Treatment Of Membranous Nephropathy Research Articles

Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety

Background: To observe effectiveness and renal safety of long-term low-dose cyclosporine in idiopathic membranous nephropathy (IMN).Methods: Sixty-eight patients were enrolled in this prospective cohort study. Renal endpoint was defined as a decrease in eGFR ≥50% from baseline and a development of eGFR ≤60 ml/min/1.73m2.Results: A cyclosporine dose of 2.0 ± 0.5 mg/kg/d and a prednisone of 0.3 ± 0.2 mg/kg/d were prescribed. The duration of cyclosporine treatment was 27 (3–80) months. The overall remission rate was 91% with a relapse rate of 42%. Fourteen patients had cyclosporine-related acute renal injury (CsA-ARI) within the first three months, and 16 patients had cyclosporine related chronic renal injury (CsA-CRI) within the first year. At the end of follow-up (50 ± 18 months), 16 patients (24%) reached renal endpoint. Presence of intimal fibrosis of small artery and higher time-averaged proteinuria were identified as independent risk factors for renal endpoint. RAS inhibition treatment decreased the risk of poor renal outcome. Patients in CsA-ARI group had the highest proteinuria at the third month, the highest time-average proteinuria and the highest proportion of cases reaching renal endpoint. Patients with CsA-CRI were of the oldest age and with the lowest baseline eGFR.Conclusions: Low-dose cyclosporine is effective in treating IMN. CsA-ARI and no response in proteinuria during the first three months of cyclosporine treatment had the lowest benefit/risk ratio, and these patients should be switched to non-calcineurin-inhibitor based regimen. Patients of older age, with lower baseline eGFR, or having intimal sclerosis of small artery, are more likely to develop progressive renal dysfunction.

Treatment of membranous nephropathy with mizoribine: A control trial

AimMembranous nephropathy remains the most common form of the nephrotic syndrome in adults. The combination therapy of steroid and cyclophosphamide has routinely been used. Although satisfactory therapeutic efficacy can be achieved, its side effect on reproductive system has been a concern. Mizoribine is an imidazole nucleoside and a novel immunosuppressant that has been used to treat other immune-related diseases. In this study we examine if the combined regimen of mizoribine and steroid would be advantageous over the use of cyclophosphamide and steroid in treating adult membranous nephropathy. MethodsThere were total of fifty-five patients completed the study. These patients had membranous nephropathy with presentation of proteinuria. They were treated with combined regimen of mizoribine and steroid or cyclophosphamide and steroid, and were followed up for one year to monitor safety and efficacy. ResultsWe found the condition of proteinuria was significantly improved in the mizoribine group and the improvement was comparable to the patients treated with cyclophosphamide. These patients also exhibited an increase of serum albumin. There was no significant increase of adverse events with the use of mizoribine-based therapy, suggesting the tolerability of mizoribine in adult patients with membranous nephropathy. ConclusionIn conclusion, the results indicated the satisfactory safety and efficacy of the combination regiment of mizoribine and steroid in treating adult patients with membranous nephropathy.

Idiopathic membranous nephropathy: Evolution in understanding the problem

The review highlights the evolution of ideas on the. mechanisms responsible for the 'development of membranous nephropathy(MN), glomerulopathy that is the most common cause of nephrotic syndrome in adults. Primary emphasis is placed on the primary form of MN. The important step to understanding the nature of this clinical and morphological form of glomerulonephritis is to create its animal model (Heymann nephritis), then to decipher the mechanisms of immune complex damage (complement activation,a role of cellular immunity), and to identify autoantigens responsible for the development of idiopathic MN in man (podocyteneutral endopeptidase, transmembrane M-type phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A. The findings constituted the basis for developing current methods for the diagnosis and treatment of MN, including the pathogenetically sound inhibition of autoantibody production, as well as a molecular orientation effect on podocyte dysfunction.

Resveratrol ameliorates renal damage, increases expression of heme oxygenase-1, and has anti-complement, anti-oxidative, and anti-apoptotic effects in a murine model of membranous nephropathy.

BackgroundIdiopathic membranous nephropathy (MN) is an autoimmune-mediated glomerulonephritis and a common cause of nephrotic syndrome in adults. There are limited available treatments for MN. We assessed the efficacy of resveratrol (RSV) therapy for treatment of MN in a murine model of this disease.MethodsMurine MN was experimentally induced by daily subcutaneous administration of cationic bovine serum albumin, with phosphate-buffered saline used in control mice. MN mice were untreated or given RSV. Disease severity and pathogenesis was assessed by determination of metabolic and histopathology profiles, lymphocyte subsets, immunoglobulin production, oxidative stress, apoptosis, and production of heme oxygenase-1 (HO1).ResultsMN mice given RSV had significantly reduced proteinuria and a marked amelioration of glomerular lesions. RSV also significantly attenuated immunofluorescent staining of C3, although there were no changes of serum immunoglobulin levels or immunocomplex deposition in the kidneys. RSV treatment of MN mice also reduced the production of reactive oxygen species (ROS), reduced cell apoptosis, and upregulated heme oxygenase 1 (HO1). Inhibition of HO1 with tin protoporphyrin IX partially reversed the renoprotective effects of RSV. The HO1 induced by RSV maybe via Nrf2 signaling.ConclusionOur results show that RSV increased the expression of HO1 and ameliorated the effects of membranous nephropathy in a mouse model due to its anti-complement, anti-oxidative, and anti-apoptotic effects. RSV appears to have potential as a treatment for MN.

HIV Infection with Membranous Nephropathy in a Low HIV Prevalent Muslim Country, Bangladesh: A Case Report

The most common renal manifestation of Human immunodeficiency virus (HIV), is HIV associated nephropathy (HIVAN). In this report, we describe a case that was referred for evaluation of proteinuria. Diagnostic workup revealed HIV infection with membranous nephropathy (MN). As he had sub-nephrotic range proteinuria and normal renal function we did not start any treatment for membranous nephropathy and for anti-retroviral therapy he was sent to a referral center. Being an uncommon variety of nephropathy in HIV infected patient in one of the lowest HIV prevalent country, we are reporting the case.DOI: http://dx.doi.org/10.3329/jom.v16i1.22408 J MEDICINE 2015; 16 : 61-63

Membranous nephropathy: a review on the pathogenesis, diagnosis, and treatment.

In adults, membranous nephropathy (MN) is a major cause of nephrotic syndrome. However, the etiology of approximately 75% of MN cases is idiopathic. Secondary causes of MN are autoimmune diseases, infection, drugs, and malignancy. The pathogenesis of MN involves formation of immune complex in subepithelial sites, but the definite mechanism is still unknown. There are three hypotheses about the formation of immune complex, including preformed immune complex, in situ immune-complex formation, and autoantibody against podocyte membrane antigen. The formation of immune complex initiates complement activation, which subsequently leads to glomerular damage. Recently, the antiphospholipase A2 receptor antibody was found to be associated with idiopathic MN. This finding may be useful in the diagnosis and prognosis of MN. The current treatment includes best supportive care, which consists of the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, lipid-lowering agents, and optimal control of blood pressure. Immunosuppressive agents should be used for patients who suffer from refractory proteinuria or complications associated with nephrotic syndrome. Existing evidence supports the use of a combination of steroid and alkylating agents. This article reviews the epidemiology, pathogenesis, diagnosis, and the treatment of MN.

A Case of Bad Prognosis for Membranous Nephropathy in a Patient with Mixed Connective Tissue Disease

Incidence of renal involvement in mixed connective tissue disease (MCTD) is low. In the presence of glomerulonephritis, membranous nephropathy (MN) in MCTD is common. A 47-year-old woman presented with hypothyroidism. She developed Raynaud’s phenomenon, arthralgia, and incomplete lupus erythematosus, diagnosed with MCTD. One year after then, the patient developed persistent proteinuria (1+) without hematuria. Following diagnosis with MCTD, her renal function began to deteriorate. The renal biopsy showed late stage MN. For the treatment of MN with mild proteinuria and MCTD, we prescribed an angiotensin II receptor blocker and 7.5 mg of methotrexate per week and 300 mg of hydroxychloroquine daily. The patient had a reduced estimated glomerular filtration rate of 55% for the subsequent eight years. The MN in MCTD is known to show good renal prognosis. Here, we report on a rare case of MN in MCTD in Korea with a bad prognosis. (J Rheum Dis 2015;22:260262)

Membranous nephropathy with repeated flares in IgG4-related disease.

IgG4-related disease (IgG4-RD) is associated with the infiltration of IgG4-positive plasma cells into various organs. Nephropathy of IgG4-RD is generally interstitial nephritis and glomerulonephritis is rare. We describe a case of membranous nephropathy (MN) without interstitial nephritis associated with IgG4-RD symptoms including lymphadenopathy and pulmonary and pleural lesions. Treatment with steroids improved these clinical symptoms, but withdrawal of steroids induced the repeated relapse of MN. Finally, flaring of MN was prevented by the combination of steroids and cyclosporine. This is the first report of the successful treatment of MN associated with IgG4-RD by this combination therapy.

Treatment of membranous nephropathy in patients with renal insufficiency: what regimen to choose?

Treatment of membranous nephropathy in patients with renal insufficiency: what regimen to choose?

Rituximab: emerging treatment strategies of immune-mediated glomerular disease

The use of monoclonal antibodies in the treatment of malignancy and autoimmune diseases has rapidly expanded in the last decade. Rituximab, a monoclonal antibody to the CD20 antigen on B cells, was first approved by the US FDA in 1997 to treat non-Hodgkin’s B-cell lymphoma. It is now used, however, for a variety of diseases in both on- and off-label uses. It was approved by the FDA for use in refractory rheumatoid arthritis in 2007, and in April 2011 it was approved for the treatment of anti-neutrophil cytoplasmic antibody-associated vasculitides (including granulomatosis with polyangiitis [Wegener’s granulomatosis] and microscopic polyangiitis), based on the promising results of the RAVE trial. Within the field of nephrology, in addition to its use in anti-neutrophil cytoplasmic antibody-associated vasculitides, it is has been used in the treatment of membranous nephropathy, membranoproliferative glomerulonephritis and lupus nephritis.

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Treatment of Hepatitis B Virus-Associated Membranous Nephropathy: Lamivudine Era versus Post-Lamivudine Era

Triggers, Bullets and Targets, Puzzle of Membranous Nephropathy

IntroductionIdiopathic Membranous Nephropathy (MN) is a common cause of adult nephrotic syndrome. Recently, M-type phospholipase A2 receptor (PLA2-R) has been discovered as the main podocyte antigen in the pathogenesis of idiopathic MN.Materials and MethodsIn this mini review, the author searched English-language MEDLINE for the terms “membranous nephropathy”, “rituximab”, and “phospholipase A2 receptor” up to October 2011.ResultsIn support of its earlier discovery, reports from China and Europe confirmed the major pathogenic role of non-complement fixing IgG4 antibody against PLA2-R in the pathogenesis of idiopathic MN. Antibodies against aldose reductase (AR) and manganese superoxide dismutase (SOD2 ), and sub-epithelial deposition of cationic bovine serum albumin (BSA) are also reported in rare occasions. It seems that Rituximab is a good therapeutic choice for those patients who need immunosuppressive therapy.ConclusionsGreat discoveries in the diagnosis and treatment of idiopathic MN have been performed but pathogenic mechanism and triggers for anti-PLA2-R production are still unknown.

Astragaloside IV Attenuates Complement Membranous Attack Complex Induced Podocyte Injury Through the MAPK Pathway

Membranous nephropathy (MN) is the most common cause of idiopathic nephrotic syndrome in adults and the cause is known to be due to the injury of podocytes located in the glomeruli. Astragalus membranaceus has been used for the treatment of patients with MN in China for a long time. The beneficial effect of Astragalus membranaceus on proteinuria of patients with MN has been well documented. However, the mechanism of astragalus membranaceu in alleviation of MN is still not completely understood. Therefore, in the current study, we employed a podocyte injury model induced by complement membranous attack complex to examine the mechanism of astragalus membraneceus in the treatment of MN. We found that complement membranous attack complex could increase lactate dehydrogenase (LDH) release from podocytes and astragaloside IV (AS-IV) could prevent LDH release from podocytes in a time- and dose-dependent pattern. Moreover, AS-IV restored podocyte morphology and cytoskeleton loss induced by complement membranous attack complex. Furthermore, AS-IV was able to reduce phosphorylation of JNK and ERK1/2 induced by complement membranous attack complex. In conclusion, the mechanism of Astragalus membranaceus in the treatment of MN may be related to its attenuation of podocyte injury through regulation of cytoskeleton and mitogen activated protein kinase.

Membranöse Glomerulonephritis - Pathogenese und Therapie

Membranous nephropathy is the leading cause of the nephrotic syndrome in adults. The diagnosis of idiopathic membranous nephropathy can be made in 70-80 % of the cases. In the other cases, a secondary cause, such as malignancies, lupus erythematodes, virus hepatitis or medication can be found. The idiopathic membranous nephropathy has an autoimmune pathogenesis in which the recently discovered phospholipase A 2 receptor antibody possibly plays a central role. The symptomatic treatment of membranous nephropathy consists of ACE-inhibitors and/or ATI-blockers, which are helpful in treating proteinuria. An immunosuppressive medication should be started if there are risk factors for loss of renal function, large proteinuria (> 8 g/24 h) or renal function deterioration. The most extensive data exist on the treatment with alkylating agents or ciclosoporine A. The role of new treatment options such as rituximab is being currently investigated.

Therapeutic Effect of the Impatiens balsamina Linne Extract on the Membranous Nephropathy

Objective : Membranous nephropathy(MN) is one of the most common causes of nephrotic syndrome in adults. MN has been defined as granular subepithelial deposition of IgG immune complexes along the glomerular basement membrane(GBM). However, there is not a satisfactory treatment for MN. We aimed to identify the effect of Impatiens balsamina Linne(IBL) treatment on cationic bovine serum albumin(cBSA)-induced MN in a mouse model. Methods : Mice were divided into 4 groups. The normal group was injected with saline. The Control group was treated with cBSA(50 mg/kg i.p) only. The third group IBL-100, was treated with cBSA(50 mg/kg, i.p) and IBL(100 mg/kg, p.o). The fourth group IBL-400, was treated with cBSA(50 mg/kg, i.p) and IBL (400 mg/kg, p.o). After cBSA and IBL treatment for 6 weeks, we measured change of body weight, proteinuria, serum albumin, total cholesterol, triglyceride, BUN, creatinine, IgA, IgM, IgG, TNF-, IL-6 and IL- levels. The morphologic changes of renal glomeruli were also observed with a light microscope. Results : The level of proteinuria significantly decreased and serum albumin increased in groups treated with cBSA and IBL extract compared with the control. The levels of serum triglyceride, BUN, IgG, TNF-, IL- significantly decreased in both IBL groups. In histological findings of kidney tissue, thickening of GBM decreased in both IBL groups. Conclusions : This study shows that IBL might be effective for treatment of acute stage MN. More clinical data and studies are to be done for efficient application.

Steroid treatment in patients with membranous nephropathy and hepatitis B virus surface antigenemia: a report of two cases

Although the clinical benefits of antiviral treatment in the management of membranous nephropathy (MN) in patients with chronic hepatitisB virus (HBV) infection have been suggested, it should be evaluated more carefully. In this report, we present two cases with quiescent HBV who were administered lamivudine for either the initial treatment of MN or to control the reactivation of HBV during treatment with corticosteroids. No clinical benefit of lamivudine as an initial treatment was observed in one patient, which obliged us to commence administration of prednisolone (PSL). On the other hand, lamivudine seemed to play a pivotal role in the remission of an acute exacerbation of hepatitisB during treatment with PSL and mizoribine in the other patient. These two patients seemed to tolerate administration of PSL with or without an immunosuppressive agent well, since gradual and prompt improvements of nephrotic status were confirmed within a few months, thus suggesting the potential benefit of steroid treatment. There is little consensus regarding the optimal choice of steroids and immunosuppressants for the treatment of MN with chronic HBV infection, due to the potential for stimulation of viral replication and precipitation of hepatic flares. Our observations, however, suggest that treatment with PSL still should be reserved for quiescent HBV carriers with MN. Further studies will be required to determine the optimal timing and appropriate duration of antiviral treatment in such patients requiring long-term immunosuppression.

Cytochrome P450 2B1 Mediates Complement-dependent Sublytic Injury in a Model of Membranous Nephropathy

Membranous nephropathy is a disease that affects the filtering units of the kidney, the glomeruli, and results in proteinuria accompanied by loss of kidney function. Passive Heymann nephritis is an experimental model that mimics membranous nephropathy in humans, wherein the glomerular epithelial cell (GEC) injury induced by complement C5b-9 leads to proteinuria. We examined the role of cytochrome P450 2B1 (CYP2B1) in this complement-mediated sublytic injury. Overexpression of CYP2B1 in GECs significantly increased the formation of reactive oxygen species, cytotoxicity, and collapse of the actin cytoskeleton following treatment with anti-tubular brush-border antiserum (anti-Fx1A). In contrast, silencing of CYP2B1 markedly attenuated anti-Fx1A-induced reactive oxygen species generation and cytotoxicity with preservation of the actin cytoskeleton. Gelsolin, which maintains an organized actin cytoskeleton, was significantly decreased by complement C5b-9-mediated injury but was preserved in CYP2B1-silenced cells. In rats injected with anti-Fx1A, the cytochrome P450 inhibitor cimetidine blocked an increase in catalytic iron and ROS generation, reduced the formation of malondialdehyde adducts, maintained a normal distribution of nephrin in the glomeruli, and provided significant protection at the onset of proteinuria. Thus, GEC CYP2B1 contributes to complement C5b-9-mediated injury and plays an important role in the pathogenesis of passive Heymann nephritis.

Recurrent Idiopathic Membranous Nephropathy: Early Diagnosis by Protocol Biopsies and Treatment with Anti-CD20 Monoclonal Antibodies

Membranous nephropathy (MN) recurs posttransplant in 42% of patients. We compared MN recurrence rates in a historical cohort transplanted between 1990 and 1999 and in a current cohort diagnosed by protocol biopsies, we analyzed the progression of the disease and we assessed the effects of anti-CD20 antibodies (Rituximab) on recurrent MN. The incidence of recurrent MN was similar in the historical (53%) and the current cohorts (41%), although in the later the diagnosis was made earlier (median, 4[2-21] months vs. 83[6-149], p = 0.002) and the disease was clinically milder. Twelve out of 14 patients (86%) with recurrent MN in the current cohort had progressive increases in proteinuria. Eight recipients were treated with Rituximab after their proteinuria increased from median, 211 mg/day (64-4898) at diagnosis to 4489 (898-13 855) (p = 0.038). Twelve months post-Rituximab, 75% of patients had either partial (PR) or complete remission (CR). After 24 months 6/7 (86%) had PR/CR and one patient relapsed. Posttreatment biopsies showed resorption of electron dense immune deposits in 6/7 cases and were negative for C3 (4/7) and IgG (3/7). Protocol biopsies allow early diagnosis of subclinical recurrent MN, which is often progressive. Treatment of recurrent MN with Rituximab is promising and should be evaluated in a prospective randomized controlled trial.

Rituximab Therapy for Membranous Nephropathy

The treatment of membranous nephropathy (MN) remains controversial. Rituximab, which selectively targets B cells, has emerged as a possible alternative treatment option with limited toxicity. The available data on rituximab therapy for MN were reviewed using the MEDLINE database (inception to August 1, 2008), Google Scholar, and selected reference lists. English-language studies investigating the use of rituximab in idiopathic and secondary MN, in native and transplanted kidneys, were included. Study design, subject number, clinical characteristics (diagnosis, previous and concomitant treatment courses, baseline proteinuria, baseline renal function), rituximab protocol, follow-up period, achievement of complete or partial remission, changes in proteinuria and renal function, and adverse effects of therapy were extracted. Twenty-one articles were included for review; all were either case reports or case series without controls. More than half of the published cases (50 of 85) came from one center where rituximab was used as primary immunosuppression for idiopathic MN. The available data suggest that rituximab, dosed either as 375 mg/m(2) once weekly for 4 wk or as 1 g on days 1 and 15, achieves a 15 to 20% rate of complete remission and a 35 to 40% rate of partial remission. The drug was well tolerated with minimal adverse events. Although rituximab may prove to be a better treatment option for MN than alkylating agents or calcineurin inhibitors, the current literature only supports using the drug in research protocols. Whether, when, how, and why to use rituximab in MN remains to be determined.

Symptomatic therapy is the cornerstone of membranous nephropathy treatment in the elderly, with immunosuppressive therapy reserved for high-risk patients

Symptomatic therapy is the cornerstone of membranous nephropathy treatment in the elderly, with immunosuppressive therapy reserved for high-risk patients