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Elahi T, Ahmed S, Mubarak M. Short-term renal and patient outcomes of primary immunoglobulin-associated mesangiocapillary glomerulonephritis: Insights from a developing country. World J Nephrol 2024; 13:98969. [PMID: 39723356 PMCID: PMC11572649 DOI: 10.5527/wjn.v13.i4.98969] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 09/09/2024] [Accepted: 09/19/2024] [Indexed: 11/07/2024] Open
Abstract
BACKGROUND Primary immunoglobulin (Ig)-associated mesangiocapillary glomerulonephritis (Ig-MCGN) is an immune complex glomerulonephritis of unknown etiology. It is a common cause of chronic kidney disease in developing countries. There is limited data available on renal and patient outcomes of this disease from developing countries. AIM To determine the short-term renal and patient outcomes of adults with a tissue-confirmed diagnosis of primary Ig-MCGN at a single center in Pakistan. METHODS A retrospective cohort study of adult patients was conducted on biopsy-proven Ig-MCGN cases diagnosed between 1998 and 2019 at the Sindh Institute of Urology and Transplantation, Karachi, Pakistan. Secondary causes were excluded. The primary endpoint was renal survival without end-stage kidney disease (ESKD) or mortality. The secondary endpoint was the rate of remission during the 2-year follow-up period. Survival curves were made with the use of Kaplan-Meier estimates. RESULTS A total of 163 patients were included in the study and their mean follow-up duration was 29.45 months ± 21.28 months. Among baseline characteristics, young age, lower estimated glomerular filtration rate, requirement of kidney replacement therapy, presence of crescents, and severity of interstitial fibrosis and tubular atrophy were found to have a significant association with renal outcomes. The renal outcomes were negatively correlated with the presence of hypertension, level of complements, and degree of proteinuria. In all, 63 (37.4%) patients were treated with steroids and 21 (13%) received combination therapy (cyclophosphamide with steroids). At 2 years, 124 (76.07%) patients were in complete remission or partial remission [56 (34.3%) and 68 (41.71%), respectively], while 32 (19.63%) patients progressed to ESKD and 7 (4.29%) patients died. CONCLUSION The outcomes of primary Ig-MCGN are guarded in Pakistan and require further prospective studies to improve our understanding of this relatively common disease so that more personalized treatment approaches can be developed.
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Affiliation(s)
- Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
| | - Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
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Elahi T, Ahmed S, Ahmed E, Mubarak M. Clinicopathological characteristics and outcomes of adult patients with idiopathic membranoproliferative glomerulonephritis according to an immunofluorescence-based classification. J Nephrol 2024; 37:2255-2265. [PMID: 39400860 DOI: 10.1007/s40620-024-02083-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2024] [Accepted: 08/16/2024] [Indexed: 10/15/2024]
Abstract
BACKGROUND The classification of membranoproliferative glomerulonephritis (MPGN) into immune complex-mediated MPGN and complement-mediated MPGN on immunofluorescence has provided insights into two distinct disease processes. There are limited data available on renal outcomes of MPGN from developing countries. METHODS A retrospective analysis was conducted on biopsy-proven MPGN cases diagnosed between 1998 and 2018 at the Sindh Institute of Urology and Transplantation (SIUT). Secondary causes were excluded. Patients were reclassified as immune complex-mediated-MPGN and complement-mediated-MPGN based on immunofluorescence results. The clinicopathological findings and outcomes of the two groups were compared. RESULTS In total, 213 patients with idiopathic MPGN were identified. Among these, 163 (76.5%) were reclassified as immune complex-mediated-MPGN and 50 (23.4%) as complement-mediated-MPGN. No significant differences were found between the two groups regarding age, gender, clinical characteristics, biopsy indications, biopsy findings, and renal function at presentation. Overall, 63 subjects (38.7%) with immune complex-mediated-MPGN and 27 (54%) with complement-mediated-MPGN received immunosuppressive agents (p = 0.08). Complete and partial remission rates were higher in immune complex-mediated-MPGN than in complement-mediated-MPGN (76% vs 58%, p < 0.05). At two years, median estimated glomerualr filtration rate (eGFR) tended to be higher in patients with immune complex-mediated-MPGN 91.2 (45.4-113.7) vs 83.45(34.6-102.50) ml/min/1.73 m2, p = 0.22) with significantly better renal survival (76% vs 58%, p = 0.03). Comparatively, more patients progressed to end-stage kidney disease (ESKD) in the complement-mediated-MPGN group (32% vs 19.6%, p = 0.06), with increased overall mortality (5 (10%) vs 7 (4.3%), p = 0.12). CONCLUSION The clinicopathological features at presentation of complement-mediated-MPGN are similar to those of immune complex-mediated-MPGN. However, it is less frequent and overall prognosis is less favorable.
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Affiliation(s)
- Tabassum Elahi
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan.
| | - Saima Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan
| | - Ejaz Ahmed
- Department of Nephrology, Sindh Institute of Urology and Transplantation, Chand Bibi Road Near Civil Hospital Karachi, Karachi, 74200, Pakistan
| | - Muhammed Mubarak
- Department of Histopathology, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
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Therapy and outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis. Pediatr Nephrol 2021; 36:591-600. [PMID: 32886193 DOI: 10.1007/s00467-020-04736-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 07/13/2020] [Accepted: 07/31/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Data on therapy and outcome of dense deposit disease (DDD), C3 glomerulonephritis (C3GN), and immune-complex MPGN (IC-MPGN) in children are limited. METHODS In this retrospective single-center study from 2007 to 2019, kidney biopsies were reviewed to include patients aged <18-years with C3 glomerulopathy and IC-MPGN. Initial immunosuppression comprised prednisolone, mycophenolate mofetil (n = 51), tacrolimus (n = 11), and/or IV cyclophosphamide (n = 20). Clinicopathological features, response to therapy, and adverse outcome (eGFRcr < 15 mL/min/1.73 m2 or death) were evaluated. RESULTS A total of 92 patients were classified as DDD (n = 48, 52.2%), C3GN (n = 26, 28.3%), and IC-MPGN (n = 18, 19.6%) by immunohistochemistry and electron microscopy; 8 patients with DDD were misclassified as IC-MPGN on immunofluorescence. At last follow-up (median 4.3 years), complete or partial remission occurred in 28.5, 36.1, and 16.7% patients with DDD, C3GN, and IC-MPGN, respectively. Serum albumin at onset < 2.5 g/dL (HR = 0.29, P = 0.005) and persistently low serum C3 (HR = 0.34, P = 0.02) were associated with lack of remission. The 5-year kidney survival was 62.6, 85.5, and 88.5% in patients with DDD, C3GN, and IC-MPGN, respectively (log-rank, P = 0.006). Presentation as rapidly progressive GN (HR = 11.2, P < 0.001), age > 10 years at onset (HR = 4.0, P = 0.004), and DDD (HR = 4.2, P = 0.02) were independently associated with adverse outcome; achieving remission was protective (HR = 0.04; P < 0.001). CONCLUSION Outcome in patients with C3 glomerulopathy and IC-MPGN was unsatisfactory, and only a small proportion of patients achieved complete or partial remission. Patients with DDD were more likely to present with rapidly progressive GN and were at higher risk of adverse outcomes, including kidney failure.
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Corvillo F, Okrój M, Nozal P, Melgosa M, Sánchez-Corral P, López-Trascasa M. Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations. Front Immunol 2019; 10:886. [PMID: 31068950 PMCID: PMC6491685 DOI: 10.3389/fimmu.2019.00886] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2018] [Accepted: 04/05/2019] [Indexed: 12/18/2022] Open
Abstract
Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephritic factor has been characterized by the ability to stabilize C5 convertase of the alternative pathway (C5NeF). In addition, there are autoantibodies against assembled C3/C5 convertase of the classical and lectin pathways (C4NeF). These autoantibodies have been mainly associated with kidney diseases, like C3 glomerulopathy and immune complex-associated-membranoproliferative glomerulonephritis. Other clinical situations where these autoantibodies have been observed include infections and autoimmune disorders such as systemic lupus erythematosus and acquired partial lipodystrophy. C3 hypocomplementemia is a common finding in all patients with nephritic factors. The methods to measure nephritic factors are not standardized, technically complex, and lack of an appropriate quality control. This review will be focused in the description of the mechanism of action of the three known nephritic factors (C3NeF, C4NeF, and C5NeF), and their association with human diseases. Moreover, we present an overview regarding the diagnostic tools for its detection, and the main therapeutic approach for the patients with nephritic factors.
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Affiliation(s)
- Fernando Corvillo
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER U754), Madrid, Spain
| | - Marcin Okrój
- Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdansk and Medical University of Gdansk, Gdansk, Poland
| | - Pilar Nozal
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER U754), Madrid, Spain.,Immunology Unit, La Paz University Hospital, Madrid, Spain
| | - Marta Melgosa
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Pediatric Nephrology Unit, La Paz University Hospital, Madrid, Spain
| | - Pilar Sánchez-Corral
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Center for Biomedical Network Research on Rare Diseases (CIBERER U754), Madrid, Spain
| | - Margarita López-Trascasa
- Complement Research Group, Hospital La Paz Institute for Health Research (IdiPAZ), La Paz University Hospital, Madrid, Spain.,Departamento de Medicina, Universidad Autónoma de Madrid, Madrid, Spain
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Characteristics of membranoproliferative glomerulonephritis based on a new classification at a single center. Clin Exp Nephrol 2019; 23:852-858. [PMID: 30854618 DOI: 10.1007/s10157-019-01716-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 02/13/2019] [Indexed: 01/30/2023]
Abstract
BACKGROUND Recently, a new classification has been established for membranoproliferative glomerulonephritis (MPGN). However, the effect of the new classification on MPGN treatment is not fully understood. METHODS We conducted a retrospective study of 87 patients with biopsies diagnosed as MPGN. We reclassified 87 MPGN patients diagnosed between 1977 and 2014 at our hospital, according to the new classification, and analyzed both primary immune complex (IC)- and Alternative pathway (AP)-mediated MPGN [corrected] in terms of clinicopathological features, treatment, and renal prognosis. RESULTS Proteinuria was abundant in the IC-mediated MPGN group (p = 0.0063), and the serum albumin level was significantly lower in the IC-mediated MPGN group (p = 0.0186). The serum C3 value was significantly lower in the CP-mediated MPGN group (p = 0.0317). Serum CH50 values were also lower in the CP-mediated MPGN group (p = 0.0404). However, glomerular deposition of C3 showed no significant differences in immunofluorescence findings. The 148.6-month renal survival rate was similar in both groups (p = 0.445). CONCLUSION These results suggested no significant differences in complement activation of the solid phase in local glomeruli and therefore equivalent in renal prognosis [corrected].
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Wong EKS, Kavanagh D. Diseases of complement dysregulation-an overview. Semin Immunopathol 2018; 40:49-64. [PMID: 29327071 PMCID: PMC5794843 DOI: 10.1007/s00281-017-0663-8] [Citation(s) in RCA: 76] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Accepted: 11/01/2017] [Indexed: 02/07/2023]
Abstract
Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of complement dysregulation. Although complement overactivation is common to all, cell surface alternative pathway dysregulation (aHUS), fluid phase alternative pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates resulting in the very different phenotypes seen in these diseases. The mechanism underlying the dysregulation also varies with predominant acquired autoimmune (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS) predisposing to disease. Eculizumab has revolutionized the treatment of PNH and aHUS although has been less successful in C3G. With the next generation of complement therapeutic in late stage development, these archetypal complement diseases will provide the initial targets.
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Affiliation(s)
- Edwin K S Wong
- The National Renal Complement Therapeutics Centre, aHUS Service, Building 26, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK.,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - David Kavanagh
- The National Renal Complement Therapeutics Centre, aHUS Service, Building 26, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne, NE1 4LP, UK. .,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.
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Rituximab for Treatment of Membranoproliferative Glomerulonephritis and C3 Glomerulopathies. BIOMED RESEARCH INTERNATIONAL 2017; 2017:2180508. [PMID: 28573137 PMCID: PMC5440792 DOI: 10.1155/2017/2180508] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/03/2017] [Accepted: 04/20/2017] [Indexed: 01/18/2023]
Abstract
Membranoproliferative glomerulonephritis (MPGN) is a histological pattern of injury resulting from predominantly subendothelial and mesangial deposition of immunoglobulins or complement factors with subsequent inflammation and proliferation particularly of the glomerular basement membrane. Recent classification of MPGN is based on pathogenesis dividing MPGN into immunoglobulin-associated MPGN and complement-mediated C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Current guidelines suggest treatment with steroids, cytotoxic agents with or without plasmapheresis only for subjects with progressive disease, that is, nephrotic range proteinuria and decline of renal function. Rituximab, a chimeric B-cell depleting anti-CD20 antibody, has emerged in the last decade as a treatment option for patients with primary glomerular diseases such as minimal change disease, focal-segmental glomerulosclerosis, or idiopathic membranous nephropathy. However, data on the use of rituximab in MPGN, C3GN, and DDD are limited to case reports and retrospective case series. Patients with immunoglobulin-associated and idiopathic MPGN who were treated with rituximab showed partial and complete responses in the majorities of cases. However, rituximab was not effective in few cases of C3GN and DDD. Despite promising results in immunoglobulin-associated and idiopathic MPGN, current evidence on this treatment remains weak, and controlled and prospective data are urgently needed.
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Lionaki S, Gakiopoulou H, Boletis JN. Understanding the complement-mediated glomerular diseases: focus on membranoproliferative glomerulonephritis and C3 glomerulopathies. APMIS 2016; 124:725-35. [PMID: 27356907 DOI: 10.1111/apm.12566] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Accepted: 05/13/2016] [Indexed: 01/16/2023]
Abstract
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.
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Affiliation(s)
- Sophia Lionaki
- Nephrology Department, Laiko Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Hara Gakiopoulou
- Department of Pathology, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - John N Boletis
- Nephrology Department, Laiko Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece
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Strati P, Nasr SH, Leung N, Hanson CA, Chaffee KG, Schwager SM, Achenbach SJ, Call TG, Parikh SA, Ding W, Kay NE, Shanafelt TD. Renal complications in chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis: the Mayo Clinic experience. Haematologica 2015; 100:1180-8. [PMID: 26088927 DOI: 10.3324/haematol.2015.128793] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2015] [Accepted: 06/10/2015] [Indexed: 11/09/2022] Open
Abstract
While the renal complications of plasma cell dyscrasia have been well-described, most information in patients with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis is derived from case reports. This is a retrospective analysis of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who underwent kidney biopsy for renal insufficiency and/or nephrotic syndrome. Between January 1995 and June 2014, 49 of 4,024 (1.2%) patients with chronic lymphocytic leukemia (n=44) or monoclonal B-cell lymphocytosis (n=5) had a renal biopsy: 34 (69%) for renal insufficiency and 15 (31%) for nephrotic syndrome. The most common findings on biopsy were: membranoproliferative glomerulonephritis (n=10, 20%), chronic lymphocytic leukemia interstitial infiltration as primary etiology (n=6, 12%), thrombotic microangiopathy (n=6, 12%), and minimal change disease (n=5, 10%). All five membranoproliferative glomerulonephritis patients treated with rituximab, cyclophosphamide and prednisone-based regimens had recovery of renal function compared to 0/3 patients treated with rituximab with or without steroids. Chronic lymphocytic leukemia infiltration as the primary cause of renal abnormalities was typically observed in relapsed/refractory patients (4/6). Thrombotic microangiopathy primarily occurred as a treatment-related toxicity of pentostatin (4/6 cases), and resolved with drug discontinuation. All cases of minimal change disease resolved with immunosuppressive agents only. Renal biopsy plays an important role in the management of patients with chronic lymphocytic leukemia or monoclonal B-cell lymphocytosis who develop renal failure and/or nephrotic syndrome.
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Affiliation(s)
- Paolo Strati
- Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Samih H Nasr
- Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Nelson Leung
- Mayo Clinic College of Medicine, Rochester, MN, USA
| | | | | | | | | | | | | | - Wei Ding
- Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Neil E Kay
- Mayo Clinic College of Medicine, Rochester, MN, USA
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Abstract
Membranoproliferative GN represents a pattern of injury seen on light microscopy. Historically, findings on electron microscopy have been used to further subclassify this pathologic entity. Recent advances in understanding of the underlying pathobiology have led to a proposed classification scheme based on immunofluorescence findings. Dysregulation of the complement system has been shown to be a major risk factor for the development of a membranoproliferative GN pattern of injury on kidney biopsy. Evaluation and treatment of this complex disorder rest on defining the underlying mechanisms.
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Affiliation(s)
- Naveed Masani
- Division of Nephrology, Winthrop University Hospital, Mineola, New York, †Division of Kidney Diseases and Hypertension, Hofstra North Shore-Long Island Jewish School of Medicine, Great Neck, New York
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C3 nephritic factor associated with C3 glomerulopathy in children. Pediatr Nephrol 2014; 29:85-94. [PMID: 24068526 DOI: 10.1007/s00467-013-2605-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 07/23/2013] [Accepted: 07/25/2013] [Indexed: 01/26/2023]
Abstract
BACKGROUND C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF. METHODS We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes. RESULTS Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases. CONCLUSIONS C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.
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Pirisi M, Faedda R, Satta A, Bartoli E. Immunosuppressive treatment for idiopathic nephrotic syndrome with corticosteroids and cyclophosphamide: factors associated with a favourable outcome. Clin Drug Investig 2013; 16:211-8. [PMID: 18370542 DOI: 10.2165/00044011-199816030-00005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
OBJECTIVE We report the results of a combined immunosuppressive schedule for the treatment of patients with idiopathic nephrotic syndrome, in which prednisone and cyclophosphamide were given in four phases: induction, maintenance, tapering and discontinuation. PATIENTS AND OUTCOME MEASURES Sixty-seven patients with nephrotic syndrome, followed for an average of 7.1 +/- 4.5 years, were studied. Treatment outcomes were remission, progression, end-stage renal disease and death. RESULTS At the end of the follow-up, 72% of patients maintained a complete remission. Stepwise logistic regression showed that the cumulative dose of cyclophosphamide was the only independent predictor of a favourable outcome, being associated both with complete remission of the nephrotic syndrome and with lack of progression to chronic renal failure. CONCLUSION We suggest that the combination treatment may be indicated in all histological subgroups of nephrotic syndrome, provided that prednisone is given at high doses on alternate days, cyclophosphamide is given for 6 months, and relapses are treated with the same schedule. The adverse effects of treatment, however, require the adoption of a programme to prevent bone loss, infertility, bladder cancer and infections.
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Affiliation(s)
- M Pirisi
- Cattedra di Medicina Interna, DPMSC, Università degli Studi, Udine, Italy
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Positive C1q staining associated with poor renal outcome in membranoproliferative glomerulonephritis. Clin Exp Nephrol 2012; 17:92-8. [PMID: 22821391 DOI: 10.1007/s10157-012-0667-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2012] [Accepted: 06/27/2012] [Indexed: 10/28/2022]
Abstract
BACKGROUND Pathogenesis and clinical prognosis of membranoproliferative glomerulonephritis (MPGN) has not yet been established. METHODS We conducted a retrospective study of 41 patients with MPGN (type I and III) and examined the renal survival. In addition, factors contributing to survival time were analyzed. RESULTS Fourteen patients (34 %) were classified into the renal death group. Patients with nephrotic syndrome and positive C1q staining of glomerular deposits showed a particularly poor prognosis. Significantly higher frequency of nephrotic syndrome and higher urinary protein excretion were observed in the renal death group (p = 0.0002, p = 0.0002) than in the renal survival group. The intensity of C1q staining was positively correlated with the severity of the proteinuria (p = 0.004). Factors that influenced the survival time were positive C1q staining of glomerular deposits (p = 0.003), presence of nephrotic syndrome (p = 0.004), serum albumin (p = 0.02), and proteinuria (p = 0.04). CONCLUSIONS C1q staining in glomerular deposits and nephrotic syndrome were important factors influencing the prognosis and outcome in MPGN patients. C1q deposition may play a key role in the pathogenesis of MPGN, as evidenced by numerous observations, such as induction of proteinuria.
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Affiliation(s)
- Sanjeev Sethi
- Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st St. SW, Rochester, MN 55905, USA.
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Alchi B, Jayne D. Membranoproliferative glomerulonephritis. Pediatr Nephrol 2010; 25:1409-18. [PMID: 19908070 PMCID: PMC2887509 DOI: 10.1007/s00467-009-1322-7] [Citation(s) in RCA: 95] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Revised: 08/21/2009] [Accepted: 08/27/2009] [Indexed: 01/31/2023]
Abstract
Membranoproliferative glomerulonephritis is an uncommon kidney disorder characterized by mesangial cell proliferation and structural changes in glomerular capillary walls. It can be subdivided into idiopathic and secondary forms, which are differentially diagnosed by a review of clinical features, laboratory data, and renal histopathology. Three types-I, II, and III-have been defined by pathologic features. All three types are associated with hypocomplementemia, but they manifest somewhat different mechanisms of complement activation. Type II, also known as "dense deposit disease", is associated with the presence of C3-nephritic factor. Membranoproliferative glomerulonephritis primarily affects children and young adults, with patients presenting with nephrotic or nephritic syndrome or with asymptomatic renal disease. This type of glomerulonephritis often progresses slowly to end-stage renal disease, and it tends to recur after renal transplantation, especially type II. The efficacy of various forms of treatment remains controversial; however, long-term steroid treatment seems to be effective in children with nephrotic-range proteinuria. Improvement in renal outcomes largely relies on the evaluation of more selective agents in carefully controlled studies.
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Affiliation(s)
- Bassam Alchi
- Renal Unit, Addenbrooke’s Hospital, Box 118, Hills road, Cambridge, CB2 0QQ UK
| | - David Jayne
- Renal Unit, Addenbrooke’s Hospital, Box 118, Hills road, Cambridge, CB2 0QQ UK
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Soto K, Wu YL, Ortiz A, Aparício SR, Yu CY. Familial C4B deficiency and immune complex glomerulonephritis. Clin Immunol 2010; 137:166-75. [PMID: 20580617 DOI: 10.1016/j.clim.2010.06.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2010] [Revised: 05/29/2010] [Accepted: 06/02/2010] [Indexed: 11/16/2022]
Abstract
Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits.
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Affiliation(s)
- K Soto
- Department of Nephrology, Hospital Fernando Fonseca, Lisbon, Portugal.
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Arikan H, Koc M, Cakalagaoglu F, Tuglular S, Ozener C, Akoglu E. Histopathological changes and tumour necrosis factor-alpha, transforming growth factor-beta and tenascin expression in patients with primary type I membranoproliferative glomerulonephritis in remission. Nephrology (Carlton) 2009; 14:219-26. [PMID: 19298642 DOI: 10.1111/j.1440-1797.2008.01048.x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
AIM Primary type I membranoproliferative glomerulonephritis (MPGN) is a rare cause of glomerular disease with a high relapse rate and poor prognosis. The aim of this study was: (i) to evaluate the histopathological findings associated with remission; and (ii) to document the possible clinical and histopathological factors predicting relapses. METHODS Eleven type I MPGN patients (five men, six women; mean age, 38.8+/-13.5 years) who were in remission for at least 1 year after the cessation of immunosuppressive drugs were re-biopsied. The intensity of immunostaining for tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, and tenascin was graded from 0 (no staining) to 3+ (maximum staining). RESULTS Mean baseline mesangial cellularity score and tubulointerstitial infiltration score were reduced and mesangial matrix expansion score was increased at protocol re-biopsies compared to baseline. The glomerular and tubulointerstitial staining scores for TGF-beta1 and tenascin were higher than that of baseline. Reduced tubulointerstitial TNF-alpha expression was found in re-biopsy specimens compared to baseline. Patients have been followed for a mean time of 51.5+/-22.2 months after the protocol biopsy. Eight patients had a relapse. Mesangial cellularity score and glomerular tenascin expression at re-biopsy specimens were higher in relapsed patients compared to those without a relapse. CONCLUSION Our study shows that mesangial cellularity and tubulointerstitial cell infiltration are reducing whereas mesangial matrix expansion, glomerular and tubulointerstitial TGF-beta1 and tenascin expression are increasing with remission. The higher mesangial cell proliferation and glomerular tenascin scores in remission are associated with the development of relapse.
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Affiliation(s)
- Hakki Arikan
- Division of Nephrology, Department of Medicine, Marmara Medical School, Istanbul, Turkey.
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Remission of resistant MPGN type I with mycophenolate mofetil and steroids. Pediatr Nephrol 2009; 24:597-600. [PMID: 18972137 DOI: 10.1007/s00467-008-1023-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2008] [Revised: 09/09/2008] [Accepted: 09/11/2008] [Indexed: 10/21/2022]
Abstract
Very few studies have been published on how to treat children with membranoproliferative glomerulonephritis type I (MPGN I), and as yet there is only one report on the use of mycophenolate mofetil (MMF) in children with MPGN I. We report a 12-year-old boy who presented with edema, hypertension, nephrotic range proteinuria, and microscopic hematuria following an upper respiratory tract infection. Laboratory tests revealed a serum creatinine of 90 micromol/l, albumin of 20 g/l, and a C3 of 0.11 g/l (normal range: 0.7-1.4). Renal biopsy showed the presence of MPGN I. Upon failure to induce remission with prednisone, we started the patient on MMF at 500 mg/day (300 mg/m(2)), increasing up to a final dose of 2 g/day (1200 mg/m(2)), with a MMF metabolite mycophenolic acid (MPA) target range of 2-5 mg/l. Prednisone was subsequently reduced to alternate day therapy and gradually weaned to 7.5 mg on alternate days over 9 months. Within 4 months of starting MMF therapy, there was significant improvement in serum creatinine (decrease from 156 to 64 micromol/l), serum albumin (increase from 23 to 40 g/l), and proteinuria (decrease from 13 g/day to 40 mg/day). Twelve months following the introduction of MMF into his therapeutic regimen, he remains in remission with no further relapses. In summary, this case suggests that there may be potential benefit for use of MMF in children with refractory MPGN I, which supports the rationale for prospectively evaluating MMF treatment in a treatment trial of refractory MPGN I.
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Prognostic factors in children with membranoproliferative glomerulonephritis type I. Pediatr Nephrol 2008; 23:929-35. [PMID: 18297315 DOI: 10.1007/s00467-008-0754-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2007] [Revised: 12/09/2007] [Accepted: 12/14/2007] [Indexed: 10/22/2022]
Abstract
The clinical outcome of patients with membranoproliferative glomerulonephritis (MPGN) varies, with some patients progressing to end-stage renal disease. The aim of this retrospective study was to analyze the initial clinical signs and laboratory test results associated with an MPGN prognosis. The study cohort consisted of 47 patients with idiopathic MPGN Type I treated at the National Institute of Pediatrics, Mexico City, between 1971 and 2001. The median follow-up was 3 years. The three different outcomes of interest were death, renal failure, and nephrotic syndrome. The patients' ages ranged between 4 and 16 years. All patients had different degrees of proteinuria, hyperlipidemia, and microscopic/macroscopic hematuria, and 85.1% of them showed hypocomplementemia. Clinical outcomes varied, however, the most common was nephrotic syndrome, either alone or combined with other syndromes, which accounted for 74.5% of all cases. Fifteen patients died. Treatment with methylprednisolone improved the patient's condition, while the use of chloroquine or cyclophosphamide worsened it. Twenty-two patients had some degree of renal failure; glomerular filtration rate (GFR) levels and albumin values were negatively associated to renal failure, while treatment with methylprednisolone decreased the probability of renal failure. Nephrotic syndrome persisted in 18 patients; hemolytic complement and hemoglobin values were negatively associated with nephrotic syndrome, while macroscopic hematuria was positively associated with it. Signs that suggested a poor prognosis during diagnosis were low GFR, low albumin, low hemolytic complement, and macroscopic hematuria. Treatment with methylprednisolone seemed to improve prognosis, however, this needs to be confirmed with randomized studies.
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Yanagihara T, Hayakawa M, Yoshida J, Tsuchiya M, Morita T, Murakami M, Fukunaga Y. Long-term follow-up of diffuse membranoproliferative glomerulonephritis type I. Pediatr Nephrol 2005; 20:585-90. [PMID: 15782302 DOI: 10.1007/s00467-005-1826-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2004] [Revised: 12/06/2004] [Accepted: 12/08/2004] [Indexed: 11/28/2022]
Abstract
In Japan, the school urinary screening system facilitates early detection and treatment of membranoproliferative glomerulonephritis (MPGN) in childhood. The present study investigated the long-term prognosis in 19 children with diffuse MPGN type I who received steroid therapy. Before signs of glomerulonephritis were confirmed, all patients displayed abnormal urinalysis results, predominantly through school urinary screening. Treatment comprised a regimen of alternate-day prednisolone after steroid pulse or cyclophosphamide therapy, and follow-up was continued for 10-24 years. Excluding 1 patient on short-term therapy, 18 patients received long-term alternate-day prednisolone therapy for 4-12 years. Treatment was discontinued when amelioration was confirmed on renal biopsy. As of the last observation, urinary abnormalities and hypocomplementemia had disappeared in 15 patients, while mild proteinuria without hypocomplementemia remained in 4 patients. No patients required hemodialysis. Moreover, no severe adverse effects attributable to treatment were identified other than mild short stature. Early detection and therapy using pulse methylprednisolone followed by alternate-day prednisolone was thus confirmed as safe and useful for treating diffuse MPGN type I.
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Affiliation(s)
- Takeshi Yanagihara
- Department of Pediatrics, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, 113-8602, Tokyo, Japan.
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Jones G, Juszczak M, Kingdon E, Harber M, Sweny P, Burns A. Treatment of idiopathic membranoproliferative glomerulonephritis with mycophenolate mofetil and steroids. Nephrol Dial Transplant 2004; 19:3160-4. [PMID: 15479745 DOI: 10.1093/ndt/gfh526] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Treatment of adults with idiopathic membranoproliferative glomerulonephritis (IMPGN) is often unrewarding with approximately 60% of patients progressing to end-stage renal failure within 10 years. Although children with IMPGN may respond to steroid therapy, there is no significant benefit to treating adult IMPGN patients with immunosuppression. METHODS Outcome measures in five patients with IMPGN who were treated with oral prednisolone and mycophenolate mofetil (MMF) (treatment group) were compared with six patients with IMPGN who did not receive immunosuppression (control group). RESULTS There was no significant difference between either group in baseline clinical characteristics or systolic and diastolic blood pressure during observation. In the treatment group, there was a significant reduction in proteinuria from a baseline of 5.09 to 1.97 g/24 h (P = 0.003) at 6 months, 1.96 g/24 h (P = 0.003) at 12 months and 2.59 g/24 h (P = 0.015) at 18 months. There was no significant change in proteinuria over 18 months in the control group. Serum creatinine concentration and creatinine clearance did not change significantly over 18 months in the treatment group. In the control group, there were significant changes in serum creatinine and creatinine clearance over 18 months [baseline 103 to 159 micromol/l (P = 0.004) and baseline 108 to 67 ml/min (P > 0.001), respectively] when compared to baseline, although the differences were not significant when the two groups were compared directly. CONCLUSIONS This preliminary study suggests that in the short term, the combination of MMF and prednisolone can significantly reduce proteinuria and may preserve renal function in patients with IMPGN.
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Affiliation(s)
- Gareth Jones
- Centre for Nephrology, Royal Free Hospital, Pond Street, London NW3 2QG, UK.
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Levin A. Management of membranoproliferative glomerulonephritis: evidence-based recommendations. KIDNEY INTERNATIONAL. SUPPLEMENT 1999; 70:S41-6. [PMID: 10369194 DOI: 10.1046/j.1523-1755.1999.07006.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Idiopathic membranoproliferative glomerulonephritis (MPGN) is one of the least common types of GN. This article critically evaluates the literature and generates evidence-based recommendations for the management of idiopathic MPGN. For all age groups, for idiopathic MPGN with normal renal function and asymptomatic nonnephrotic range proteinuria, no specific therapy is necessary (grades B and C). Close follow-up every three to four months, with specific attention to renal function, proteinuria, and blood pressure control, is recommended. In children with MPGN and nephrotic syndrome and/or impaired renal function, a trial of steroids is warranted (grade A). The best data suggest high-dose, alternate-day steroids for a period of 6 to 12 months (40 mg/m2 on alternate days). If no benefit is seen, discontinuation with close follow-up and attention to conservative treatment (that is, blood pressure control, use of agents to reduce proteinuria, and correction of metabolic abnormalities) is recommended. In adults with MPGN, impaired renal function, and/or nephrotic-range proteinuria, a trial of aspirin (325 mg daily), dipyridamole (75 to 100 mg tid), or a combination of the two for 12 months is reasonable (grade B). Again, if no benefits are seen, the treatment should be stopped. Attention to factors known to delay the progression of renal decline and close follow-up should be part of the treatment plan (grades B and C).
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Affiliation(s)
- A Levin
- Division of Nephrology, University of British Columbia, St. Paul's Hospital, Vancouver, Canada.
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Arslan S, Saatci U, Ozen S, Bakkaloğlu A, Besbas N, Tinaztepe K, Hayran M. Membranoproliferative glomerulonephritis in childhood: factors affecting prognosis. Int Urol Nephrol 1998; 29:711-6. [PMID: 9477371 DOI: 10.1007/bf02552190] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
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 immunosuppression therapy should be instituted in patients unresponsive to steroids and that the aforementioned risk factors are higher for the development of renal failure.
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Affiliation(s)
- S Arslan
- Hacettepe University Faculty of Medicine, Ankara, Turkey
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Faedda R, Pirisi M, Satta A, Bosincu L, Bartoli E. Immunosuppressive treatment of Berger's disease. Clin Pharmacol Ther 1996; 60:561-7. [PMID: 8941029 DOI: 10.1016/s0009-9236(96)90152-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
BACKGROUND The aim of our study was to determine whether immunosuppressive treatment is effective in preventing and reversing the evolution of Berger's disease toward chronic renal failure. METHODS We studied 20 unselected, consecutive patients with biopsy-proven Berger's disease who met the criteria for disease progression. They had proteinuria, significant histologic changes, persistent hematuria, and red cell casts. The treatment consisted of prednisone in an alternate-day regimen and cyclophosphamide, either in a daily oral administration or in a monthly intravenous pulse injection, both given for a 6-month cycle. Five patients had chronic renal failure (as disclosed by plasma creatinine of 230 +/- 71 mumol/L), hypertension, and proteinuria (2.7 +/- 0.8 gm/day), whereas the remaining 15 patients had normal renal function (plasma creatinine, 97 +/- 18 mumol/L) and less severe proteinuria (1.9 +/- 1.1 gm/day). However, even these 15 patients had a significant number of risk factors heralding progression to chronic renal failure. RESULTS Over an average follow-up of 8.7 +/- 3.7 years (range, 5 to 15 years), all patients but one had complete disease remission, including five patients with incipient chronic renal failure. Relapse occurred in two patients who were healed after a repeat treatment cycle. Over the entire follow-up period, no patient progressed to chronic renal failure and plasma creatinine concentration remained stable, even in subjects in whom it was high before treatment (257 +/- 79 versus 230 +/- 71 mumol/L; p > 0.05). CONCLUSION The immunosuppressive treatment of patients with Berger's disease with high probability of progression appears to be effective in the prevention of end-stage renal disease.
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Affiliation(s)
- R Faedda
- Istituto di Patologia Medica, University of Sassari, Italy
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Faedda R, Pirisi M, Satta A, Bosincu L, Bartoli E. Regression of Henoch-Schönlein disease with intensive immunosuppressive treatment. Clin Pharmacol Ther 1996; 60:576-81. [PMID: 8941031 DOI: 10.1016/s0009-9236(96)90154-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
OBJECTIVE To assess the results of a new immunosuppressive cycle, which had given favorable results in other immune-mediated glomerulonephritides, in the treatment of Henoch-Schönlein disease. METHODS Eight patients (seven male and one female; age range, 13 to 61 years) with biopsy-proved Henoch-Schönlein were treated with the following protocol: (1) induction with 250 to 750 mg intravenous methylprednisolone every day for 3 to 7 days plus 100 to 200 mg oral cyclophosphamide every day, (2) maintenance with 100 to 200 mg oral prednisone on alternate days plus cyclophosphamide, as before, for 30 to 75 days; (3) tapering, with prednisone reduced on average by 25 mg every month while the cyclophosphamide dose remained the same, and (4) discontinuation, after at least 6 months, with abrupt interruption of cyclophosphamide and slow tapering of prednisone. The results were assessed in terms of remission, improvement, progression of disease, kidney failure, and death, unambiguously defined. The follow-up extended up to 12 years. RESULTS Seven of eight patients had a complete remission that was maintained indefinitely thereafter. Plasma creatinine levels decreased on average from 211 +/- 81 to 92 +/- 27 mumol/L (p < 0.01) and urine protein excretion decreased from 1.9 +/- 0.8 to 0.3 +/- 0.1 gm/day (p < 0.01). One patient died of intestinal infarction caused by atherosclerotic mesenteric artery thrombosis. CONCLUSIONS Our data suggest that an intensive immunosuppressive regimen that combines prednisone and cyclophosphamide at high doses can be effective in healing Henoch-Schönlein disease.
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Affiliation(s)
- R Faedda
- Istituto di Patologia Medica, University of Sassari, Italy
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Abstract
Disorders of glomerular structure and function are encountered frequently in clinical medicine. Many arise as part of a well-defined multisystem or multi-organ disease process, while in others the clinical and laboratory manifestations are consequent to the sole or predominant involvement of glomeruli. The latter are known as the primary glomerulopathies. These disorders can evoke a variety of clinical syndromes, including acute glomerulonephritis, rapidly progressive glomerulo-nephritis, nephrotic syndrome, "symptomless" hematuria and/or proteinuria, and chronic glomerulonephritis. The identification of underlying morphology, through the application of renal biopsy techniques, can provide useful information for both prognosis and treatment. Pathogenic mechanisms involved in the primary glomerulopathies are varied, but immunologic perturbations underlie many disease entities. This article describes the clinical features, pathology, natural history, and treatment of the main categories of primary glomerulonephritis, with emphasis on recent developments and practical aspects of diagnosis and management.
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Affiliation(s)
- R J Glassock
- Department of Internal Medicine, University of Kentucky College of Medicine, Lexington, USA
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Schwertz R, de Jong R, Gretz N, Kirschfink M, Anders D, Schärer K. Outcome of idiopathic membranoproliferative glomerulonephritis in children. Arbeitsgemeinschaft Pädiatrische Nephrologie. Acta Paediatr 1996; 85:308-12. [PMID: 8695987 DOI: 10.1111/j.1651-2227.1996.tb14022.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
The aim of this multicentre study was to analyse the long-term outcome of idiopathic membranoproliferative glomerulonephritis (MPGN) according to histological type and to the presence of C3 nephritic factor. Fifty patients aged 2-14 years at the onset of the study were followed over 2-20 years; 26 patients had MPGN type I, 17 had type II and 7 had type III. Treatment was variable. At the last observation, 30 patients had reached terminal and four pre-terminal renal failure. The median survival probability until renal death was 15.3, 8.7 and 15.9 years for disease types I, II and III respectively (difference between MPGN types I + III versus type II: p = 0.013). The presence of an initial nephrotic syndrome was associated with a more rapid progression (p = 0.018). C3 nephritic factor was of no prognostic value. We conclude that the outcome of MPGN mainly depends on the histological type observed.
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Affiliation(s)
- R Schwertz
- Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany
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Bergstein JM, Andreoli SP. Response of type I membranoproliferative glomerulonephritis to pulse methylprednisolone and alternate-day prednisone therapy. Pediatr Nephrol 1995; 9:268-71. [PMID: 7632508 DOI: 10.1007/bf02254181] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Sixteen children with biopsy-confirmed type I membranoproliferative glomerulonephritis (MPGN) were treated with six alternate-day intravenous pulses of methylprednisolone followed by single-dose alternate-day prednisone for 12-66 months (mean 37 months). The average length of follow-up was 52 months (range 12-127 months). Compared with pretreatment values, the frequency of hematuria (13/16 vs. 8/16, P < 0.05) and the levels of serum albumin (2.66 +/- 0.69 vs. 3.76 +/- 0.39 g/dl, P < 0.001), creatinine clearance (97 +/- 37 vs. 129 +/- 26 ml/min/1.73 m2, P < 0.001), and proteinuria (5.2 +/- 5.1 vs. 1.0 +/- 0.8 g/day, P < 0.001) were significantly improved after 3 months of therapy. Improvement has persisted through the end of the follow-up period. Repeat kidney biopsies showed a significant reduction in acute changes but an increase in chronic changes. Thirteen patients have been off therapy from 1 to 74 months (mean 20.8 months). Nine have a normal urinalysis, creatinine clearance, and protein excretion. The remainder have normal renal function but proteinuria ranging from 3.2 to 4.3 g/day. The data support the evidence of other investigators that corticosteroid therapy is beneficial in type I MPGN and suggest that initiation with pulse methylprednisolone may promote early stabilization of the disease.
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Affiliation(s)
- J M Bergstein
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, USA
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