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Danilewicz M, Wagrowska-Danilewicz M: Lupus and nonlupus membranous glomerulopathy. Quantitative comparison of the subepithelial deposits and glomerular basement membrane including clinicomorphologic correlations. Gen Diagn Pathol 1997 Jun;142(5-6):305-10 . Department of Pathology (Morphometry Division), Medical Academy of Lodz, Poland. hobo@psk2.am.lodz.pl  We examined quantitatively 11 renal biopsy specimens from patients with class Va WHO lupus membranous glomerulopathy (LMGN) and 16 from patients with primary (nonlupus) membranous glomerulopathy (NLMGN) for whom both light and electron microscopy as well as immunofluorescence microscopy and full clinical data were available and compared these specimens with six cases of normal controls. In LMGN, subepithelial deposits resembled those seen in stage III of membranous glomerulopathy (MGN) according to the scheme proposed by Churg's group, i.e., for the present study only advanced cases of NLMGN (stage III according to this scheme) were selected. The electron micrographs were scanned in Primax flatbed A4 scanner and morphometric investigations were then performed by means of a computer image analysis system to compare glomerular basement membrane (GBM) thickness and the electron-microscopic density of the deposits in LMGN and NLMGN as well as to study whether these parameters could correlate with the clinical data. The study revealed that in LMGN the GBM thickness and the electron-microscopic density of the deposits were significantly increased in comparison with NLMGN. It should also be noted that both in LMGN and NLMGN groups the degree of proteinuria was closely correlated with the density of the deposits, but not with the GBM thickness. Moreover, no correlations were found between serum creatinine and the GBM thickness as well as between serum creatinine and the density of the deposits in these groups. In conclusion, the present data confirm that in LMGN and NLMGN proteinuria mainly depends on density of the subepithelial deposits. Furthermore, in cases with especially high density of these deposits systemic lupus erythematosus (SLE) should be taken into consideration, even if this etiology was not clinically suggested at the time of biopsy.
Reichert LJ, Koene RA, Wetzels JF: Prognostic factors in idiopathic membranous nephropathy. Am J Kidney Dis 1998 Jan;31(1):1-11. Department of Medicine, University Hospital Nijmegen, The Netherlands.  Membranous nephropathy is the most frequent cause of glomerulonephritis in adults with nephrotic syndrome. Approximately one quarter of the patients develop end-stage renal disease. Another quarter enters complete remission during follow-up. Treating all patients with membranous nephropathy with immunosuppressive drugs would unnecessarily expose at least one quarter of the patients to these toxic drugs. Identifying patients at highest risk would allow tailor-made treatment. Many risk factors have been found, such as male sex, HLA type DR3+/B8+, white race, advanced age, and tubulointerstitial changes or focal sclerosis found with renal biopsy. In addition, nephrotic syndrome, elevation of immunoglobulin G excretion or beta2-microglobulin excretion, low serum albumin, high serum cholesterol, an elevation of urinary excretion of complement activation products, impaired renal function at diagnosis, and, finally, hypertension are associated with a higher risk of renal function deterioration during follow-up. We have critically reviewed the literature and summarized the clinical significance of the above-mentioned risk factors in predicting subsequent renal function deterioration in patients with membranous nephropathy.
Yamamoto S, Inaba S, Yoshida R, Takahashi T, Ishihara S, Sakai Y, Arai M, Kurose K, Matsukura H, Miyawaki T : Clinicopathological characteristics of the focal and segmental form of idiopathic membranous nephropathy: comparison with the typical form of this disease. Acta Paediatr Jpn 1997 Jun;39(3):349-53. Department of Pediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Japan. Although idiopathic membranous nephropathy (IMN) is thought to represent a diffuse glomerulopathy, it was found that three of 31 children histologically diagnosed as IMN showed focal and segmental deposition of immunoglobulin G (IgG) and C3 on the glomerular capillary walls. The present study attempted to comparatively investigate clinical and pathological features of the diffuse group and the focal segmental group in 31 IMN children. Immunofluorescence study revealed that 28 of 31 IMN exhibited diffuse granular deposition of IgG along glomerular capillary walls. In contrast, focal and segmental deposition of IgG and C3 was noted in three children with IMN. In addition, focal and segmental electron-dense deposits were identified in these cases. In two children of the focal segmental group, immunofluorescent patterns of IgG deposition were unchanged even at the second biopsy. The focal segmental form of IMN tended to occur in younger children than diffuse IMN. However, other clinical parameters such as the range of proteinuria, hematuria, serum albumin and prognosis did not show any significant differences between both groups. Electrophoretic profiles of urinary proteins on sodium dodecylsulfate-polyacrylamide gel electrophoresis were not different between both groups. It is proposed that the focal segmental form of IMN may have a distinctive glomerulopathy from the typical form of IMN.
Roberts IS, Burrows C, Shanks JH, Venning M, McWilliam LJ :Interstitial myofibroblasts: predictors of progression in membranous nephropathy. J Clin Pathol 1997 Feb;50(2):123-7. Department of Pathological Sciences, University of Manchester, USA. AIMS: To determine the role of interstitial myofibroblasts in the progression of membranous nephropathy; and to assess the predictive value of quantifying myofibroblasts in determining long term renal outcome. METHODS: All cases of membranous nephropathy, diagnosed by renal biopsy at University Hospital of South Manchester between 1984 and 1987, were studied retrospectively. The biopsy specimens (n = 26) were reviewed and analysed morphometrically to measure interstitial volume as a proportion of the total volume of renal cortex, and numbers of interstitial myofibroblasts (cells positive for alpha-smooth muscle actin within the interstitium). Clinical data, with a follow up of seven to eight years, was available for 24 patients, and renal outcome was correlated with pathological changes in the initial diagnostic biopsy specimen. RESULTS: The number of myofibroblasts and interstitial volume were inversely correlated with creatinine clearance at the initial biopsy, and at the end of follow up. Percentage sclerosed glomeruli or stage of glomerular disease, assessed by electron microscopy, did not correlate with renal function at initial biopsy or during follow up. The number of myofibroblasts, but not interstitial volume, correlated with severity of proteinuria at initial biopsy. Of 15 biopsy specimens showing no or mild interstitial fibrosis, four showed a notable increase in the number of interstitial myofibroblasts. All of these patients developed chronic renal failure, compared with three of 11 patients whose specimens showed no or a mild increase in myofibroblast numbers. CONCLUSIONS: Interstitial myofibroblasts play a role in the development of interstitial fibrosis and progressive renal failure in membranous nephropathy. Increased numbers of myofibroblasts in biopsy specimens showing only mild fibrosis may predict subsequent chronic renal failure.
Nishi S, Ueno M, Shimada H, Karasawa R, Nakamaru T, Miyakawa Y, Arakawa M : Prognosis of Japanese membranous nephropathy patients with nephrotic syndrome. Kidney Int Suppl 1997 Dec;63:S177-8. Department of Medicine (II), Niigata University School of Medicine, Japan. We retrospectively investigated the prognosis and efficacy of various treatments in 58 Japanese patients with primary membranous nephropathy (MN). Patients were treated with prednisolone (PSL) + immunosuppressive (IS) agents (N = 22). PSL alone (N = 23), IS agents alone (N = 5) and aspirin or dipyridamole (N = 8). Overall, 25 patients (43.1%) achieved complete remission (CR), 11 (18.9%) achieved partial remission (PR) and 22 (37.9%) were non-responders (NR). The 10-year survival rate was 90% and the 10-year CR rate was 61.8% as determined by Kaplan-Meier analysis. There was no significant difference in the CR among treatment groups. Of the 22 patients in the PSL + IS group, 3 progressed to end-stage renal disease and 2, who were more than 65 years old, died of pneumonia. The clinical and histological data at renal biopsy did not significantly differ among the treatment groups. In conclusion, the overall prognosis of MN was excellent. Treatment with PSL and/or IS agents did not appear to be superior to treatment with aspirin or dipyridamole.
Marx BE, Marx M: Prognosis of idiopathic membranous nephropathy: a methodologic meta-analysis. Kidney Int 1997 Mar;51(3):873-9. Medizinische Klinik IV mit Poliklinik, Universitat Erlangen-Nurnberg, Germany. Results in studies on prognosis and treatment of membranous nephropathy are conflicting. The aim of this investigation was to analyze the methodology of the existing research and to identify sources of these conflicting results. Studies published on prognosis of membranous nephropathy from 1970 to 1995 were identified using a Medline database literature search. The criteria for inclusion in the methodologic analysis were: (1) original article; (2) cohort study or clinical trial with > or = 50 adults; (3) zero time near the diagnostic renal biopsy; and (4) follow-up > or = six months. Ten well-accepted methodologic standards for prognostic research were applied to each study and the compliance was evaluated. Among the 26 studies that met the inclusion criteria, the median number of standards fulfilled was 4 and the highest was 7. The proportion of studies adhering to the individual standards was: (1) adequate diagnostic criteria, 35%; (2) definite end point, 46%; (3) adequate analysis of a surrogate end point, 52%; (4) analysis of baseline severity, 0%; (5) indication of baseline frequency for candidate predictors, 35%; (6) reproducible classification of predictors, 85%; (7) multivariable analysis, 50%; (8) identification of the variables' importance in multivariable analysis, 38%; (9) evaluation of the effect of treatment on predictors, 19%; and (10) adequate analysis of censored patients, 58%. We conclude that basic methodologic principles have frequently been disregarded. The consideration of these standards in future research can improve the interpretability and applicability of results and help reconcile conflict when results are compared among different studies.
Reichert LJ, Koene RA, Wetzels JF: Urinary IgG excretion as a prognostic factor in idiopathic membranous nephropathy. Clin Nephrol 1997 Aug;48(2):79-84. Department of Medicine, University Hospital Nijmegen, The Netherlands. In membranous nephropathy it would be of great value to be able to identify in an early phase patients at highest risk for disease progression, since potentially toxic treatment could then be restricted to these patients only. We measured renal hemodynamics, serum proteins and urinary protein excretion in 22 patients with membranous nephropathy, nephrotic syndrome and normal renal function (endogenous creatinine clearance > 85 ml/min). These patients were followed for a mean of 56 months. Renal function deteriorated in nine patients. When using univariate analysis, deterioration of renal) function appeared to be associated with a low serum albumin and transferrin, high urinary transferrin, beta-microglobulin, and IgG excretion, but not with renal hemodynamics. A step-up procedure, used for selecting variables associated with survival, showed that IgG excretion was independently associated with renal function deterioration. In patients with membranous nephropathy and normal renal function, the urinary excretion rate of IgG predicts future renal function outcome.