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Bogdanovic RM, Dimitrijevic JZ, Nikolic VN, Ognjanovic MV, Rodic BD, Slavkovic BV: Membranoproliferative glomerulonephritis in two siblings: report and literature review. Pediatr Nephrol 2000 May;14(5):400-5. Institute of Mother and Child Health of Serbia, Belgrade, Yugoslavia. maloun@eunet.yu There is evidence of a genetic basis in some cases of idiopathic membranoproliferative glomerulonephritis (MPGN) types I and III, particularly those occurring in families. The clinical and morphological features and disease course in two siblings with MPGN are described. In the male sibling, both clinical and morphological features as well as serum complement profile suggested type I MPGN; electron microscopy appearance in the female sibling was consistent with type III MPGN. Both patients had treatment-resistant nephrotic syndrome which evolved into renal insufficiency in the girl. No hereditary complement deficiencies were found in siblings or their parents. Both children exhibited HLA-A24; -B27, w4; -DR11, 52; -DQ3 antigens. Between 1981 and 1996, 18 patients from eight families with unequivocal diagnosis of MPGN I or III had been described. The mode of inheritance appeared to be autosomal dominant or X-linked in four of these families. In 11 patients, including our 2, in whom HLA typing was performed, eight had the HLA-A2 antigen. Similarities and discrepancies regarding clinical and morphological features and outcomes were evident in these intrafamilial cases, suggesting either a similar genetic background or a multigenic origin of MPGN. The familial occurrence of the MPGN, highlighted by our report, supports the concept that genetically determined factors may be involved in the pathogenesis of the disease. |
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Schena FP: Primary glomerulonephritides with nephrotic syndrome. Limitations of therapy in adult patients. J Nephrol 1999 Jul-Aug;12 Suppl 2:S125-30. Department of Emergency and Organ Transplant, University of Bari, Policlinico, Italy. fp.schena@nephro.uniba.it Thirty years of clinical studies have shown that a correct therapeutic approach to human glomerulonephritides with nephrotic syndrome requests the evaluation of three important parameters such as renal biopsy, long monitoring of daily proteinuria and renal function. In addition, age and clinical manifestations should be considered. Corticosteroids, alkylating agents (cyclophosphamide, chlorambucil) and purine analogues are currently used in the treatment of primary glomerulonephritis (minimal-change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous (MGN) and membranoproliferative glomerulonephritis (MPGN)), however results are different. Patients with nephrotic syndrome in MCD when treated with corticosteroids and/or cytotoxic drugs have complete or partial remission in a more than 90% of cases. On the contrary, nephrotic FSGS remits completely or partially only in 50% of treated cases when a more aggressive and prolonged immunosuppressive therapy is carried out. Data from clinical trials in MGN patients are controversial, however it is evident that a greater percentage of patients with stage 1 and stage 2 renal lesions benefit from corticosteroids in association with immunosuppressive drugs. Finally, no encouraging data have been obtained by clinically controlled trials in patients with MPGN. Future perspectives suggest the use of other drugs such as receptor blockade of cytokines and growth factors, administration of cytokine antagonists, intracellular signalling blockade and gene therapy with antisense oligonucleotides. Unfortunately, until specific therapies become available, we have to use unspecific or only symptomatic therapy. |
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Braun MC, West CD, Strife CF: Differences between membranoproliferative glomerulonephritis types I and III in long-term response to an alternate-day prednisone regimen. Am J Kidney Dis 1999 Dec;34(6):1022-32. Children's Hospital Research Foundation, Cincinnati, OH 45229-3039, USA. Membranoproliferative glomerulonephritis (MPGN) is classified as type I, II, or III based on ultrastructural alterations in the glomerular basement membrane. Whereas type II has long been recognized as clinically and pathologically unique, types I and III are often difficult to distinguish and have not been separated in most clinical studies. We compared the course and long-term outcome of patients with types I and III MPGN followed up at this institution since 1960. During this period, 21 patients with type I and 25 patients with type III were followed up for a minimum of 5 years. Patients with types I and III MPGN did not differ in age at apparent onset, age at diagnosis, or interval from apparent onset of symptoms to diagnosis (biopsy). They had similar initial serum C3 and serum albumin levels. Patients with type I had a significantly lower initial mean estimated glomerular filtration rate (GFR(est)) compared with those with type III (99.1 +/- 35.9 versus 131.6 +/- 36. 1 mL/min/1.73 m(2); P < 0.01). Type and duration of therapy, length of follow-up, and frequency of complications of therapy did not differ between groups. There was, however, a significant difference in duration of hypocomplementemia. After 1 year of an alternate-day prednisone regimen, 90% of the type I patients normalized their serum C3 levels compared with less than 50% of type III patients (P < 0.01). After 3 years of therapy, only 5% of type I patients were hypocomplementemic compared with 33% of type III patients (P < 0.02). In addition, disease relapse occurred in six type III patients (24%) compared with no type I patients. At last follow-up, type I patients had a slight improvement in mean GFR(est) (+6.3 +/- 48.4 mL/min/1.73 m(2)), whereas type III patients had a 25% decrease in mean GFR(est) (-34.8 +/- 47.6 mL/min/1.73 m(2); P < 0.01). Residual urinary abnormalities were significantly more frequent in patients with type III than type I MPGN. Hematuria persisted in 72% versus 38% (P < 0.05) and proteinuria in 28% versus 0% (P < 0.01) of those with types III and I, respectively. These results give clear evidence of significant differences in the clinical progression of the two types and their response to the alternate-day prednisone regimen. Whereas the outcome of patients with type I MPGN treated with alternate-day prednisone was generally good, similarly treated patients with type III experienced significant reductions in renal function, slower improvement in serum C3 levels, more persistent urinary abnormalities, and more frequent relapses.
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Hariharan S, Adams MB, Brennan DC, Davis CL, First MR, Johnson CP, Ouseph R, Peddi VR, Pelz CJ, Roza AM, Vincenti F, George V: Recurrent and de novo glomerular disease after renal transplantation: a report from Renal Allograft Disease Registry (RADR). Transplantation 1999 Sep 15;68(5):635-41. Department of Nephrology, Medical College of Wisconsin, Milwaukee 53226, USA. hari@mcw.edu INTRODUCTION: Short-term and long-term results of renal transplantation have improved over the past 15 years. However, there has been no change in the prevalence of recurrent and de novo diseases. A retrospective study was initiated through the Renal Allograft Disease Registry, to evaluate the prevalence and impact of recurrent and de novo diseases after transplantation. MATERIALS AND METHODS: From October 1987 to December 1996, a total of 4913 renal transplants were performed on adults at the Medical College of Wisconsin, University of Cincinnati, University of California at San Francisco, University of Louisville, University of Washington, Seattle, and Washington University School of Medicine. The patients were followed for a minimum of 1 year. A total of 167 (3.4%) cases of recurrent and de novo disease were diagnosed by renal biopsy. These patients were compared with other patients who did not have recurrent and de novo disease (n=4746). There were more men (67.7% vs. 59.8%, P<0.035) and a higher number of re-transplants (17% vs. 11.5%, P<0.005) in the recurrent and de novo disease group. There was no difference in the rate of recurrent and de novo disease according to the transplant type (living related donor vs. cadaver, P=NS). Other demographic findings were not significantly different. Common forms of glomerulonephritis seen were focal segmental glomerulosclerosis (FSGS), 57; immunoglobulin A nephritis, 22; membranoproliferative glomerulonephritis (GN), 18; and membranous nephropathy, 16. Other diagnoses include: diabetic nephropathy, 19; immune complex GN, 12; crescentic GN (vasculitis), 6; hemolytic uremic syndrome-thrombotic thrombocytopenic purpura (HUS/TTP), 8; systemic lupus erythematosus, 3; Anti-glomerular basement membrane disease, 2; oxalosis, 2; and miscellaneous, 2. The diagnosis of recurrent and de novo disease was made after a mean period of 678 days after the transplant. During the follow-up period, there were significantly more graft failures in the recurrent disease group, 55% vs. 25%, P<0.001. The actuarial 1-, 2-, 3-, 4, and 5-year kidney survival rates for patients with recurrent and de novo disease was 86.5%, 78.5%, 65%, 47.7%, and 39.8%. The corresponding survival rates for patients without recurrent and de novo disease were 85.2%, 81.2%, 76.5%, 72%, and 67.6%, respectively (Log-rank test, P<0.0001). The median kidney survival rate for patients with and without recurrent and de novo disease was 1360 vs. 3382 days (P<0.0001). Multivariate analysis using the Cox proportional hazard model for graft failure was performed to identify various risk factors. Cadaveric transplants, prolonged cold ischemia time, elevated panel reactive antibody, and recurrent disease were identified as risk factors for allograft failure. The relative risk (95% confidence interval) for graft failure because of recurrent and de novo disease was 1.9 (1.57-2.40), P<0.0001. The relative risk for graft failure because of posttransplant FSGS was 2.25 (1.6-3.1), P<0.0001, for membranoprolifera. tive glomerulonephritis was 2.37 (1.3-4.2), P<0.003, and for HUS/TTP was 5.36 (2.2-12.9), P<0.0002. There was higher graft failure (64.9%) and shorter half-life (1244 days) in patients with recurrent FSGS. CONCLUSION: In conclusion, recurrent and de novo disease are associated with poorer long-term survival, and the relative risk of allograft loss is double. Significant impact on graft survival was seen with recurrent and de novo FSGS, membranoproliferative glomerulonephritis, and HUS/TTP. |
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Bogdanovic RM, Dimitrjevic JZ, Nikolic VN, Ognjanovic MV, Rodic BD, Slavkovic BV : [Familial membranoproliferative glomerulonephritis]. Srp Arh Celok Lek 1999 May-Jun;127(5-6):163-71. Institute of Mother and Child Health of Serbia, Belgrade. [Article in Serbo-Croatian (Cyrillic)] INTRODUCTION: Idiopathic membranoproliferative (mesangiocapillary) glomerulonephritis (MPGN) is a chronic, often progressive renal disease with variable clinical expression divided into three distinct morphological formes, now designated types I, II, and III, on the basis of immunofluorescent (IF) and ultrastructural appearances and complement profiles [1-5]. Several lines of evidences suggest a genetic basis for at least some cases of MPGN I and III. The extended haplotypes HLA-B8, DR3, SCO1, GLO2 were found to constitute 13% of the disease-associated haplotypes and 1% of control hyplotypes [8]. Significantly high percentage of those with MPGN I and III have inherited defects of the complement system [9]. Additional evidence for genetic factors is the rarity of the disease in blacks [10] and examples of MPGN occurring in families. The disease has been reported in siblings as well as in families with affected members spanning more than one generation [11-16]. Here we describe clinical and morphological features in two siblings affected by MPGN and present complement and HLA typing studies done in patients and their parents. A review of familial MPGN I and III cases reported between 1981 and 1996 is made, and genetic susceptibility factors for MPGN are discussed. SUBJECTS AND METHODS: Between 1976 and 1996 diagnosis of idiopathic MPGN was made in 24 patients, aged 516.5 years. The diagnosis was established after excluding systemic, liver and infectious disorders and malignant neoplasms. The MPGN type was confirmed by light microscopy, IF and electron microscopy studies of the renal biopsy tissues processed by standard techniques. One family with two siblings having MPGN was identified in our series. This family was examined for the presence of renal disease and an inherited complement defect. Laboratory evaluations of the patients and parents included complete urinalysis, serum protein, albumin, urea, creatinine and cholesterol levels and glomerular filtration rate (GFR) estimation. ANA, rheumatoid factors, cryoglobulins, immune complexes, HBV antigens and antibodies and anti-HCV antibodies were also determined. Haemolytic tests for CHSO (classical and alternative pathways) were carried out using standard techniques. The measurement of the various complement factors was carried out using a radial immunodiffusion technique with monospecific antisera (CIq, C2, C4, C3, C5, B, H). HLA-A, B, DR and DQ haplotypes were determined by microcytotoxicity assay of peripheral blood lymphocytes. RESULTS: Patient 1 (SC, male). Renal disease presented at the age of his five years with nephrotic syndrome resistant to corticosteroid treatment. Morphological features and serum complement profile suggested type I MPGN. Treatment consisted of alternate-day prednisone, followed by cyclosporine and then by cyclophosphamide. At the end of the follow-up lasting 5.5 years he had only moderate proteinuria. Patient 2 (MC, female). Proteinuria was revealed at the age of 3 years becoming progressive and leading to the nephrotic syndrome resistant to corticosteroids at the age of 6 years. Electronmicroscopy features were consistent with type III MPGN, although serum C3 and C4 levels remained normal all the time. The same treatment as in her brother was given but she remained persistently nephrotic and anaemic; hypertension developed when she was 6 years old and her renal function became to declaine at the age of 7.5 years. Detailed family studies failed to reveal any evidence of complement deficiencies or secondary cause of MPGN. Siblings had in common HLA-A24, B27, Bw4, DRI1, DRS2, and DQ3 antigens. DISCUSSION: In our patients clinical and morphological features are very similar and are consistent with diagnosis of MPGN, i.e. probably type I in the boy and type III in the girl. Although some extended haplotypes HLA-B8, DR3, SCO1, GLO2, were significantly more frequent (13%) than in controls (1%), and the patients with MPGN having this extended haplotype. |
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Andresdottir MB, Assmann KJ, Koene RA, Wetzels JF: Immunohistological and ultrastructural differences between recurrent type I membranoproliferative glomerulonephritis and chronic transplant glomerulopathy. Am J Kidney Dis 1998 Oct;32(4):582-8. Department of Pathology, University Hospital Nijmegen, The Netherlands. m.andresdottir@nefro.azn.nl In renal transplant recipients with type I membranoproliferative glomerulonephritis (MPGN), the posttransplantation course can be complicated by a recurrence of the original disease. However, it is well known that a recurrence of type I MPGN and chronic transplant glomerulopathy (CTG) cannot easily be distinguished. It has been suggested that the two entities can be differentiated by using electron microscopy (EM) and immunofluorescence (IF) techniques. However, studies are lacking that compare biopsy specimens from patients with either a recurrence of type I MPGN or CTG. We have studied renal biopsy specimens from 10 patients with CTG and compared the ultrastructural and IF findings with biopsy specimens from 12 patients with a possible recurrence of type I MPGN. All the patients with CTG showed an electron-lucent zone of finely flocculent material in the subendothelial space, whereas all patients with a recurrence of type I MPGN showed subendothelial electron-dense deposits on EM. On IF, all patients with CTG showed Immunoglobulin M (IgM) with greater intensity than C3. For the patients with recurrent type I MPGN, the opposite was true. Eleven specimens showed C3 deposits with greater intensity than IgM, and in one patient, C3 and IgM were found in equal intensity. In conclusion, when IF and EM studies are available, CTG and recurrence of type I MPGN can reliably be distinguished. |
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Muramatsu T, Hora K, Ako S, Tachibana N, Hora K, Tanaka E. Hepatol. The role of hepatitis C virus infection in glomerulopathy. Res. 2000 Nov 1;18(3):190-202. Second Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Japan The characteristics and prevalence of hepatitis C virus (HCV)-associated glomerulopathy remain to be determined. To analyze the relationship between HCV infection and glomerulopathy, we enrolled three groups of individuals or patients. The first group consisted of 7776 individuals who were seen for routine checkups. The second group consisted of 86 patients with chronic hepatitis C, 40 patients with chronic hepatitis B, and 51 patients with non-viral liver diseases. The third group consisted of nine patients with HCV association glomerulopathy who underwent renal biopsy. Of the 7776 individuals undergoing medical checkups, 142 (1.8%) were positive for HCV antibody. The positive rate of proteinuria was significantly higher (P<0.030) in individuals with HCV antibody (2.1%) than in those without the antibody (0.6%). Abnormal levels of serum creatinine (5.8 vs. 0%, P=0.025) and complications of cryoglobulinemia (45 vs. 5%, P<0.001) were significantly more common in the 86 patients with chronic hepatitis C (5.8%) than in the 91 patients with other liver diseases. All patients with abnormal levels of serum creatinine had concomitant cryoglobulinemia. Of the nine patients with histologically proven HCV-associated glomerulopathy, four had cryoglobulinemia (all were type II). Elevations of serum creatinine level (4/4 vs. 0/5, P=0.048) and a glomerular legion of membranoproliferative glomerulonephritis (3/4 vs. 0/5, P=0.048), a severe type of glomerulonephritis, were more common in the four patients with cryoglobulinemia than in the remaining five patients. In conclusion, HCV infection was found to be significantly associated with glomerulopathy. In addition, the presence of cryoglobulinemia, which usually accompanies membranoproliferative glomerulonephritis, was found to be an indicator of renal insufficiency in patients with HCV-associated glomerulopathy.
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Gopalani A, Ahuja TS. Prevalence of glomerulopathies in autopsies of patients infected with the hepatitis C virus. Am J Med Sci 2001 Aug;322(2):57-60 Department of Medicine, University of Texas Medical Branch, Galveston, USA. BACKGROUND: Several reports have shown hepatitis C virus (HCV) infection to be associated with various extrahepatic manifestations, including certain forms of glomerulopathy. The most frequently reported glomerulonephritis in patients infected with HCV is either membranoproliferative glomerulonephritis (MPGN) or cryoglobulinemic glomerulonephritis, and HCV has been directly implicated in their pathogenesis. Other investigators have reported a higher prevalence of HCV infection in patients with membranous glomerulonephritis, IgA nephropathy, and focal segmental glomerulosclerosis (FSGS). However, the prevalence of these glomerulopathies in patients infected with HCV is unknown. METHODS: We conducted a 5-year retrospective review to determine prevalence of glomerulopathies in autopsies of patients infected with HCV. The renal histology on the autopsy reports was carefully reviewed for appropriate diagnosis of glomerulonephritis. RESULTS: Of the 114 autopsies of patients infected with HCV during this period, the majority had been incarcerated and had state-mandated autopsies. The mean age of the patients was 46.8 +/- 10 years (+/- SD; range, 19-87). Of the 114 patients, 46 were white, 37 were African American, and 31 were Hispanic. The glomerulopathies seen were 3 MPGN, 2 membranous, 3 HIV-associated nephropathy, 1 idiopathic FSGS, 1 minimal change glomerulonephritis, and 3 diabetic nephropathy. CONCLUSION: We conclude that although HCV is reported to be associated with membranoproliferative and membranous glomerulonephritis, their prevalence in these patients is not common. |
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Inoue K, Kami-ie J, Ohtake S, Wakui S, Machida S, Shirota K. Atypical membranoproliferative glomerulonephritis in a cat. Vet Pathol 2001 Jul;38(4):468-70 Research Institute of Biosciences, Azabu University, Sagamihara, Kanagawa, Japan. Membranoproliferative glomerulonephritis was observed in a 2-year-old male Japanese domestic cat with clinical renal failure. In the glomeruli, moderate mesangial hypercellularity with an increased mesangial matrix and thickening of the capillary walls were prominent. In addition, frequent duplication of the capillary walls, splitting, and spike formation were observed in the glomerular basement membrane. Granular cat IgG and complement component deposition were detected globally along the glomerular capillary walls and in the mesangium. Transmission electron microscopy revealed dense deposits in the subendothelial and subepithelial regions and the mesangium. Mesangial interposition was also observed. These glomerular lesions are also found in humans with membranoproliferative glomerulonephritis type III, which has not been reported in animals.
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Salazar-Exaire D, Rodriguez A, Galindo-Rujana ME, Briones JC, Arenas-Osuna J, Rocha LM, Paniagua R. Membranoproliferative glomerulonephritis associated with a mixed-cell germinal ovary tumor. Am J Nephrol 2001 Jan-Feb;21(1):51-4 Departmento de Nefrologia, Hospital de Especialidades, Centro Medico La Raza, IMSS, Mexico D.F., Mexico. jdsexair@servidor.unam.mx We describe a patient with membranoproliferative glomerulopathy associated with a mixed-cell germinal ovary tumor (embryonal and dysgerminoma components). Advanced renal failure ensued without remission of nephrotic syndrome after surgery. Five other cases of ovary tumor associated with glomerulopathy and reported in the literature are reviewed. The association between membranoproliferative glomerulonephritis and mixed-cell germinal ovary tumor has not been previously reported.
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Hill GS, Delahousse M, Nochy D, Remy P, Mignon F, Mery JP, Bariety J. Predictive power of the second renal biopsy in lupus nephritis: significance of macrophages. Kidney Int 2001 Jan;59(1):304-16 Hopitaux Broussais, St. Louis, Henri Mondor, and Bichat, Paris, France. BACKGROUND: A new Biopsy Index containing the Glomerular Activity (GAI), Tubulointerstitial Activity (TIAI), Chronic Lesion (CLI), and Immunofluorescence (IFI) indices was developed, showing better correlations with clinical and outcome parameters than the National Institutes of Health Activity and Chronicity Indices (AI and CI) in lupus nephritis. This report examines the ability of these indices and individual morphologic variables to predict doubling of serum creatinine (SCr; CRX2). METHODS: Renal biopsies from 71 patients with lupus nephritis with an initial biopsy (Bx1) and systematic control biopsy (Bx2) after six months of therapy were studied. Kaplan-Meier survival curves were developed for each index and morphologic variable at each biopsy. A subset of 30 biopsies was stained with the macrophage marker PGM1. RESULTS: At Bx1, only the TIAI and the quantity of C3 and vascular staining on IF were predictive of CRX2. At Bx2, particularly predictive of CRX2 were the GAI, IFI, Biopsy Index, and BxInfl, a composite variable comprised of all of the inflammatory variables. Among individual variables, glomerular and tubular macrophages correlated the best with clinical and outcome parameters. Crescents and karyorrhexis/fibrinoid necrosis also correlated with outcome. Neither the NIH CI or our CLI, nor the TIAI correlated with outcome. In 30 biopsies stained with PGM1, PGM1+ cells correlated well with glomerular and tubular macrophages identified on routine stains and showed even better correlations with SCr, proteinuria, and progression to renal insufficiency than the latter. A diffuse membranoproliferative (MPGN) pattern was seen in seven patients at Bx1. In four of the seven patients, MPGN disappeared with therapy, and all finished with normal renal function. However, among the three patients in whom MPGN persisted and eight patients in whom MPGN, focal or diffuse, appeared under therapy, six reached end-stage renal disease, and a seventh died with marked renal insufficiency. CONCLUSIONS: The biopsy index and its components correlate modestly with CRX2 at Bx1, but strongly at Bx2, particularly IFI, BxInfl, and glomerular and tubular macrophages. Stains for macrophage markers form a valuable adjunct in interpretation of renal biopsies in systemic lupus erythematosus (SLE). MPGN features do not have an ominous significance at Bx1, but their persistence or appearance under therapy are associated with poor outcome. |
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Author: Nakopoulou L. Title/Abstract: Membranoproliferative glomerulonephritis. Volume: 16 First Page: 71-74. From: Jan 2000 In Journals: Nephrol. Dial. Transplant. |
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