Progress of C3 glomerulopathy / 国际儿科学杂志

C3 glomerulopathy is a rare disease of glomeruli mediated by abnormal activation of alternative complement pathway secondary to congenital genetic defects and acquired autoantibodies.Renal biopsy is the gold standard for diagnosing C3 glomerulopathy.C3 glomerulopathy encompasses both dense deposit disease and C3 glomerulonephritis.The main glomerular immunofluorescence staining is C3, with few or without immunoglobulins deposition, which is the obvious pathological feature.The clinical manifestations of C3 glomerulopathy are usually various, with limited detection methods and therapies and poor prognosis.This article mainly reviews the progress of C3 glomerulopathy in recent years, in order to improve clinical understanding of C3 glomerulopathy, and choose individualized therapy.

Pathology of C3 Glomerulopathy

C3 glomerulopathy is a renal disorder involving dysregulation of alternative pathway complement activation. In most instances, a membranoproliferative pattern of glomerular injury with a prevalence of C3 deposition is observed by immunofluorescence microscopy. Dense deposit disease (DDD) and C3 glomerulonephritis (C3GN) are subclasses of C3 glomerulopathy that are distinguishable by electron microscopy. Highly electron-dense transformation of glomerular basement membrane is characteristic of DDD. C3GN should be differentiated from post-infectious glomerulonephritis and other immune complex-mediated glomerulonephritides showing C3 deposits.

Clinical and pathological characteristics of children with C3 glomerulopathy / 中华实用儿科临床杂志

Objective To investigate the clinicopathological features and treatment of children with C3 glomerulopathy (C3 G).Methods Seven children diagnosed as C3 G by clinical and pathological characteristics were enrolled in this study.The clinicopathological data and the prognosis were analyzed.Results Of the 7 cases,4 cases were female and 3 cases were male,with the mean age of (7.7-± 3.1) years old (1.5-10.4 years old) at onset,the duration from onset to renal biopsy was (3.4 ± 2.4) months (1-6 months) and 1 of them had a second renal biopsy 4.2 years later,and mean age was (8.4 ± 3.6) years old (1.8-13.3 years old) on diagnosis.Clinical features:among the 7 patients,6 cases had hematuria,among them 1 case had gross hematuria and 5 cases had microscopic hematuria;6 cases had low level of serum complement C3,5 cases had heavy proteinuria and low serum albumin,and anemia was observed in 2 cases respectively.Five cases had complement factor H and H factor antibody by examination,and 1 of them had low serum factor H,but none of them had serum antibody to factor H.Four cases had genetic evaluation,and only 1 case revealed risk variants in the C3 gene(R304R,T612T,V807V,A915A,P1632P)and CFH gene(p.H402Y,p.E936D).Clinically,4 cases were diagnosed as nephrotic syndrome of nephritis type,2 cases were diagnosed as nephritic syndrome,and 1 case was diagnosed as nephrotic syndrome of simple type.Immunofluorescence study showed that all the cases had intense deposition of C3,and 6 cases were accompanied by the deposition of immunoglobulin.Under light microscopy,3 cases showed the feature of membrane proliferative glomemlonephritis,2 cases with endocapillary prolifera-tive glomerulonephritis,1 case with mesangial proliferative glomerulonephritis,and 1 case with endoeapillary proliferative IgA nephropathy.Under electron microscopy,3 cases who had typical ribbon-like dense deposits in glomerular basement membrane were of dense deposit disease,and the rest were C3 glomerulonephritis.All patients had steroid and immune inhibitor treatment,and during the follow-up stage of (2.6 ± 1.8) years(1.1-5.6 years),4 cases showed normal urinalysis,2 cases had microproteinurine and microscopic hematuria,and 1 case had urinary protein ± to + + and microscopic hematuria.Conclusions C3G has variety of pathological-clinical manifestation.Interpretation of individual cases depends on integration of information from the biopsy together with clinical,serological,and genetic features.Patients with steroid and immune inhibitor treatment had some clinical improvement of their urinalysis.

Progress of C3 glomerulopathy / 中国小儿急救医学

C3 glomerulopathy is a group of diseases with immunofluorescence staining C3 along the glomerular capillary loops deposition,may be accompanied by other immunoglobulin deposition,but C3 sedi-mentary classic way was more than other immunoglobulin and complement activation ingredients ( such as C1q,C4). C3 glomerulopathy is a group of primary glomerular disease and relatively rare. This article mainly reviewed the pathological characteristic of C3 glomerulopathy,clinical manifestation,diagnosis and treatment, in order to improve clinical understanding of C3 glomerulopathy.

C3 glomerulopathy: Advances in diagnosis and treatment / 第二军医大学学报

C3 glomerulopathy is a recently defined disease category comprising several rare types of glomerulonephritis (GN), including dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and CFHRS nephropathy. These disorders share a common etiology involving dysregulation of the complement alternative pathway (AP), with genetic defects and/ or autoantibodies seen in a proportion of patients. Currently no consistently effective therapy has been found for C3 glomerulopathy; clinical evaluation of agents targeting specific components of the complement system is undergoing. The appropriate timing and duration of proposed therapies need to be further explored. This review focuses on the clinical and histological features, complement tests and treatments of C3 glomerulopathy.

Clinical and pathological features of dense deposit disease in children / 临床儿科杂志

10.3969/j.issn.1000-3606.2013.06.020

Dense Deposit Disease in Korean Children: A Multicenter Clinicopathologic Study

The purpose of this study was to investigate the clinical, laboratory, and pathologic characteristics of dense deposit disease (DDD) in Korean children and to determine whether these characteristics differ between Korean and American children with DDD. In 2010, we sent a structured protocol about DDD to pediatric nephrologists throughout Korea. The data collected were compared with previously published data on 14 American children with DDD. Korean children had lower 24-hr urine protein excretion and higher serum albumin levels than American children. The light microscopic findings revealed that a higher percentage of Korean children had membranoproliferative glomerulonephritis patterns (Korean, 77.8%; American, 28.6%, P = 0.036), whereas a higher percentage of American children had crescents (Korean, 0%; American, 78.6%, P < 0.001). The findings from the electron microscopy revealed that Korean children were more likely to have segmental electron dense deposits in the lamina densa of the glomerular basement membrane (Korean, 100%; American, 28.6%, P = 0.002); mesangial deposit was more frequent in American children (Korean, 66.7%; American, 100%, P = 0.047). The histological findings revealed that Korean children with DDD were more likely to show membranoproliferative glomerulonephritis patterns than American children. The degree of proteinuria and hypoalbuminemia was milder in Korean children than American children.

Development of IgA Nephropathy after Clinical Remission of Dense Deposit Disease / 대한신장학회지

Dense deposit disease (DDD) is a rare primary glomerulonephritis characterized by continuous band- like intramembranous dense deposits detectable on electron microscopy. We describe a case of DDD with sequential mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, minor glomerular alterations, and a second round of mesangial proliferative glomerulonephritis during a 13-year period. Electron dense deposits were typical of DDD in the first and second biopsies taken one year apart. However, deposits dissolved and the glomerular cellularity and basement membrane normalized with clinical remission, which was achieved by a course of immunosuppressive therapy lasting seven years. The fourth biopsy was performed due to recurrence of microscopic hematuria and showed predominant mesangial IgA deposits without glomerular capillary alteration, which was interpreted as development of IgA nephropathy after remission of DDD or coexistence with nearly healed DDD in this patient.

Two Cases of Type II Membranoproliferative Glomerulonephritis / 대한신장학회잡지

The term type II membranoproliferarive glomerulonephritis (MPGN) refers to the histopathologic entity characterized by dense intramembranous deposits. It have a variable clincal courses, frequently occurs in older children and young adult. In comparison with The western, the idiopathic membranoproliferative glomerulonephritis (MPGN) has a lower frequency than secondary MPGN. Especially, of the idiopathic MPGN, the frequency of type 2 MPGN, so called dense deposit disease, is very rare in Korea. We are reporting two cases of type II MPGN, which was proven by renal biopsy. The clinical manifestations were recurrent gross hematuria in one patient and persistent nephrotic-ranged proteinuria in the other patient. The biopsy findings are characterized by diffuse wall thickening of capillary walls and focal proliferation of mesangial cell in light microscopy, and by capillary wall and granular basement membrane staining of C3 in immunofluorescence microscopy, and an irregular fusiform swelling of the lamina densa which resulting in a further thickening of basement of basement membrane in electron microscopy. Our two patients were treated conservatively without using steroid or immunosuppressive agents. One patient who had followed-up for 7 years after diagnosis remain stable in renal function, and the other patient who had followed-up for 4 years after diagnosis showed persistent nephrotic-range proteinuria.

Two Cases of Type II Membranoproliferative Glomerulonephritis / 대한신장학회잡지

The term type II membranoproliferarive glomerulonephritis (MPGN) refers to the histopathologic entity characterized by dense intramembranous deposits. It have a variable clincal courses, frequently occurs in older children and young adult. In comparison with The western, the idiopathic membranoproliferative glomerulonephritis (MPGN) has a lower frequency than secondary MPGN. Especially, of the idiopathic MPGN, the frequency of type 2 MPGN, so called dense deposit disease, is very rare in Korea. We are reporting two cases of type II MPGN, which was proven by renal biopsy. The clinical manifestations were recurrent gross hematuria in one patient and persistent nephrotic-ranged proteinuria in the other patient. The biopsy findings are characterized by diffuse wall thickening of capillary walls and focal proliferation of mesangial cell in light microscopy, and by capillary wall and granular basement membrane staining of C3 in immunofluorescence microscopy, and an irregular fusiform swelling of the lamina densa which resulting in a further thickening of basement of basement membrane in electron microscopy. Our two patients were treated conservatively without using steroid or immunosuppressive agents. One patient who had followed-up for 7 years after diagnosis remain stable in renal function, and the other patient who had followed-up for 4 years after diagnosis showed persistent nephrotic-range proteinuria.

A Case of Membranoproliferative Glomerulonephritis Type II (Dense-Deposit Disease)

Membranoproliferative glomerulonephritis type II(MPGN II), also called dense deposit disease, was first described by Berger and Galle in 1963. The diagnosis of MPGN II is based on electron-microscopic finding of an intensely electron-dense substance which replaces the lamina densa of the glomerular basement membrane. Although the etiology and pathogenesis of MPGN II are unknown, it frequently progresses to end-stage renal failure. Typically in MPGN II, hypocomplementemia due to activation of the alternative complement pathway is present. In addition, the association of MPGN II with partial lipodystrophy and complement abnormalities is well documented. The relationship between these associated features and the patient's renal functional outcome is not clear. With respect to the therapy for MPGN II, an alternate-day prednisolone regimen was shown to be effective. Various treatment modalities, including immunosuppression with corticosteroids, cytotoxic drugs and cyclosporin A, anticoagulants and antiplatelet therapies are used, either alone or in combination, with varying degrees of success. The purpose of this paper is to present a case of MPGN II from a 7 years old girl with paroxysmal supraventricular tachycardia(PSVT).

A Case of Membranoproliferative Glomerulonephritis Type II (Dense-Deposit Disease)

Membranoproliferative glomerulonephritis type II(MPGN II), also called dense deposit disease, was first described by Berger and Galle in 1963. The diagnosis of MPGN II is based on electron-microscopic finding of an intensely electron-dense substance which replaces the lamina densa of the glomerular basement membrane. Although the etiology and pathogenesis of MPGN II are unknown, it frequently progresses to end-stage renal failure. Typically in MPGN II, hypocomplementemia due to activation of the alternative complement pathway is present. In addition, the association of MPGN II with partial lipodystrophy and complement abnormalities is well documented. The relationship between these associated features and the patient's renal functional outcome is not clear. With respect to the therapy for MPGN II, an alternate-day prednisolone regimen was shown to be effective. Various treatment modalities, including immunosuppression with corticosteroids, cytotoxic drugs and cyclosporin A, anticoagulants and antiplatelet therapies are used, either alone or in combination, with varying degrees of success. The purpose of this paper is to present a case of MPGN II from a 7 years old girl with paroxysmal supraventricular tachycardia(PSVT).

A Case of Membranoproliferative Glomerulonephritis Type II: Dense Deposit Disease, DDD

Type II membranoproliferative glomerulonephritis (Dense deposit disease ) is an acquired primary glomerular disease characterized by electron microscopic evidence of a continuous dense membrane deposition replacing the lamina densa. It is a subtype of idiopathic membra- noproliferative glomrulonephritis, and was described as a separate entity by Berger and Galle in 1963. It frequently occurs in older chilren and young adults and the clinical course is variable, but is generally progressive. The presenting feature is nephrotic syndrome in many patients, and proteinuria and hematuria are also seen frequently. The purpose of this paper is to present a case of DDD (Dense deposit disease) from a 10 year old boy who was diagnosed as a acute poststreptococcal glomurulonephritis with protenuria, hematuria, and facial edema by renal biopsy 4 years ago.