Membranoproliferative glomerulonephritis, type II and partial lipodystrophy in an adult

Membranoproliferative glomerulonephritis, type II is commonly seen in patients with the rare disorder, partial lipodystrophy. This disease complex, although usually seen in the pediatric or young adult age group, should be considered in older patients with characteristic loss of facial fat and signs and symptoms of nephritis. A case of partial lipodystrophy with membranoproliferative glomerulonephritis, type II in an older patient demonstrates the characteristic ultrastructural renal findings.     

Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease

Twenty-seven patients presenting to the Royal Melbourne Hospital between 1968 and 1988 with mesangiocapillary glomerulonephritis type II with intramembranous dense deposits (dense-deposit disease, DDD) are analyzed. Patients were divided into two groups on the basis of whether renal function deteriorated (14 patients) or remained stable (13 patients). At presentation or during the course of the disease, heavy proteinuria, macroscopic hematuria, and high quantitative urinary red cell or white cell counts characterized patients with progressive disease. Patients with crescents on their initial renal biopsy or with large numbers of polymorphs in glomerular capillaries corresponding with sterile pyuria were more likely to have deterioration of renal function. The average time from onset of symptoms to development of end-stage renal disease was over 16 years. The patient's clinical course could not be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. Pregnancy did not affect the course of the disease. Six patients underwent renal transplantation and the disease recurred on renal biopsy in four. However, only two individuals lost renal allografts due to recurrent DDD.     

Membranoproliferative glomerulonephritis in a patient with Wilson's disease

Wilson's disease is an autosomal recessive disorder of hepatobiliary copper metabolism. Glomerular diseases can ensue during the course of Wilson's disease and membranous nephropathy is the eventual pathology in the majority of these cases. Membranoproliferative glomerulonephritis (MPGN) has rarely been reported in patients with Wilson's disease. Further, in this report, we present a patient with Wilson's disease who had developed MPGN during follow-up due to D-penicillamine therapy. This case is presented to draw attention to the rare association of Wilson's disease and MPGN and to discuss the possible underlying causes.     

Membranoproliferative glomerulonephritis associated with sickle cell disease in two siblings

The cases of two brothers with sickle-cell anemia complicated by the nephrotic syndrome and membranoproliferative glomerulonephritis are presented. The literature related to this infrequent association is reviewed and possible explanations for the occurrence of the latter in two brothers are discussed.     

Membranoproliferative glomerulonephritis in childhood: Factors affecting prognosis

Membranoproliferative glomerulonephritis (MPGN) is a distinctive form of chronic glomerulonephritis. We present the results of our 96 paediatric patients with MPGN, reporting the survival and factors affecting prognosis in these patients. There were 64 boys and 32 girls with an age range of 2–17 (mean 10.6±3.7) years. All patients initially received oral corticosteroid therapy; remission was achieved in 22.9%. The unresponsive 77.1% either received cyclophosphamide and/or pulse methylprednisolone; 25.4% and 50.0% of these patients entered complete remission, respectively. The overall 1-year renal survivals of the MPGN patients were 90.1%, 5-year and 10-year survival rates were 81.9% and 61%, respectively. At multivariate analysis the factors affecting renal prognosis were haematuria at presentation (p<0.05, risk factor 3.52), urinary protein/creatinine ratio (p<0.05, risk factor 1.06 per 1 unit) and low haemoglobin values (p<0.05, risk factor 1.43 for each 1 g/dl decrement). We suggest that more aggressive immunosuppressive therapy should be instituted in patients unresponsive to steroids and that the aforementioned risk factors are higher for the development of renal failure.     

Membranoproliferative glomerulonephritis type III: association of glomerular deposits with circulating nephritic factor-stabilized convertase

Deposits in the glomerular ultrastructure of 44 renal biopsy specimens from 21 patients with membranoproliferative glomerulonephritis (MPGN) type III have been compared with those in the ultrastructure of 34 biopsy specimens from 19 patients with MPGN type I. Previous studies have concluded that subepithelial deposits on the paramesangial portion of the glomerular basement membrane in MPGN types II and III are closely associated with circulating nephritic factor-stabilized convertase. In the present study, subendothelial deposits in MPGN type III were also found to be closely associated with nephritic factor; they were present in 14 of 26 (54%) biopsy specimens obtained during hypocomplementemia but in none of the 18 biopsy specimens obtained during normocomplementemia (P < 0.001). Subepithelial loop deposits in type III were also more frequent in biopsy specimens obtained during hypocomplementemia and are probably in some way also associated with circulating stabilized convertase. Taken together, the results of this and previous studies are compatible with the hypothesis that an excess of the C3b-dependent convertase in the circulation is basic to the pathogenesis of MPGN types II and III as well as of several other nephritides associated with factor H dysfunction. The half-life, structural complexity, and size of the convertases circulating in these nephritides increase in the following order: native convertase, convertase stabilized by the nephritic factor of the amplification loop (NFa), and convertase stabilized by nephritic factor of the terminal pathway (NFt). In the same order, the nephritides associated with these convertases more frequently manifest and have increasing amounts of glomerular deposit. This relationship of glomerular deposits with circulating convertase, however, is only circumstantial. There is no evidence that the convertase or a part thereof is a constituent of the deposits. The lesion that is the hallmark of MPGN type III is one in which interruptions of lamina densa are associated with subendothelial and subepithelial deposits, often confluent, and interspersed with multiple layers of new lamina densa-like material. This "type III lesion," which by implication is also associated with circulating nephritic factor, is the most persistent of the glomerular deposits. For reasons that are not yet clear, the type III lesion was absent in three patients who were severely hypocomplementemic, and the diagnosis of type III was made only after this lesion appeared in biopsy specimens obtained later. In MPGN type I, differing from type III, subendothelial deposits were present in 100% of biopsy specimens obtained during hypocomplementemia and in 47% of those obtained during normocomplementemia. Their persistence in type I may reflect rearrangement and condensation of the deposited material, shown by other investigators to be dependent on the presence of immunoglobulin G, which is largely absent from the deposits in type III. The comparison of deposits in types I and III indicates that relating the presence of subendothelial and paramesangial deposits to the C3 level at the time of biopsy can be helpful in distinguishing types I and III when the type III lesion is not present.     

Membranoproliferative glomerulonephritis type I in children: correlation of clinical features with pathologic subtypes

Renal biopsies from 33 patients with membranoproliferative glomerulonephritis (MPGN) type I were reviewed to identify pathologic subtypes of this disease and assess their correlation to clinical features. The patients were divided into two groups: group A included 16 patients in chronic or end-stage renal failure and group B 17 patients with no evidence of renal insufficiency. At presentation, a nephrotic or nephritic syndrome and azotemia were equally common in both groups. The incidence of hypertension was significantly increased in group A (P less than 0.05), while recurrent gross hematuria was more common in group B. Nephrotic syndrome was more common during the course of illness in group A. Three subtypes of MPGN type I were recognized, based on whether duplication of glomerular capillary basement membranes was focal segmental (FS; 9 cases), diffuse global (DG; 18 cases), or mixed segmental and global (6 cases). Eight of nine patients showing FS MPGN type I were in group B (p less than 0.05). In contrast, 11 of 18 patients with DG MPGN type I and 4 of 6 with a segmental and global pattern were in group A (P = not significant). Therefore, FS MPGN is a good predictor of a favorable clinical outcome, whereas the other two subtypes are not. This was confirmed by a 100% actuarial kidney survival for the nine patients with FS MPGN and a 50% kidney survival of 7.5 years for patients with the other two subtypes.     

Membranoproliferative glomerulonephritis type 1: comparison of natural history in children and adults.

Clinical, laboratory and pathological data on 46 patients (29 children and 17 adult) with Type 1 membranoproliferative glomerulonephritis (MPGN) were reviewed in order to compare the natural history of the disease in two age groups. The nephrotic syndrome was the most common presenting clinical feature in both age groups. Established renal failure at time of biopsy was seen in adult males only. All the adults males, but none of the women, were either dead or in renal failure after a mean duration of diseases of 17.7 months. In contrast 43% of the children (both sexes) were in renal failure after a mean duration of disease of 51.6 months. Statistical analysis disclosed that only up to 48 months was there a significant difference in survival between the two age groups (P less than .01). Beyond this time the difference was not statistically significant. The difference in behaviour of MPGN in the two age groups is similar to that observed in other glomerulonephropathies.     

电子致密物沉积病的临床及病理研究

目的：探讨电子致密物沉积病（DDD）的临床及病理特点。方法：通过5例DDD的临床及病理资料并结合文献复习,对其临床表现和组织形态学的多样性以及与治疗和预后的关系进行综合分析。结果：DDD占经肾活检证实的原发性肾小球疾病的0．2％,占膜增殖性肾炎的2％,5例中的3例临床表现为肾病综合征,组织学呈膜增生性肾炎（MPGN）,并伴有血C3降低,2例表现为慢性肾炎综合征,组织学1例呈MPGN伴有血C3降低;另1例呈系膜增生性病变,血C3正常,4例免疫荧光表现为以C3为主沿毛细血管壁呈颗粒状沉积,并有系膜区闭块状沉积,电镜下均可见电子致密物在肾小球毛细血管基底膜呈弥漫,均匀沉积,其中4例包曼囊及肾小管基底膜亦可见弥漫或节段电子致密物沉积,2例呈肾病综合征表现者对糖皮质激素治疗不敏感,结论：电子致密物沉积病是超微结构的诊断,其临床表现呈多样性,大量蛋白尿,严重高血压和较重的病理改变预示其预后不佳。     

Membranoproliferative glomerulonephritis (MPGN type I) and dense deposit disease (DDD) in children

A review of the histologic findings in 27 patients originally classified as having some form of membranoproliferative glomerulonephritis (MPGN) revealed 13 with MPGN Type I and 14 with dense deposit disease (DDD). In all 14 cases where electron microscopy was performed, the histologic diagnosis was confirmed. In nine cases the diagnosis of DDD was easily made in histologic sections on the basis of ribbon-like, brightly PAS positive thickening of the GBM, without "splitting" and with relatively slight mesangial proliferation. However, in five cases the picture closely resembled MPGN Type I, with hypercellularity, "splitting" and only focal ribbon-like thickening of the GBM, which required oil immersion for recognition. There was no correlation between the serum C3 levels and the morphologic diagnosis: nine (4 MPGN Type I, 5DDD) had persistently low C3 levels, two (1 MPGN Tye I, 1DDD) were normocomplementemic, and in 16, the C3 levels varied. C3 levels increased with time in nearly all patients. The clinical course was similar in patients with MPGN Type I and DDD. Significant correlations between the rate of development of renal failure and sex, age of onset, nephrotic syndrome or therapy could not be made. The five year survival rate was 87%; 12 developed renal insufficiency by five years. Although morphologically distinct, these findings suggest that DDD is clinically indistinguishable from MPGN Type I.     

Regression of membranoproliferative glomerulonephritis type II (dense deposit disease): observations in six children

Six children with membranoproliferative glomerulonephritis Type II (MPGN II-dense deposit disease), who were followed an average of 14 years (3.5 to 22 years) and treated continuously with an alternate-day prednisone regimen, have been studied by successive renal biopsies over intervals of 2 to 14 years of disease. All have shown significant reduction in mesangial proliferation and improvement of capillary lumen patency. A change in position of the deposits, from the lamina densa to the lamina rara interna, was demonstrated ultrastructurally in four of the patients, accompanied by reduction in prevalence of deposit in three. This loss of dense deposits, characterized as a process of "dropping off," was complete in the free capillary walls of two of the patients.