulonephritis

BackgroundIgA-dominant acute postinfectious glomerulonephritis (APIGN) is a recently recognized morphologic variant of APIGN, but its clinicopathologic features were not clearly characterized. We will present demographic, clinical and renal biopsy findings from seven patients with IgA-dominant APIGN with a literature review.MethodsAll renal biopsy specimens (n=1,119) processed by the Department of Pathology in Hanyang University Hospital from 2005 to 2009 were reviewed. Seven patients with IgA-dominant APIGN were identified, and their clinical data analyzed.ResultsAll patients had renal failure, hematuria and proteinuria. One was diabetic, and none of the patients had previous renal diseases. Three had clinical infections at the time of presentation: 2 with methicillin-resistant Staphylococcus aureus and one with rickettsial infection. Light microscopically diffuse endocapillary proliferative and exudative glomerulonephritis was found in all cases. Immunofluorescence microscopy showed granular IgA deposits along peripheral capillary walls and in mesangium. Ultrastructurally, subepithelial 'humps' with mesangial deposits were noted. End-stage renal disease developed in two patients, chronic renal failure was stationary in two, and azotemia improved in three.ConclusionsVarious infections including rickettsiosis preceded IgA-dominant APIGN in both diabetics and nondiabetics. Because the prognosis of IgA-dominant APIGN is poor, early diagnosis based on renal biopsy is required.

Acute Glomerulonephritis in an Immunocompetent Elderly Woman after Contact with a Child who Had Been Diagnosed as Erythema Infectiosum

The prevalence of postinfectious glomerulonephritis has decreased in most developed countries. We report the case of a previously healthy, immunocompetent 65-year-old woman who developed acute glomerulonephritis associated with human parvovirus B19 infection. She was referred by her primary care physician for suspected congestive heart failure but she had an elevated creatinine level and an abnormal urinalysis. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis. After biopsy, we learned that she had been in frequent contact with her grandson who had been diagnosed with erythema infectiosum. Her human parvovirus B19 serum IgM titer was elevated at 3.50, indicating current infection.

Frequency of primary glomerular disease in northeastern China

Most frequently reported Chinese renal biopsy data have originated from southeastern China. The present study analyzed the renal biopsy data from northeastern China. The records of 1550 consecutive native patients who were diagnosed with primary glomerular diseases (PGD) after renal biopsy at our hospital during 2005-2009 were used. These patients were divided into four age groups for stratified analysis: <15, 15-44, 45-59, and ≥60 years old. Among PGD, minimal change disease (MCD) was the most common histologically diagnosed disease (30.7%), followed by IgA nephropathy (IgAN), mesangial proliferative glomerulonephritis (MsPGN), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), focal segmental glomerulosclerosis (FSGS), and endocapillary proliferative glomerulonephritis (EnPGN). MCD was the disease most frequently observed (43.7%) in the <15-year-old group. MsPGN was the most common disease in the elderly group (38.1%). MsPGN was more prevalent in females (27.8%), whereas MCD was more prevalent in males (35.3%). Primary glomerular diseases constituted the most commonly encountered group of diseases with a high prevalence of MCD, which predominantly affected males and young adults. The prevalence of MCD was high in northeastern China. Further study is necessary to expand the epidemiologic data available for renal disease in China.

Post-infection immunocomplex glomerulonephritis and Legionnaires' disease in a patient with adult Still's disease during treatment with interleukin 1 receptor antagonist anakinra: a case report

IntroductionLegionellosis is a systemic disease that primarily affects the lungs. However, dysfunction in many organ systems, including the kidneys, has also been described. There are only a few reported cases of renal dysfunction in patients with legionellosis.Case presentationA 27-year-old Caucasian woman with known adult Still's disease was admitted to our hospital for community-acquired pneumonia, due to Legionella infection, with acute renal failure. Although her respiratory symptoms responded well to antibiotic treatment, her renal function worsened, with severe proteinuria and edema. A renal biopsy showed extracapillary and endocapillary proliferative glomerulonephritis with accompanying chronic and acute interstitial nephritis. This was consistent with a post-infection immunocomplex glomerulonephritis. After initiation of steroid therapy, her renal function improved. Additionally, therapy with diuretics and an angiotensin-converting enzyme inhibitor was initiated because of persistent proteinuria. Under this treatment regimen, her severe edema and proteinuria disappeared.ConclusionTo the best of our knowledge, there is only a handful of reported cases of post-infection glomerulonephritis with a nephrotic syndrome in a patient with legionellosis. Our findings suggest that, in patients with Legionnaires' disease with renal failure, post-infection immunocomplex glomerulonephritis should be considered and steroid therapy may be an effective modality to treat the renal complication.

Periodic fever syndrome with relapsing glomerulonephritis: a case report and teaching points.

We report a case of relapsing mesangial and endocapillary proliferative glomerulonephritis (GN) associated with a periodic fever syndrome. The patient presented 11 times in >4 years with acute febrile episode followed in 1–3 days by hematuria, thrombocytopenia and other symptoms of acute GN with variable severity of acute kidney injury. In three episodes, the patient required renal replacement therapy for 7, 10 and 2 treatments, respectively. Shortly after the acute symptoms of the febrile episode had resolved each time, the kidney function would recover and the serum creatinine would return to baseline. Two kidney biopsies obtained during separate episodes showed acute tubular injury along with morphological changes resembling post-infectious GN but with no clinical evidence to support an infectious etiology. Multiple treatment regimens were unable to control the disease. Symptoms were alleviated by rituximab but did not completely remit. Stable remission of the periodic fever and GN was finally achieved after anakinra therapy was initiated 18 months ago. Since then, the patient had several episodes of documented infection without high fever and nephritic kidney manifestations. His kidney function remained stable with normal serum creatinine.

Clinical and Histologic Resolution of Poststreptococcal Glomerulonephritis With Large Subendothelial Deposits and Kidney Failure

A 16-year-old male adolescent who had fallen and scratched his knee developed cold-like symptoms. Gross hematuria, oliguria, and peripheral edema appeared about 2 weeks after his fall. Tests showed hypocomplementemia, increased antistreptolysin O titers, and severe kidney failure with hematuria/proteinuria. Kidney biopsy showed endocapillary proliferative glomerulonephritis visible using light microscopy and deposits of complement C3 on capillary walls, detectable using immunofluorescence microscopy. Although these findings suggested that he had acute poststreptococcal glomerulonephritis (APSGN), electron microscopy failed to detect subepithelial humps, a feature typical of APSGN; instead, massive electron-dense deposits were visible in the subendothelial space. A second biopsy performed 3 months later showed mesangial cell proliferation without endocapillary proliferation using light microscopy and the disappearance of subendothelial electron-dense deposits in electron micrographs, suggesting that APSGN had resolved. Glomerular deposition of nephritis-associated plasmin receptor, a nephritogenic streptococcal antigen, was observed in the first biopsy specimen, but not the second. The patient required 4 hemodialysis treatments, and within 1 year of supportive therapy only, kidney function and urinalysis had normalized. This is an interesting case of APSGN presenting with acute kidney injury and atypical massive subendothelial deposits, but no subepithelial deposits on electron microscopy, a pattern resembling that in membranoproliferative glomerulonephritis type I.

Growth factor Midkine is involved in the pathogenesis of renal injury induced by protein overload containing endotoxin

Growth factor Midkine (MK), which expresses on endothelial cells and renal proximal tubules, has been implicated in inflammation-related kidney diseases such as ischemic reperfusion-induced tubulointerstitial injury and diabetic nephropathy. The biological actions of MK are elicited through its chemotactic activity and chemokine-driven inflammatory pathway. Post-infectious glomerulonephritis is caused by the deposition of immune complexes into glomeruli by infiltrating a number of inflammatory cells. Therefore, we investigated whether MK might be involved in the pathogenesis of acute glomerulonephritis. We induced endocapillary proliferative glomerulonephritis in 129/SV mice using intraperitoneal injections of a large amount of protein. In contrast to mice deficient in MK (Mdk (-/-)), Mdk (+/+) mice induced by protein overload demonstrated more diffuse cellular proliferation in the mesangial areas and capillary lumens, eventually leading to glomerular damage and tubulointerstitial injury. This pathological observation could be attributable to neutrophil infiltration through the chemotaxis and stimulation of the MK-macrophage inflammatory protein (MIP)-2 pathway, but appeared to be due to the MK-related immunoglobulin (Ig)G deposition and C3 activation. These findings are often seen in infectious-related glomerular injury. Furthermore, the profile of MK expression was strongly consistent with that of glomerular damage and tubulointersititial injury. This study might provide a new insight into understanding the deleterious role of MK in endocapillary proliferative glomerulonephritis induced by protein overload.

Proliferative glomerulonephritis with monoclonal IgG deposits secondary to chronic lymphocytic leukemia. Report of two cases

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a recently described entity that is only rarely associated with a hematological or lymphoproliferative malignancy. We describe the cases of two men with preexisting chronic lymphocytic leukemia (CLL) who developed endocapillary proliferative glomerulonephritis with nonorganized monoclonal IgG(1) deposits. One biopsy also showed CLL infiltration of the cortex. Both patients were treated with rituximab in addition to cyclophosphamide in one case and fludarabine in the other with significant improvement of their renal disease and CLL. This report provides additional evidence to support the use of rituximab in the therapy of CLL-associated PGNMID.

IgA-Dominant Postinfectious Glomerulonephritis: Not Peculiar to Staphylococcal Infection and Diabetic Patients

Background: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. Methods: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. Results: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1 mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p = 0.007). There were no significant differences in other clinical parameters and outcome between the two groups. Conclusions: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.

Role of acute tubular necrosis with blood cast during endocapillary proliferative glomerulonephritis.

Role of acute tubular necrosis with blood cast during endocapillary proliferative glomerulonephritis.

A case of adult periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome associated with endocapillary proliferative glomerulonephritis

PFAPA is an acronym for periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. This syndrome has been usually described in pediatric patients and it generally resolves spontaneously. The endocapillary proliferative glomerulonephritis (EPG) is a glomerular injury characterized by hypercellularity in glomerular lumen and is caused by post-infectious or autoimmune diseases. In this paper, we describe the case of a 35-year-old man affected by PFAPA and EPG. To our knowledge this association has never been reported in the literature before.

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.

Infective endocarditis associated with acute renal failure: Repeat renal biopsy and successful recovery

Infective endocarditis (IE) is a serious disease with a high associated mortality rate, particularly when complicated by acute renal failure (ARF). Although valve surgery and treatment with antibiotic agents are recommended, surgical options and the optimal therapy are not as yet well documented. Here, we report a rare case of IE in a young man with a history of intravenous drug abuse, who presented with high fever, bilateral thoracalgia, lower limb edema and renal dysfunction. After treatment with antibiotics, hemodialysis and anticoagulants, a tricuspid valve replacement surgery was performed on the patient. After surgery, his renal functions deteriorated and progressed to ARF. The first renal biopsy showed type II crescentic glomerulonephritis. After receiving continuous ambulatory peritoneal dialysis followed by administration of an angiotensin converting enzyme inhibitor and angiotensin receptor blockers, the patient's serum creatinine level decreased and the urine output increased gradually. In order to identify the renal turnover, we performed a second biopsy and found significant improvement in the pathological changes with endocapillary proliferative glomerulonephritis and fibrous crescents. Successful recovery of renal function was achieved 12 weeks after the initiation of therapy. Therefore, eradication of infection, tricuspid valve replacement and renal substitution therapy may be sufficient in some cases.

The Spectrum of Adult Postinfectious Glomerulonephritis in the New Millennium

Background. Postinfectious glomerulonephritis is rare in adults. The characteristics of the disease now differ from what were described decades ago. The goal of this study is to illustrate the clinicopathological spectrum of the disease in the modern era. Methods. Between July 2000 and June 2008, 20 adult cases of postinfectious glomerulonephritis were identified at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, microbiology, serology, morphology of renal biopsy, and clinical course. Results. There were 14 males and 6 females. The mean age was 61 years. All patients developed acute renal failure, and the majority (65%) required dialysis support during the disease course. Hypocomplementemia was present in 60% of patients. The most frequently identified infectious agent was Staphylococcus (60%). Histological characteristics showed two distinct patterns of glomerulonephritis: diffuse endocapillary proliferative glomerulonephritis (65%) and focal mesangial proliferative glomerulonephritis (35%). There were no significant differences in the clinical presentation and outcome between the two groups. However, glomerular neutrophil infiltration was more commonly present in diffuse endocapillary proliferative pattern (p = 0.017). The percentage of patients with focal mesangial proliferative pattern significantly increased over time (p < 0.001). At the last follow-up, 6 patients (30%) had died, 6 (30%) were in complete remission, 4 (20%) had partial remission with renal insufficiency, and 4 (20%) were on chronic dialysis. Conclusions. Our data suggested that Staphylococcus had become the leading pathogen in adult postinfectious glomerulonephritis over the past 10 years. Furthermore, atypical histological feature with focal mesangial proliferative pattern was increasingly identified over time. The prognosis was still guarded, carrying a considerable mortality rate and risk for developing chronic renal failure.