Clinical and histological features of patients with membranoproliferative glomerulonephritis classified by immunofluorescence findings / Características clínicas e histológicas de pacientes com glomerulonefrite membranoproliferativa classificados por achados de imunofluorescência

Abstract Background: New classification for membranoproliferative glomerulonephritis has been proposed in the literature. The aim of this study was to compare the clinical, biochemical, etiology and renal biopsy findings of these patients grouped by immunofluorescence as proposed by the new classification. Methods: Patients with renal biopsy-proven membranoproliferative glomerulonephritis unrelated to systemic lupus erythematosus, diagnosed between 1999 and 2014. The patients were divided according to immunofluorescence: Immunoglobulin positive group, C3 positive only and negative immunofluorescence group. Results: We evaluated 92 patients, the majority of which were in the immunoglobulin positive group. Infectious diseases, hepatitis C virus and schistosomiasis, were the most frequent etiology. A negative immunofluorescence group had more vascular involvement in renal biopsy compare with others groups. Conclusions: The only difference between the groups was higher vascular involvement in renal biopsy in negative immunofluorescence group. These new classification was satisfactory for the finding of etiology in one part of the cases.

Resumo Introdução: Uma nova classificação para glomerulonefrite membranoproliferativa foi proposta na literatura. O objetivo deste estudo foi comparar os achados clínicos, bioquímicos, etiológicos e da biópsia renal desses pacientes agrupados por imunofluorescência, conforme proposto pela nova classificação. Métodos: Pacientes com glomerulonefrite membranoproliferativa comprovada por biópsia renal, não relacionada ao lúpus eritematoso sistêmico, diagnosticados entre 1999 e 2014. Os pacientes foram divididos de acordo com a imunofluorescência: grupo positivo por imunoglobulina, grupo positivo por C3 apenas e grupo com imunofluorescência negativa. Resultados: avaliamos 92 pacientes, a maioria dos quais estava no grupo de imunoglobulina positiva. Doenças infecciosas, o vírus da hepatite C e a esquistossomose, foram as etiologias mais frequentes. Um grupo com imunofluorescência negativa apresentou maior comprometimento vascular na biópsia renal quando comparado com os outros grupos. Conclusões: a única diferença entre os grupos foi o maior envolvimento vascular na biópsia renal no grupo de imunofluorescência negativa. Esta nova classificação foi satisfatória para a descoberta de etiologia em uma parte dos casos.

Clinical and histological features of patients with membranoproliferative glomerulonephritis classified by immunofluorescence findings.

BACKGROUND: New classification for membranoproliferative glomerulonephritis has been proposed in the literature. The aim of this study was to compare the clinical, biochemical, etiology and renal biopsy findings of these patients grouped by immunofluorescence as proposed by the new classification. METHODS: Patients with renal biopsy-proven membranoproliferative glomerulonephritis unrelated to systemic lupus erythematosus, diagnosed between 1999 and 2014. The patients were divided according to immunofluorescence: Immunoglobulin positive group, C3 positive only and negative immunofluorescence group. RESULTS: We evaluated 92 patients, the majority of which were in the immunoglobulin positive group. Infectious diseases, hepatitis C virus and schistosomiasis, were the most frequent etiology. A negative immunofluorescence group had more vascular involvement in renal biopsy compare with others groups. CONCLUSIONS: The only difference between the groups was higher vascular involvement in renal biopsy in negative immunofluorescence group. These new classification was satisfactory for the finding of etiology in one part of the cases.

Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies.

An enhanced understanding of the role of complement in the pathogenesis of membranoproliferative glomerulonephritis has led to reclassification of the latter into immunoglobulin-mediated and non-immunoglobulin-mediated disease. The new classification schema resulted in improved diagnostic clinical algorithms, while it brought into light again the diseases, which are characterized by the presence of glomerular deposits, composed predominantly by C3, in the absence of significant amounts of immunoglobulins in renal biopsy, namely, C3 glomerulopathies (dense deposit disease and C3 glomerulonephritis). Despite the lack of randomized controlled trials following the advances in the understanding of the pathogenetic pathways involved in membranoproliferative glomerulonephritis, it is important that the new mechanistic approach has opened new roads for the exploration and discovery of targeted therapies.

Manifestations of Complement-Mediated and Immune Complex-Mediated Membranoproliferative Glomerulonephritis: A Comparative Consecutive Series.

PURPOSE: Membranoproliferative glomerulonephritis (MPGN) recently was reclassified to reflect the underlying cause as a complement-mediated and immune complex-mediated disease. This classification is based on renal biopsy immunofluorescence examination, making the former electron-microscopy classification obsolete. In this report, we describe related eye findings in patients with MPGN based on the new classification. DESIGN: Retrospective case series. PARTICIPANTS: All Mayo Clinic Rochester patients with pathology-confirmed complement- and immune complex-mediated MPGN who had available ophthalmology records from 1997 through 2014 were included in this study. METHODS: The medical and pathologic records of patients with MPGN and eye examination results were reviewed from years 1997 through 2014. MAIN OUTCOME MEASURES: The number of patients and the number of eyes with MPGN-related pathologic features were examined. Visual acuity also was considered. RESULTS: There were 23 patients with complement-mediated MPGN and available eye examination results. Of these, 9 patients (39%) and 17 eyes (37%) had retinal pathologic features that likely were related to the same underlying pathophysiologic process as their renal disease. Five patients (22%) and 6 eyes (13%) had significant vision loss. There were 23 patients with immune complex-mediated MPGN and available eye examination results. Only 2 (9%) of these patients (4 eyes) had retinal pathologic features that potentially could be related to the same underlying pathophysiologic process as their renal disease, and neither had vision loss. CONCLUSIONS: Retinal abnormalities are more prominent among patients with complement-mediated MPGN when compared with patients with immune complex-mediated MPGN. It is critical for ophthalmologists to recognize the updated MPGN classification system, and all patients with complement-mediated MPGN require screening eye examinations.

Clinicopathological features of membranoproliferative glomerulonephritis under a new classification.

BACKGROUND: A recent classification of membranoproliferative glomerulonephritis (MPGN) utilizes the presence of immunoglobulin and complements to simplify diagnosis and point towards disease etiology. Here, we evaluate a historic cohort of patients with idiopathic MPGN using the new classification system and correlate it with clinical outcome. METHODS: We identified 281 patients diagnosed with MPGN at Stanford from 2000 to 2012. Patients with hepatitis, systemic lupus erythematosis, lymphomas, and plasma cell dyscrasias were excluded. The clinicopathologic findings of the remaining 71 patients were further analyzed and differences between immunoglobulin dominant (IM) and complement dominant (CM) disease were evaluated. RESULTS: Using the new classification system, 51 subjects were characterized as CM MPGN and 20 as IM MPGN. In the CM MPGN group, there was a non-significant trend towards lower proteinuria but higher serum creatinine values. At biopsy, most subjects had less than 50% global sclerosis or cortical scarring. The majority of subjects in the CM MPGN group (41%) had C3 nephropathy while 60% of subjects in IM MPGN group had C3 dominant disease. Treatment and outcomes: During follow-up (median 2 years), 20 patients reached a clinical end point of dialysis or death. The mean creatinine was significantly higher while the baseline proteinuria also trended slightly higher. Prednisone use was statistically higher in the survivor group. CONCLUSIONS: Our study highlights the clinicopathological features of patients with biopsy proven MPGN with no known etiological factors and sheds some light on the incidence and outcomes of various categories of MPGN under the new criteria, including MPGN with "dominant C3" deposits, rapidly becoming a descriptive diagnosis.

Toward a working definition of C3 glomerulopathy by immunofluorescence.

Precise immunofluorescence criteria for C3 glomerulopathy remain to be defined. Here we tested hierarchical immunofluorescence criteria with varying stringency for C3 glomerulopathy in a cohort with dense deposit disease as the gold standard and then applied these criteria to analyze the incidence of C3 glomerulopathy in membranoproliferative glomerulonephritis (MPGN) types 1 and 3. Among 319 archived cases of primary MPGN types 1-3, immunofluorescence reports were retrospectively coded as glomerular deposits of the following: C3 only; C3 dominant with trace or 1+ immunoglobulin (Ig)M only; and C3 dominant and at least two orders of intensity stronger than any combination of IgG, IgM, IgA, and C1q. The most restrictive criteria of 'C3 only' captured only half of the cases with dense deposit disease (compared with 8% of type 1 and 10% of type 3). Adding the most liberal definition identified 88% of those with dense deposit disease (compared with 31% of type 1 and 39% of type 3). The unaccounted 12% had stronger intensity of Ig staining, but it never exceeded the intensity of C3. Among MPGN type 3, 90% of C3 glomerulopathy cases were the Strife and Anders variant. Repeat biopsies in C3 glomerulopathy revealed a change in immunofluorescence pattern in 10 of 23 biopsies. The prevalence of low serum C3 and/or low C4 did not significantly differ among the three immunofluorescence criteria. Thus, 'C3 only' is an impractical definition of C3 glomerulopathy, and we propose a definition of C3 dominant and at least two orders of magnitude more intense than any other immune reactant, which requires validation by alternative pathway evaluation. These criteria provide a framework for identifying patients most likely to benefit from investigations of alternative complement pathway dysregulation.

Re-evaluation of the classification system for membranoproliferative glomerulonephritis.

In recent years, significant advances have been made in understanding the pathogenesis and etiology of membranoproliferative glomerulonephritis (MPGN). A new classification system based on pathological immunofluorescence findings has been proposed to replace the traditional clinical classification system in order to better identify the underlying causes of MPGN and to provide guidance for more individualized treatment. We conducted a retrospective survey of the MPGN patients treated in our hospital from 2000 to 2012 and report here the validation of this new classification system in this cohort. A total of 34 patients were diagnosed with MPGN, including 25 males and 9 females. There were 3 cases of secondary MPGN, including 1 case due to monoclonal gammopathy of undetermined significance (MGUS) and 2 cases related to hepatitis B virus (HBV) infection. Clinical presentations included nephrotic syndrome (76.5%), microscopic hematuria (79.4%), hypocomplementemia (58.8%), renal insufficiency (82.4%), hypertension (100%), and peripheral edema (100%). All patients were treated with prednisone and immunosuppressive agents, mainly cyclophosphamide. During follow-up (median 6 months, range 3-47 months), 4 patients were lost to follow-up and 2 patients progressed to end-stage renal disease. In Western countries the main cause of secondary MPGN was hepatitis C virus or HBV infection, here however we report 2 cases related to HBV infection. MGUS-associated MPGN was less frequent in the Chinese cohort. Future studies should be designed to evaluate the association of the new classification system and clinical outcomes of MPGN.

Idiopathic membranoproliferative glomerulonephritis: does it exist?

When membranoproliferative glomerulonephritis (MPGN) was first delineated as a discrete clinico-pathological entity more than a half-century ago, most cases were regarded as idiopathic (or primary) in nature. Advances in analysis of pathogenetic mechanisms and etiologies underlying the lesion of MPGN have radically altered the prevalence of the truly idiopathic form of MPGN. In addition, MPGN as a category among renal biopsies showing glomerulonephritis has diminished over time. In the modern era, MPGN is mainly classified morphologically on the basis of immunoglobulin (Ig; monoclonal or polyclonal) and complement (C3 only or combined with Ig) deposition and secondarily on the basis of its appearance on ultra-structural examination. Idiopathic MPGN is a diagnosis of exclusion, at least in many adults and a portion of children, and a systematic approach to evaluation will often uncover a secondary cause, such as an infection, autoimmune disease, monoclonal gammopathy, neoplasia, complement dysregulation or a chronic thrombotic microangiopathy. Idiopathic MPGN remains an 'endangered species' after its separation from these known causes.

Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement.

BACKGROUND AND OBJECTIVES: dense deposit disease (DDD) is the prototypical membranoproliferative glomerulonephritis (MPGN), in which fluid-phase dysregulation of the alternative pathway (AP) of complement results in the accumulation of complement debris in the glomeruli, often producing an MPGN pattern of injury in the absence of immune complexes. A recently described entity referred to as GN with C3 deposition (GN-C3) bears many similarities to DDD. The purpose of this study was to evaluate AP function in cases of GN-C3. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five recent cases of MPGN with extensive C3 deposition were studied. Renal biopsy in one case exhibited the classic findings of DDD. Three cases showed GN-C3 in the absence of significant Ig deposition; however, the classic hallmark of DDD-dense deposits along the glomerular basement membranes and mesangium-was absent. The remaining case exhibited features of both DDD and GN-C3. RESULTS: Evidence of AP activation was demonstrable in all cases and included increased levels of soluble membrane attack complex (all cases), positive AP functional assays (four cases), and a positive hemolytic assay (one case). Autoantibodies were found to C3 convertase (two cases) and to factor H (one case). Factor H mutation screening identified the H402 allele (all cases) and a c.C2867T p.T956M missence mutation (one case). Laser microdissection and mass spectrometry of glomeruli of GN-C3 (two cases) showed a proteomic profile very similar to DDD. CONCLUSIONS: These studies implicate AP dysregulation in a spectrum of rare renal diseases that includes GN-C3 and DDD.

Variations in the complement regulatory genes factor H (CFH) and factor H related 5 (CFHR5) are associated with membranoproliferative glomerulonephritis type II (dense deposit disease).

INTRODUCTION: Membranoproliferative glomerulonephritis type II or dense deposit disease (MPGN II/DDD) causes chronic renal dysfunction that progresses to end stage renal disease in about half of patients within 10 years of diagnosis. Deficiency of and mutations in the complement factor H (CFH) gene are associated with the development of MPGN II/DDD, suggesting that dysregulation of the alternative pathway of the complement cascade is important in disease pathophysiology. SUBJECTS: Patients with MPGN II/DDD were studied to determine whether specific allele variants of CFH and CFHR5 segregate preferentially with the MPGN II/DDD disease phenotype. The control group was compromised of 131 people in whom age related macular degeneration had been excluded. RESULTS: Allele frequencies of four single nucleotide polymorphisms in CFH and three in CFHR5 were significantly different between MPGN II/DDD patients and controls. CONCLUSION: We have identified specific allele variants of CFH and CFHR5 associated with the MPGN II/DDD disease phenotype. While our data can be interpreted to further implicate complement in the pathogenesis of MPGN II/DDD, these associations could also be unrelated to disease pathophysiology. Functional studies are required to resolve this question.

Myeloid-related protein 8 expression on macrophages is a useful prognostic marker for renal dysfunction in children with MPGN type 1.

BACKGROUND: To clarify the role of subclasses of macrophages in chronic glomerulonephritis, we evaluated the relationship between myeloid-related protein 8 (MRP8) and MRP14 expression on macrophages and the progression of membranoproliferative glomerulonephritis (MPGN). METHODS: We enrolled 35 patients with MPGN type 1 who had a normal creatinine clearance at the time of their first renal biopsy and divided them into 2 groups based on clinical status at the time of their most recent examination: 12 patients with normal urine test results and 12 patients with minor urinary abnormalities at the latest observation (group 1) and 7 patients with persistent nephropathy and 4 patients with renal insufficiency (group 2). The first and second renal biopsy findings and MRP8 and MRP14 expression on macrophages were investigated in both groups. RESULTS: Mean scores for positive glomerular and interstitial MRP8 and CD68 staining at the time of the first and second biopsies were significantly higher in group 2 than group 1. At the time of the second biopsy, mean scores for interstitial CD68-positive (CD68 +) staining were higher in group 2 than group 1. Mean scores for glomerular and interstitial MRP8 + and CD68 + staining at the time of the first biopsy correlated with the chronicity index at the time of second biopsy in both groups. CONCLUSION: Results suggest that MRP8 expression on macrophages in glomeruli and interstitial lesions at the first biopsy can be a useful prognostic marker for renal dysfunction in children with MPGN type 1.

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.

Familial membranoproliferative glomerulonephritis type III.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a relatively uncommon cause of progressive renal disease characterized by immune complex deposition resulting in mesangial proliferation and endocapillary inflammation with capillary wall thickening and double contour formation. Although a familial linkage has been reported in MPGN type II disease and less often in type I disease, a familial linkage in type III disease has not been reported previously. METHODS: We identified a family in which MPGN type III developed in a living-related donor 12 years later and recurred in the renal allograft of his son, whose primary disease was MPGN type III. We screened the members of the extended family, looking for evidence of hematuria and proteinuria. Renal biopsy specimens exhibited the findings of subendothelial deposits, subepithelial deposits, and complex glomerular basement membrane changes with C3 but not IgG seen on immunofluorescence. RESULTS: Screening identified eight affected family members (six biopsy proven) over three generations. The condition is inherited in an apparent autosomal dominant fashion. CONCLUSION: This is the first description of familial MPGN type III. We hope that by studying the disease in this family group, we may learn more about the pathogenesis of the condition.

Quantitative analysis of the interstitial mast cells in idiopathic mesangiocapillary glomerulonephritis type I.

Fourteen renal biopsy specimens from patients with mesangiocapillary glomerulonephritis type I (MCGN-I) for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available were examined quantitatively. As a control 10 biopsy specimens of kidneys removed because of trauma were used. Morphometric investigations were performed by means of a computer image analysis system to evaluate whether mast cells have a role in tubulointerstitial fibrosis in MCGN-I and to examine the relationship between mast cells and interstitial alpha-smooth muscle actin (alpha-SMA) expression as well as interstitial infiltrates. The morphometric study revealed that the mean values of the interstitial tryptase positive cells, expression of alpha-SMA, interstitial volume, CD 68+, CD 45RB+, CD 43+ and CD 20+ cells were significantly increased in MCGN-I patients in comparison with control group. In MCGN-I group there were significant positive correlations between interstitial tryptase positive cells and interstitial expression of alpha-SMA, interstitial volume, serum creatinine as well as CD 43+ and CD 68+ cells. The correlations between interstitial tryptase positive cells and CD 45+, as well as CD 20+ cells did not reach statistical significance. In conclusion, our findings demonstrate that mast cells are one of the constitutive cell types in the interstitium in MCGN-I. Additionally, significant positive correlations between interstitial mast cell count and relative interstitial volume as well as serum creatinine concentration suggest the role of these cells in the development of interstitial fibrosis which may contribute to the renal deterioration in patients with MCGN-I.

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.

Nephrotic syndrome associated with diffuse mesangial hypercellularity: is it a heterogeneous disease entity?

Diffuse mesangial hypercellularity (DMH) is a rare primary mesangial proliferative glomerulonephritis associated with idiopathic nephrotic syndrome (INS). We conducted this study on 15 patients, including 5 patients with repeated specimens, with a follow-up of 0.9-17.5 years and evaluated the clinical course and pathological findings. Seven patients were male. Ten patients were under 14 years of age. All specimens had INS and were diagnosed morphologically with primary diffuse mesangial proliferative glomerulonephritis at initial biopsy; 4 were diagnosed with focal segmental glomerulosclerosis (FSGS) within 3 years by the second biopsy. The remaining 11 patients included 8 initial responders and 3 initial nonresponders to 8 weeks' steroid therapy and had the histologic variant of the minimal-change nephrotic syndrome (MCNS). Ten of the 11 patients had normal renal function during the investigation period. One patient with the MCNS variant who was refractory to steroid therapy developed end-stage renal disease (ESRD) within 6 years. Four patient with the histologic variant of FSGS included 1 initial responder, 2 late responders, and 1 steroid-refractory case. One patient with the FSGS variant developed ESRD within 4 years. The follow-up biopsies documented that the severity of mesangial hypercellularity was associated with the severity of proteinuria or hematuria. We conclude that DMH may be divided into heterogeneous disease entities, whereas morphologic changes in initial biopsies were similar. Each variant as well as the degree of DMH should be recognized routinely by follow-up biopsy, because they are prognostic indicators.

The nonspecificity of focal segmental glomerulosclerosis. The defining characteristics of primary focal glomerulosclerosis, mesangial proliferation, and minimal change.

We performed a detailed clinical review and pathologic analysis of the kidney biopsies of 134 children with nephrotic syndrome or asymptomatic proteinuria. This analysis challenges some of our concepts about the classification of conditions associated with these disorders. The presence of focal segmental sclerotic lesions does not define a unique disorder in childhood. Some children with such lesions will have unaffected glomeruli that are ultrastructurally completely normal. These patients, predominately black adolescents, present either with nephrotic syndrome or asymptomatic proteinuria. We classify this disorder as primary focal segmental glomerulosclerosis (FSGS) and have never found it to recur after transplantation. Most other children with FSGS have 1 of 2 specific glomerulopathies. Those with minimal change have generalized fusion of podocyte foot processes. Those with mesangial proliferation have similar foot process changes combined with mesangial expansion and proliferation and, frequently, thinning of the lamina densa and tubuloreticular inclusions. The presence of segmental lesions in these glomerulopathies appears to be nothing more than a marker of severity. Children with these glomerulopathies are generally younger white children, virtually all of whom have nephrotic syndrome. These disorders have a strong propensity to recur after transplantation. The presence of mesangial labeling of IgM or C1q has no significance in any of these 3 disorders. The classification of disorders associated with nephrotic syndrome or asymptomatic proteinuria must concentrate less on the presence or absence of focal sclerosis and more on the histologic appearance of the rest of the glomeruli.

[Mesangiocapillary glomerulonephritis]. / Mesangiocapillaris glomerulonephritis.

Mesangiocapillary glomerulonephritis (MCGN) accounting for 15 percent of adult glomerulopathy has not received proper attention in the Hungarian medical literature. The present study offers a detailed description of the procedures to be used for distinguishing its three types, which is only possible by histological, mainly electron microscopic examination of kidney biopsy samples. Type I represents subendothelial deposits; Type II is the "sausage-like" dense deposits localised on the lamina densa of the glomerular basal basement membrane; Type III is the mixed type. There is no significant difference in their clinical appearance. They occur most frequently as "coloured nephrosis" (the syndrome of nephrosis is associated with haematuria and/or hypertension). The course of the disease is characterised by periodicity, and in 50 percent of the cases kidney failure may develop. The therapy for MCGN has not been established. The administration of steroid, cyclophosphamide and anticoagulant can have a favourable effect.