mycophenolic-acid and Glomerulonephritis--Membranous

Idiopathic membranous nephropathy (IMN), a common pathological type of nephrotic syndrome, is one of the main causes of kidney failure. With an increasing prevalence, IMN has received considerable attention in China. Based on recent studies, we discuss advances in the diagnosis of IMN and the understanding of its genetic background. Although the pathogenesis of IMN remains unclear, our understanding has been substantially enhanced by the discovery of new antigens such as phospholipase A2 receptor, thrombospondin type-1 domain-containing 7A, exostosin1/exostosin2, neural epidermal growth factor-like 1 protein, neural cell adhesion molecule 1, semaphorin 3B, and factor H autoantibody. However, due to ethnic, environmental, economic, and lifestyle differences and other factors, a consensus has not yet been reached regarding IMN treatment. In view of the differences between Eastern and Western populations, in-depth clinical evaluations of biomarkers for IMN diagnosis are necessary. This review details the current treatment strategies for IMN in China, including renin-angiotensin system inhibitors, corticosteroid monotherapy, cyclophosphamide, calcineurin inhibitors, mycophenolate mofetil, adrenocorticotropic hormone, and traditional Chinese medicine, as well as biological preparations such as rituximab. In terms of management, the 2012 Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines do not fully consider the characteristics of the Chinese population. Therefore, this review aims to present the current status of IMN diagnosis and treatment in Chinese patients, and includes a discussion of new approaches and remaining clinical challenges.

Topics: Adrenal Cortex Hormones; Autoantibodies; Biomarkers; Calcineurin Inhibitors; China; Glomerulonephritis, Membranous; Humans; Kidney; Mycophenolic Acid; Nephrotic Syndrome

In the last 10 years, basic science and clinical research have made important contributions to the understanding and management of primary membranous nephropathy (MN). The identification of antibodies directed against the M-type phospholipase A

Topics: Adrenal Cortex Hormones; Adrenocorticotropic Hormone; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Immunological; Autoantibodies; Calcineurin Inhibitors; Chlorambucil; Cyclophosphamide; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prognosis; Receptors, Phospholipase A2; Rituximab

Amelioration of podocyte injury, which can lead to podocyte detachment, is the target of therapeutic intervention in glomerular diseases. Since podocytes are terminally differentiated cells with little or no proliferative ability, their loss results in permanent glomerular dysfunction. In immune-mediated glomerular diseases, a variety of immunomodulatory agents are used to maintain podocytes by systemic immunosuppression, which indirectly ameliorates podocyte injury by interrupting the input of immunological stress. However, in contrast to the indirect therapeutic strategy mediated by immunosuppression, recent data now suggest that immunomodulatory agents directly act on podocytes in an agent-dependent manner. Indeed, the therapeutic efficacy of immunomodulatory agents is, at least in part, derived by the direct action on podocytes. In this review, we discuss the molecular targets and mechanisms by which immunomodulatory agents alleviate podocyte injury and examine their clinical significance.

Topics: Abatacept; Adjuvants, Immunologic; Calcineurin Inhibitors; Everolimus; Glomerulonephritis; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Levamisole; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Podocytes; Ribonucleosides; Rituximab; Sirolimus; Tacrolimus; TOR Serine-Threonine Kinases

Glomerular diseases historically have been challenging disorders to comprehend and treat for patients and physicians alike. Kidney biopsy is the gold standard of diagnosis, but the link between pathophysiology and the histologic representation of kidney injury has remained elusive in many of these diseases. As a result, treatment of glomerular disease usually involves therapies that are not specific to disease pathogenesis, such as blockade of the renin-angiotensin-aldosterone system and various immunosuppression regimens. Recent research has resulted in greater insight into some glomerular diseases, leading to the hope that new diagnostic tests and treatments targeting disease-specific mechanisms are on the horizon. We review recent progress on the understanding, diagnosis, and treatment of 4 glomerular diseases: immunoglobulin A nephropathy, focal segmental glomerulosclerosis, the C3 glomerulopathies, and idiopathic membranous nephropathy.

Topics: Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Complement C3; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Mycophenolic Acid; Randomized Controlled Trials as Topic; Rituximab

Exciting progress recently has been made in our understanding of idiopathic membranous nephropathy, as well as treatment of this disease. Here, we review important advances regarding the pathogenesis of membranous nephropathy. We will also review the current approach to treatment and its limitations and will highlight new therapies that are currently being explored for this disease including Rituximab, mycophenolate mofetil, and adrenocorticotropic hormone, with an emphasis on results of the most recent clinical trials.

Topics: Adrenocorticotropic Hormone; Alkylating Agents; Antibodies, Monoclonal, Murine-Derived; Calcineurin Inhibitors; Clinical Trials as Topic; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Mycophenolic Acid; Receptors, Phospholipase A2; Rituximab

Idiopathic membranous nephropathy (IMN) is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.. To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.. PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs) meeting the criteria was performed using Review Manager.. 17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008), partial or complete remission (effective) (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003), and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC) was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX), leflunomide (LET) showed no beneficial effect, mycophenolate mofetil (MMF) showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006) but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15).. This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

Topics: Adult; Alkylating Agents; Calcineurin Inhibitors; China; Chlorambucil; Clinical Trials as Topic; Cyclophosphamide; Cyclosporine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Isoxazoles; Leflunomide; Male; Middle Aged; Mycophenolic Acid; Remission Induction; Tacrolimus

Membranous nephropathy, focal segmental glomerulosclerosis and IgA nephropathy are the most commonly recognized types of primary glomerulonephritis that progress to end-stage renal disease. Persistent proteinuria is a major determinant of such progression. Reduction of proteinuria slows progression of renal disease and improves renal survival, but many of the agents used to reduce proteinuria carry a considerable risk of toxicity. The assessment of benefit versus risk of these medications can be further complicated by the temporal disconnect between the onset of benefit and of serious adverse events. In addition, relapses are common in these disorders and there is often a need for retreatment. Such retreatment might lead to repeated and/or prolonged drug exposure and to the oversight or underestimation of the cumulative dose of these agents because of the potentially extended interval between relapses. Consequently, it is very important to constantly review each patient's status and take into account their age, comorbid conditions and cumulative drug exposure when assessing treatment options. The potentially delayed development of adverse events also emphasizes the need for long-term surveillance of patients who receive immunosuppressive treatment for glomerular disease, often well beyond their drug exposure period and even when the treatment has been successful.

Topics: Alkylating Agents; Calcineurin Inhibitors; Glomerulonephritis; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Proteinuria; Remission Induction; Risk Factors

Mycophenolate mofetil is an immunosuppressive agent that blocks purine biosynthesis, inhibits T and B-lymphocyte and mesangial proliferation. Mycophenolate mofetil is not nephrotoxic like calcineurin inhibitors and is widely used in solid-organ transplantation. Recently, mycophenolate mofetil has been introduced in the treatment of autoimmune diseases and primary glomerulopathies. This review analyzes the literature currently available on the treatment of primary glomerulopathies with mycophenolate mofetil. Encouraging results have been obtained in minimal change nephropathy where it may help to reduce the use of steroids in these patients who are often very young. The results obtained in medium and high risk patients with focal segmental glomerulonephritis and idiopathic membranous nephropathy were less encouraging. Conflicting results have been reported on IgA nephropathy in controlled trials. None of these studies attained level A evidence, meaning that randomized control trials of sufficient statistical significance are necessary to estimate the real effectiveness of mycophenolate mofetil in primary glomerulopathies.

Topics: Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid

Topics: Anti-Glomerular Basement Membrane Disease; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Diseases; Lupus Nephritis; Mycophenolic Acid; Nephrosis, Lipoid; Vasculitis

Thirty to forty percent of patients with idiopathic membranous nephropathy have persistent heavy proteinuria and may progress to end-stage kidney disease in 5 - 15 years. The ideal treatment for these patients is a matter of debate. Several nonspecific immunosuppressive regimens have been suggested with the aim of reducing proteinuria and to improve outcome, but all are burdened by significant toxicity. Therefore, more specific and less toxic therapies are needed. Promising results have been recently obtained with rituximab, a monoclonal antibody against the CD20 antigen of B lymphocytes that is able to deplete these cells and, thus, neoformation of pathogenetic antibodies. Other novel drugs, such as adrenocorticotropic hormone, mycophenolate mofetil and eculizumab have been proposed. This paper reviews the safety/efficacy profile of various agents that have been proposed as therapy for this disease, with particular focus on the latest, more specific and hypothesis-driven approaches.

Topics: Adrenocorticotropic Hormone; Alkylating Agents; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antigens, CD20; Calcineurin Inhibitors; Glomerulonephritis, Membranous; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Proteinuria; Rituximab

Approximately two-third of the cases of the adult nephrotic syndrome is caused by a primary glomerular disease, while the remaining one-third is caused by diabetes mellitus, autoimmune diseases, or amyloidosis. There are two different therapies to treat the syndrome: a general and a special treatment. The general treatment includes administering an appropriate diet (reduced intake of proteins and salt), use of diuretics and lipid-lowering drugs (primarily statins) and initiation of anticoagulant treatment, if required. It is generally necessary to administer angiotensin-convertase-enzyme inhibitors and angiotensin receptor blockers as well as initiate a symptomatic treatment to mitigate the loss of special binding-proteins. The special treatment involves the administration of immunosuppressive and cytostatic drugs. This therapy can be initiated only after the evaluation of renal histology and the overall risk status of the patient. Steroids are still the basic immunosuppressive drugs. Their use can be supplemented with other immunosuppressive or cytostatic treatment. In therapy resistant cases, however, new drugs like mycophenolate mofetil or rituximab can also be applied.

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Anticoagulants; Antineoplastic Agents; Diet, Sodium-Restricted; Dietary Proteins; Diuretics; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Hypolipidemic Agents; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Rituximab

Progress in understanding the pathogenesis and treatment of rheumatologic and glomerular diseases such as systemic lupus erythematosus and particularly lupus nephritis has been closely linked with the development of newer immunosuppressive agents. With improved patient survival following the institution of cyclophosphamide and corticosteroid therapy, longer-term management issues came to the forefront, especially how to decrease adverse effects of the immunosuppressive regimen. Many of the immunosuppressive regimens used in lupus patients were first established as efficacious and safe through their use in solid organ transplantation. Mycophenolate mofetil (MMF) is now widely used in the field of transplantation. Following anecdotal reports describing benefits of MMF in lupus and lupus nephritis patients, small studies and finally large randomized, controlled trials have established the use of MMF in these patients, particularly those with lupus nephritis. MMF use in other rheumatologic and renal diseases has been evaluated in only smaller studies and very few randomized controlled trials. Nevertheless, many studies currently are ongoing with this immunosuppressive agent. This article will review the published data and the experience of two major New York medical centers with the use of MMF in autoimmune and renal diseases.

Topics: Acute Disease; Autoimmune Diseases; Clinical Trials as Topic; Glomerulonephritis, IGA; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Granulomatosis with Polyangiitis; Humans; Immunosuppression Therapy; Kidney Diseases; Lupus Nephritis; Mycophenolic Acid; Nephritis, Interstitial

Membranous nephropathy (MN) is a frequent cause of nephrotic syndrome in adults. A considerable diversity of prognosis is seen with idiopathic MN. We overview the recent progress of clinicopathological research, especially the initial factors affecting the longterm outcome of idiopathic MN. We studied retrospectively 105 patients with idiopathic MN and could assign the patients to two different groups based on the electron microscopic (EM) findings. In the homogeneous type only one patient developed end-stage renal failure, and earlier remission occurred in this group. With regard to secondary outcome, increased age, focal segmental glomerular sclerosis, arteriolosclerosis, heterogeneous type of EM findings were independent risk factors. Our results suggest that a new EM classification at initial biopsy is an independent indicator of prognosis in human idiopathic MN.

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Glomerulonephritis, Membranous; Humans; Immunoglobulin G; Immunosuppressive Agents; Kidney Glomerulus; Microscopy, Electron; Mycophenolic Acid; Nephrotic Syndrome; Prognosis; Retrospective Studies; Risk Factors; Rituximab

Idiopathic membranous nephropathy (IMN) remains one of the most common causes of the nephrotic syndrome (NS) in adults. Although the natural history is extremely variable, approximately two thirds of the patients will have persistent high-grade proteinuria and/or develop renal failure over a decade of observation. On the other hand, the remaining third of patients will remit spontaneously and potentially toxic therapy should be avoided in this group. Our capacity to predict which patient will progress at an early stage of the disease has improved substantially in the past 10 years. We present the data from studies of cyclosporine (CSA) and mycophenolate mofetil (MMF) treatment of IMN with their level of evidence in support of efficacy. In addition, based on data related to predicting prognosis, we assign a risk for progression category to the trial patients at entry into these studies. The data are presented in this format so the reader will be able to better discern the risk benefit of treatment within each category and the rationale for our subsequent grade of recommendation for the use of these agents in IMN. CSA has been shown in randomized controlled trials in both the medium and high risk of progression categories of IMN patients to improve proteinuria and preserve renal function at least in the short term in up to two thirds of patients. Other studies suggest prolonged therapy beyond 6 months to 1 year may reduce the high relapse rate after CSA treatment supporting more long-term, continuous, or combination therapy in IMN treatment. The data in favor of MMF treatment of this disease is much weaker and are derived from pilot studies. Only one report applied MMF specifically to IMN patients. In these medium to high risk of progression patients, approximately one-half had a 50% reduction in their baseline proteinuria without a significant alteration in their serum creatinine level. MMF's role as a single agent or as adjunctive therapy in the treatment of IMN needs more rigorous evaluation.

Topics: Cyclosporine; Disease Progression; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Risk Factors

Tacrolimus (TAC) is effective in treating membranous nephropathy (MN); however relapses are frequent after treatment cessation. We conducted a randomised controlled trial to examine whether the addition of mycophenolate mofetil (MMF) to TAC would reduce relapse rate.. Forty patients with biopsy proven idiopathic MN and nephrotic syndrome were randomly assigned to receive either TAC monotherapy (n = 20) or TAC combined with MMF (n = 20) for 12 months. When patients had been in remission for 1 year on treatment the MMF was stopped and the TAC gradually withdrawn in both groups over 6 months. Patients also received supportive treatment with angiotensin blockade, statins, diuretics and anticoagulation as needed. Primary endpoint was relapse rate following treatment withdrawal. Secondary outcomes were remission rate, time to remission and change in renal function.. 16/20 (80%) of patients in the TAC group achieved remission compared to 19/20 (95%) in the TAC/MMF group (p = 0.34). The median time to remission in the TAC group was 54 weeks compared to 40 weeks in the TAC/MMF group (p = 0.46). There was no difference in the relapse rate between the groups: 8/16 (50%) patients in the TAC group relapsed compared to 8/19 (42%) in the TAC/MMF group (p = 0.7). The addition of MMF to TAC did not adversely affect the safety of the treatment.. Addition of MMF to TAC does not alter the relapse rate of nephrotic syndrome in patients with MN.. This trial is registered with EudraCTN2008-001009-41 . Trial registration date 2008-10-08.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Recurrence; Remission Induction; Tacrolimus; Young Adult

Appropriate immunosuppressive therapy for patients with idiopathic membranous nephropathy (MN) remains controversial. The effect of mycophenolate mofetil (MMF) versus cyclosporine (CsA) combined with low-dose corticosteroids was evaluated in patients with idiopathic MN in a multi-center randomized trial (www.ClinicalTrials.gov NCT01282073).. A total of 39 biopsy-proven idiopathic MN patients with severe proteinuria were randomly assigned to receive MMF combined with low-dose corticosteroids (MMF group) versus CsA combined with low-dose corticosteroids (CsA group), respectively, and followed up for 48 weeks. Complete or partial remission rate of proteinuria and estimated glomerular filtration rate (eGFR) at 48 weeks were compared.. The level of proteinuria at baseline and at 48 weeks was 8.9 ± 5.9 and 2.1 ± 3.1 g/day, respectively, in the MMF group compared to 8.4 ± 3.5 and 3.2 ± 5.7 g/day, respectively, in the CsA group. In total, 76.1% of the MMF group and 66.7% of the CsA group achieved remission at 48 weeks (95% confidence interval, -0.18 to 0.38). There was no difference in eGFR between the two groups. Anti-phospholipase A2 receptor Ab levels at baseline decreased at 48 weeks in the complete or partial remission group (P = 0.001), but were unchanged in the no-response group. There were no significant differences between the two groups in changes in the Gastrointestinal Symptom Rating Scale and Gastrointestinal Quality of Life Index scores from baseline to 48 weeks.. In combination with low-dose corticosteroids, the effect of MMF may not be inferior to that of CsA in patients with idiopathic MN, with similar adverse effects including gastrointestinal symptoms. Trial registry at ClinicalTrials.gov (NCT01282073).

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibiotics, Antineoplastic; Antibodies; Cyclosporine; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Proteinuria; Quality of Life; Receptors, Phospholipase A2; Remission Induction; Treatment Outcome

Immunosuppressive therapy plays an important role in patients with high-risk idiopathic membranous nephropathy (IMN), but the therapeutic modality is still controversial.. Corticosteroid combined with oral tacrolimus (TAC, target trough blood concentration of 4-8 ng/mL), intravenous cyclophosphamide (CYC, 750 mg/m(2)/mo, or oral mycophenolate mofetil (MMF, 1.5-2.0 g/d) were randomly administered for 9 months to 90 patients with IMN proved with renal biopsy with severe proteinuria (>8 g/d).. Eighty-six of the 90 patients completed the study. The total remission (TR) rates in the TAC group were significantly higher than those in the CYC group at 1 and 2 months (p < 0.01) and the MMF group at 1-4 months (p < 0.01). The TR rates were 83.3%, 73.3%, and 70.0% in the TAC, CYC, and MMF groups at 9 months (p = 0.457), and there were no significant differences between the three groups from 5 to 9 months. Furthermore, TAC reduced proteinuria and ameliorated hypoalbuminemia more quickly and effectively than CYC and MMF. We observed no severe adverse events in the three groups.. Tacrolimus combined with corticosteroid had tolerable adverse effects and induced the remission of IMN more effectively and more rapidly. This is the first prospective randomized cohort study to compare three different therapies in patients at high risk for IMN. It provides strong evidence for choosing optimal treatment for patients with IMN. The long-term efficacy of this treatment strategy should be investigated further in future studies.

Topics: Adrenal Cortex Hormones; Adult; China; Cyclophosphamide; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prospective Studies; Proteinuria; Remission Induction; Tacrolimus; Treatment Outcome

Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19-16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08-5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010-1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.

Topics: Adolescent; Adult; Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Hispanic or Latino; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Mycophenolic Acid; Prednisone; Remission Induction; Retrospective Studies; Treatment Outcome; Young Adult

The natural course of idiopathic membranous nephropathy (IMN) is variable and the role of immunosuppressive therapy is controversial. In our centre, the strategy has been conservative: the immunomodulating treatment (glucocorticoids and/or cyclosporine A) has been targeted to patients at high risk of developing progressive renal disease and the cytotoxic drugs have been used cautiously. The aim of this retrospective observational study was to evaluate the efficacy of this strategy.. We evaluated the clinical course and outcome of IMN patients diagnosed between 1993 and 2003. Risk assessment was done during an observation period of ≥6 months after the initial renal biopsy. Patients were followed up until death, the development of end-stage renal disease (ESRD) or the last clinical visit (before December 2006). Treatments and their side effects were recorded.. One hundred and forty-two patients with membranous nephropathy were diagnosed of which 81 were idiopathic. The clinical course of 76 IMN patients (38 high risk and 38 low risk) were followed up [mean duration 66 ± 40 (median 59) months]. Thirty-five patients were treated with immunosuppressive drugs, and at last follow-up, 71% of them were in complete or partial remission. The overall response rate of this therapy was 83%. 11% of the high-risk patients had reached ESRD. For the high-risk patients, 10-year survival (alive with glomerular filtration rate >10 mL/min/1.73 m(2)) was 79%. No major side effects were observed.. This study suggests that targeted, stepwise, cytotoxic drug-sparing immunosuppressive treatment in IMN was associated with favourable renal, as well as overall survival among patient at risk of developing ESRD.

Topics: Cyclophosphamide; Cyclosporine; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Function Tests; Male; Middle Aged; Mycophenolic Acid; Remission Induction; Retrospective Studies; Survival Rate; Treatment Outcome

Calcineurin inhibitors (CNIs) induce remission of proteinuria in most nephrotic patients with membranous glomerulonephropathy (MGN). However, 60% of patients become treatment dependent and are at risk of chronic nephrotoxicity. The aim of this study was to evaluate the efficacy of rituximab in patients with long-term dependence on CNIs.. Thirteen patients with MGN, normal renal function, and proven dependence on CNIs, despite previous treatment with other immunosuppressant drugs, received a single trial of four weekly doses of rituximab (375 mg/m(2)). Outcome measures were the percentage of patients with CNI withdrawal and no evidence of relapse and the percentage of patients with complete or partial remission 30 mo after CNI withdrawal.. After rituximab, proteinuria decreased significantly (2.5 +/- 0,76 basal versus 0.85 +/- 0.17 at 6 mo; P = .0003). CNIs and other immunosuppressant drugs could be withdrawn in all patients with no evidence of relapse. After CNI withdrawal, GFR increased significantly (90.3 +/- 15 basal to 106.4 +/- 20 at 3 mo with a mean increase of 15.3% [range 0-20]). Three patients suffered a relapse of nephrotic proteinuria 19, 23, and 28 mo after rituximab treatment; all were successfully treated with a second course of rituximab. At 30 mo, all patients were in remission.. In patients with MGN with long-term CNI dependence, rituximab can be an effective tool to overcome dependence on CNI, thus avoiding the risk of nephrotoxicity related to the chronic exposure to these drugs.

Topics: Adult; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Biopsy; Calcineurin Inhibitors; Enzyme Inhibitors; Female; Follow-Up Studies; Glomerulonephritis, Membranous; Humans; Immunologic Factors; Kidney; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Proteinuria; Remission Induction; Rituximab; Substance Withdrawal Syndrome

Treatment of patients with membranous glomerulonephritis (MGN) is controversial because of the lack of clear benefit of the immunosuppressive regimens on patient or renal survival. The objective of this study is to evaluate the efficacy and safety of mycophenolate mofetil (MMF) for patients with MGN.. 1-year prospective, randomized, and controlled clinical trial.. 36 patients with biopsy-proven idiopathic MGN and nephrotic syndrome.. 19 patients received MMF (2 g/d) for 12 months and 17 patients were in the control group. All patients had the same conservative treatment based on renin-angiotensin blockers, statins, low-salt and low-protein diet, and diuretics in case of edema.. End points were the mean proteinuria over creatinuria ratio in mg/g throughout the study and numbers of complete and partial remissions at 1 year (month 12). Data were analyzed on an intention-to-treat analysis.. Mean proteinuria over creatinuria ratio was stable in both groups throughout the study (P = 0.1). Mean proteinuria over creatinuria ratio was 4,690 +/- 2,212 mg/g in the MMF group and 6,548 +/- 4,601 mg/g in the control group (95% confidence interval of the difference, -619 to +4,247; P = 0.1). Remission was complete in 3 patients (1 in the MMF group, 2 in the control group; P = 0.5) and partial in 11 patients (6 in the MMF group, 5 in the control group; P = 0.9). The probability of complete or partial remission did not differ between the 2 groups after 12 months (relative risk, 0.92; 95% confidence interval, 0.48 to 1.75; P = 0.7). Kidney function was stable in the 2 groups according to estimated glomerular filtration rate and serum creatinine level.. The small number of patients and short follow-up prevent generalizations.. A 12-month regimen of MMF did not decrease mean proteinuria over creatinuria ratio or increase partial and complete remissions. Serious adverse effects were observed in 4 patients (20%) receiving MMF.

Topics: Adult; Aged; Creatinine; Dose-Response Relationship, Drug; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Outcome Assessment, Health Care; Prospective Studies; Proteinuria; Treatment Outcome

The current treatment regimes for patients with nephrotic syndrome due to idiopathic membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) are based on steroids and/or cytotoxic agents. Data on the effect of mycophenolate mofetil (MMF) for these conditions are scarce and confounding.. We compared the efficacy of an MMF-based therapy with standard therapies in inducing remission in adult nephrotics with MN and FSGS in a randomized pilot study. MMF was given at 2 g/day for 6 months along with prednisolone at 0.5 mg/kg/day for 2-3 months. Conventional therapy was prednisolone 1 mg/kg/day for 3-6 months for FSGS and alternating monthly cycles of steroids and cyclophosphamide for 6 months for MN. The primary end point was change in urinary protein/creatinine ratio.. A total of 54 patients (21 MN and 33 FSGS) were recruited; 28 were randomized to receive MMF (group A) and 26 were on conventional treatment (group B). There was no difference in the proportion of patients achieving remission in two groups (64 and 80% in MN and 70 and 69% in FSGS). The frequency of relapses and incidence of infections was also similar. FSGS patients in group A achieved remission faster and received a lower cumulative steroid dose.. A 6-month treatment with MMF is as effective as the conventional treatment for primary treatment of MN and FSGS in the short term. It induces remission faster and reduces steroid exposure in FSGS patients. Studies with more cases and longer follow-up are required to evaluate its impact on preservation of kidney function.

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cyclophosphamide; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Kidney Function Tests; Male; Mycophenolic Acid; Pilot Projects; Prednisolone; Probability; Risk Assessment; Severity of Illness Index; Statistics, Nonparametric; Treatment Outcome

Membranous nephropathy is a common cause of nephrotic syndrome (NS) in adults. Its treatment is still under debate.. We report our experience in a pilot study using initially low doses of steroids and tacrolimus (Tac). After 3 months of treatment, mycophenolate mofetil (MMF) was added if the proteinuria was higher than 1 g/day.. In accordance with this standard, 21 patients entered the study. A proteinuria level lower than 1 g/day was reached at month 3 of therapy with steroids and Tac in 11 patients. These patients continued this treatment for 12 months. MMF was added in nine cases after the third month and triple therapy was maintained for 12 more months. Two patients were withdrawn because of side effects. At the end of the treatment, remission of the NS was present in 15 out of all the patients (71.4%). Remission of the NS was complete in eight (53.3%) patients and partial in seven (46.7%) others. The remaining four patients did not respond. There were no significant changes in renal function. At a mean time of 23.1 months after treatment was discontinued, 11 (73.3%) patients had relapsed.. In this trial, treatment with tacrolimus showed a good efficacy but a high relapse rate when it was discontinued.

Topics: Adrenal Cortex Hormones; Adult; Aged; Albuminuria; Biopsy; Cholesterol; Creatinine; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Mycophenolic Acid; Proteinuria; Tacrolimus

Cyclophosphamide can decrease proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a high risk of side effects. We studied whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effects.. Clinical trial with historic controls.. 32 cases and 32 controls with idiopathic membranous nephropathy and renal insufficiency at multiple centers. For comparison, we selected matched historic controls treated with cyclophosphamide.. MMF, 1 g twice daily, for 12 months versus cyclophosphamide, 1.5 mg/kg/d, for 12 months. Both groups also received intermittent methylprednisolone and alternate-day prednisone.. Serum creatinine, proteinuria, and side effects during and after treatment.. Median follow-up was 23 months (range, 11 to 46 months). Median serum creatinine levels were 1.8 mg/dL (159 micromol/L) in both groups at baseline and 1.4 mg/dL (124 micromol/L) in the MMF group versus 1.3 mg/dL (115 micromol/L) in the cyclophosphamide group at 12 months (P = 0.4). Proteinuria values at baseline and 12 months were protein of 8.40 and 1.41 g/d in the MMF group versus 9.19 and 1.13 g/d in the cyclophosphamide group (P = 0.5 at 12 months), respectively. Cumulative incidences of remission of proteinuria at 12 months were 66% in the MMF group versus 72% in the cyclophosphamide group (P = 0.3). Five patients (16%) in the MMF group versus none in the cyclophosphamide group had disease that did not respond to therapy (P = 0.05). Twelve patients (38%) experienced a relapse and 9 patients (31%) were re-treated in the MMF group compared with 4 (13%) and 2 patients (6%) in the cyclophosphamide group (P < 0.01 and P = 0.024, respectively). Side effects occurred in 24 patients (75%) in the MMF group and 22 patients (69%) in the cyclophosphamide group (P = 0.6).. Nonrandomized control group, short duration of follow-up.. A 12-month course of MMF decreased proteinuria and improved renal function in the majority of patients, but did not appear as effective or better tolerated than cyclophosphamide. Long-term data and randomized controlled trials are needed to ascertain the efficacy of MMF in patients with idiopathic membranous nephropathy.

Topics: Adult; Aged; Cohort Studies; Cyclophosphamide; Female; Follow-Up Studies; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Mycophenolic Acid; Proteinuria

Retrospective and anecdotal data suggest that mycophenolate mofetil (MMF) might be effective when given as rescue therapy for membranous nephropathy (MN). Prospective controlled data on MMF and prednisolone as primary therapy are lacking.. A prospective, randomized, controlled, open-label study was performed to investigate the efficacy and tolerability of MMF and prednisolone as primary treatment in MN with nephrotic syndrome. MMF and prednisolone given for 6 months was compared against a modified Ponticelli regimen in 20 patients, with follow up of 15 months.. MMF with prednisolone and the comparative immunosuppressive regimen showed similar efficacy in proteinuria reduction, despite a lower cumulative prednisolone dose in the MMF group (3.80 +/- 0.28 vs 9.93 +/- 0.25 g, P < 0.001). Remission (composite of 'complete' and 'partial') rates were 63.6% and 66.7% in the MMF group and control group, respectively (P = 1.000). Serum creatinine and creatinine clearance remained stable during follow up. Cumulative relapse rate was 23.1% at 2 years. Chlorambucil resulted in more leucopenia compared with MMF.. Data from this pilot study indicate that more than 60% of patients with MN and nephrotic syndrome respond to combined MMF and prednisolone treatment, and suggest potential benefits of MMF as being steroid-sparing and having less adverse effects compared with other commonly used cytotoxic agents.

Topics: Adolescent; Adult; Aged; Female; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Treatment Outcome

Treatment of primary glomerular diseases may be unsuccessful or have potential toxicities. Therefore, we evaluated the use of mycophenolate mofetil (MMF) for empirical treatment of primary glomerulopathies.. Forty-six patients with biopsy-proven primary glomerulopathies received MMF for > or =3 months as adjunctive or primary treatment. Median (range) 24-hour urine protein to creatinine ratio (Up/c) and serum creatinine at the start and end of MMF therapy were compared using the Wilcoxon signed-ranks test.. Overall, the median Up/c decreased from 4.7 (range <0.1, 20.3) to 1.1 (<0.1, 14.3; P < 0.001) at the end of MMF treatment with no significant change in median serum creatinine 1.3 (0.6 to 6.1) to 1.2 (0.5 to 6.5) mg/dL. Median serum albumin increased from 3.4 (1.4, 4.6) to 4.1 (1.7, 48) g/dL (P < 0.001) and the median serum cholesterol decreased from 270 (148, 795) to 220 (140, 309) mg/dL (P < 0.001) post-treatment. For those with minimal change disease, a complete steroid withdrawal was accomplished in 5/6 steroid dependent patients. Focal segmental glomerulosclerosis (FSGS) patients had a median Up/c that decreased from 2.7 (0.1, 20.3) to 0.8 (<0.1, 8.2; P = 0.001) in 18 patients. In membranous nephropathy (MN) patients, the median Up/c decreased from 7.3 (0.1, 18.5) to 1.5 (<0.1, 14.3) (P = 0.001) in 17 patients. No significant change in median serum creatinine was detected in FSGS or MN patient groups during treatment.. Empirical MMF therapy in the majority of patients with primary glomerulopathies was well tolerated and achieved the goals of steroid withdrawal, improvement of nephrotic syndrome, and stabilization of renal function.

Topics: Adolescent; Adult; Aged; Creatinine; Female; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Kidney Diseases; Kidney Glomerulus; Male; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Proteinuria; Steroids

Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Optimal therapy for this disease is still debated. We report our experience using mycophenolate mofetil (MMF), an immunosuppressive agent widely used in transplant recipients, to treat 16 nephrotic patients with MN. All patients had biopsy-documented MN; secondary forms were ruled out. Fifteen patients had steroid-resistant disease; cytotoxic agents had failed in 6 patients and cyclosporine therapy had failed in 5 patients. Patients were treated with MMF (dose range, 500 to 2,000 mg) for a mean of 8 months. Six patients experienced a halving of proteinuria, which occurred after a mean duration of 6 months of therapy. Partial remissions occurred in 2 patients. There were no significant changes in mean values for serum creatinine, serum albumin, or proteinuria. Mean cholesterol levels were significantly less. Side effects of MMF were infrequent and generally mild. In summary, MMF appears to reduce proteinuria in some patients with idiopathic MN previously resistant to steroids, cytotoxic agents, or cyclosporine. Further trials with this agent are warranted.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cholesterol; Creatinine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Proteinuria

Late-onset neutropenia (LON) is an underrecognized complication of rituximab treatment. We undertook this study to describe its incidence, risk factors, clinical features, management, and recurrence.. We conducted a single-center retrospective cohort study of 738 adult patients with autoimmune disease who were treated with rituximab to induce continuous B cell depletion. The primary outcome measure was LON, defined as an unexplained absolute neutrophil count of <1,000 cells/µl during B cell depletion. Secondary outcome measures included incidental diagnosis, fever, sepsis, filgrastim use, and recurrent LON. We assessed predictors of LON using Cox proportional hazards regression models. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated.. We identified 107 episodes of LON in 71 patients. The cumulative incidence at 1 year of B cell depletion therapy was 6.6% (95% CI 5.0-8.7). The incidence rate during the first year was higher compared to thereafter (7.2 cases per 100 person-years [95% CI 5.4-9.6] versus 1.5 cases per 100 person-years [95% CI 1.0-2.3]). Systemic lupus erythematosus and combination therapy with cyclophosphamide were each independently associated with an increased risk of LON (adjusted HR 2.96 [95% CI 1.10-8.01] and 1.98 [95% CI 1.06-3.71], respectively). LON was not observed in minimal change disease or focal segmental glomerulosclerosis. The majority of episodes (59.4%) were asymptomatic. Fever and sepsis complicated 31.3% and 8.5% of episodes, respectively. Most patients (69%) were treated with filgrastim. Rituximab rechallenge occurred in 87% of patients, of whom 21% developed recurrent LON.. LON is common and often incidental. Most cases are reversible and respond well to filgrastim. However, LON can be associated with serious infections and thus warrants vigilant monitoring.

Topics: Adult; Aged; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Asymptomatic Diseases; Autoimmune Diseases; Azathioprine; Cyclophosphamide; Drug Therapy, Combination; Female; Fever; Filgrastim; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematologic Agents; Humans; Immunologic Factors; Incidence; Lupus Erythematosus, Systemic; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Neutropenia; Proportional Hazards Models; Recurrence; Retrospective Studies; Risk Factors; Rituximab; Sepsis

Studies on repeat renal biopsies in membranous LN (MLN) are limited, and evaluation of treatment response is mainly based on proteinuria. EM of renal biopsies from rituximab (RTX)-treated MLN patients has revealed resorption of sub-epithelial ICs. Whether resorption phenomena are useful for treatment evaluation, or differs between treatment regimens is not known. We studied EM findings and clinical treatment response in MLN patients after RTX vs conventional immunosuppressive treatment.. Twenty-four patients with MLN and renal biopsies performed before and after treatment were included in this retrospective observational study. Laboratory data were collected at both biopsy occasions. Seven patients had received RTX and 17 had received conventional treatment (CYC, MMF or AZA). Electron micrographs of renal tissue were scored using an arbitrary scale (0-3) for the level of sub-epithelial ICs, resorption of ICs and podocyte fusion.. Sub-epithelial ICs decreased after treatment, however not significantly and with no difference between treatments. The resorption phenomena increased after RTX (P = 0.028), but not after conventional therapy (P = 0.29). Six out of seven (86%) RTX-treated patients had increased resorption vs 7/17 (41%) after conventional therapies (P = 0.047). Clinical responders had more pronounced resorption of ICs vs non-responders (P = 0.022).. We report increased resorption of ICs in repeat renal biopsies in MLN, especially after RTX treatment. Increased resorption phenomena were associated with clinical response, suggesting that EM findings may be useful for treatment evaluation in MLN. Although of limited size, the study indicates that RTX is effective both clinically and at a tissue level.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antigen-Antibody Complex; Azathioprine; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Microscopy, Electron; Middle Aged; Mycophenolic Acid; Podocytes; Rituximab; Treatment Outcome; Young Adult

Lupus nephritis requires antinuclear antibodies as classification criteria. There is a group of patients with nephrotic syndrome and conclusive histopathological findings for lupus nephritis, without classification criteria for systemic lupus erythematosus (SLE) or extrarenal manifestations. These groups of patients have been described as "lupus-like" nephritis or "renal-limited lupus nephritis".. Renal biopsy with histopathological evaluation with "full-house" immune-reactants in patients with negative antinuclear antibodies.. We report four cases with nephrotic syndrome and one with hematuria-proteinuria syndrome: two with impaired glomerular filtration rate and three with preserved renal function; urinary sediment with hematuria without dysmorphia and without extrarenal manifestations for autoimmune disease, negative antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA); normal C3 and C4 complement levels. Renal biopsy in all cases was consistent for lupus nephritis class V. All patients received treatment as lupus nephritis protocol; only one case received induction with cyclophosphamide and methylprednisolone boluses, the rest received mycophenolic acid and prednisone as induction and maintenance. Two of the cases induced with mycophenolic acid relapsed, requiring cyclophosphamide for 6 months, achieving complete remission. All patients received renin-angiotensin-aldosterone system blockade and hydroxychloroquine. At follow-up, 4 cases still have negative antibodies and are without extrarenal manifestations for SLE classification criteria. The other case, during pregnancy several years after initial diagnosis, had preeclampsia with nephrotic proteinuria and a new determination of positive ANA and anti-dsDNA antibodies, complement levels below normal limits.. The follow-up of patients with membranous glomerulopathy must be close; lupus like nephritis may be the first manifestation of the disease.

Topics: Antibodies, Antinuclear; Complement System Proteins; Cyclophosphamide; Female; Glomerulonephritis, Membranous; Hematuria; Hospitals; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Mexico; Mycophenolic Acid; Pregnancy; Proteinuria

A 34-year-old female patient presented to our hospital with lower extremity edema and proteinuria during pregnancy. Renal biopsy was performed and the patient was diagnosed with nephrotic syndrome due to lupus-like membranous nephropathy. This diagnosis was reached upon as laboratory findings upon admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed negative, did not fulfill the criteria for systemic lupus erythematosus (SLE) proposed by the American College of Rheumatology (ACR) and the patient did not reveal any typical physical manifestations of SLE. Methylprednisolone pulse therapy was started followed by oral administration of prednisolone. Urinary protein excretion diminished after 1 year of treatment. Eleven years later, the same patient was admitted to our hospital again with relapse of nephrotic syndrome. Laboratory findings upon second admission, wherein both anti-nuclear and anti-double-stranded DNA antibodies revealed positive, fulfilled the ACR criteria. Renal biopsy was performed again, resulting in a diagnosis of lupus nephritis. Steroid therapy combined with administration of mycophenolate mofetil led to an incomplete remission. Immunofluorescence studies confirmed the presence of IgG, IgM, C3, and C1q in renal biopsy specimens both at first and second admissions. Furthermore, immunofluorescence studies confirmed the presence of IgG1-4 in the first biopsy and tubuloreticular inclusions (TRIs) were revealed using electron microscopy. The present case represents the possibility that characteristic pathological findings of lupus nephritis, including TRIs, can reveal themselves before a diagnosis of SLE.

Topics: Adult; Antibodies, Antinuclear; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glomerulonephritis, Membranous; Glucocorticoids; Hospitalization; Humans; Immunoglobulin G; Kidney; Lupus Erythematosus, Systemic; Lupus Nephritis; Methylprednisolone; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Recurrence; Remission Induction

To date, a recognized treatment for refractory membranous nephropathy (MN) has not been established. Recently, several reports have indicated the efficacy of rituximab as a novel treatment option. However, only a few published accounts exist of rituximab therapy for idiopathic MN (IMN) in the Asian population. We present the cases of three IMN patients who were treated with single-dose rituximab after they showed no response to conventional therapies, including corticosteroids, cyclosporine, cyclophosphamide, mizoribine, and mycophenolate mofetil. Although one case showed no response, a complete or incomplete remission was achieved in the other two cases. Rituximab may therefore be a beneficial treatment option for IMN.

Topics: Adrenal Cortex Hormones; Adult; Aged; Asian People; Cyclophosphamide; Cyclosporine; Glomerulonephritis, Membranous; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Ribonucleosides; Rituximab

Kimura disease (KD) is a rare inflammatory soft tissue disorder of unknown origin most frequent in Asians, the prevalence of which is growing in Western countries. Painless papules and/or nodules with a predilection for the head and the neck region, lymphadenopathies, parotid gland involvement, eosinophilia, and raised IgE levels are parts of its presentation. Renal involvement with various forms of glomerulonephritis, including membranous nephropathy (MN), can occur and is generally associated with a proteinuria that encompasses nephrotic syndrome. Corticosteroids are the mainstay of treatment of KD-associated glomerulonephritis, but steroids withdrawal is often followed by relapsing nephrotic syndrome. Various immunosuppressive agents have been tested to prolong the remission of KD-associated nephrotic syndrome while tapering steroids, but they are only partly effective or associated with significant complications. To the best of our knowledge, we describe here the first case of KD-related membranous glomerulonephritis with a favorable evolution and a sustained remission of 4 years under prolonged therapy with mycophenolic acid (MPA). MPA and its active metabolite, mycophenolate mofetil (MMF), treatments as supportive therapies to corticosteroids and ACE inhibitors should be further investigated in KD-related membranous nephropathies.
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Topics: Angiolymphoid Hyperplasia with Eosinophilia; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Treatment Outcome

Kimura's disease (KD) with renal involvement is a rare disease. Optimal treatments are still not well established. It is necessary to analyze clinicopathological features, treatment responses, and prognosis for improving KD diagnosis and treatment.. Clinicopathological data, treatment responses, and prognosis were collected and analyzed retrospectively.. The patients consisted of 27 males and 2 females, with an average age of 35.5 ± 15.1 (13 - 61) years. 27 exhibited proteinuria ranging from 0.730 to 14.1 g/24 h (5.98 ± 3.40 g/24 h). Hypertension, renal insufficiency (serum creatinine (Scr) > 1.24 mg/dL), and microhematuria occurred in 4 (13.8%), 11 (37.9%), and 13 (44.8%) cases, respectively. Light microscopy (LM) identified mesangium proliferation, minimal change, focal and segmental glomerulosclerosis (FSGS), membranous glomerulonephritis, membranoproliferative glomerulonephritis (MPGN), and acute tubular necrosis in 14, 8, 3, 2, 1, and 1 cases, respectively. All were treated with Tripterygium wilfordii (TW), prednisone, leflunomide (LEF), tacrolimus (FK506), myophenolate mofetil (MMF), or renin-angiotensin system blockers (RASI). 26 patients were followed up for 1.60 - 108.7 months (39.6 ± 28.7). After treatments, urinary red blood cells (RBC) decreased in all. The amount of 24-hour urinary protein (24-hUPE) decreased in 24 patients. 22 reached complete remission (CR), 4 partial remissions (PR). The patients who did not relapse were younger than those who relapsed.. KD with renal involvement occurs predominantly among 35 - 50 year old Chinese patients with male predilection. The most common features are proteinuria, hypertension, micro hematuria with minimal change, and mesangial proliferative glomerulonephritis. Most were responsive to treatment, but could relapse. Gender, age, and hypertension are associated with KD recurrence. The prognosis is good mostly.

Topics: Adolescent; Adult; Angiolymphoid Hyperplasia with Eosinophilia; Anti-Inflammatory Agents; China; Female; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Hematuria; Humans; Hypertension; Immunosuppressive Agents; Isoxazoles; Leflunomide; Male; Middle Aged; Mycophenolic Acid; Phytotherapy; Plant Preparations; Prednisone; Prognosis; Proteinuria; Recurrence; Renal Insufficiency; Retrospective Studies; Tacrolimus; Tripterygium; Young Adult

There are very little data available regarding nephrotic syndrome (NS) in elderly (aged ≥65 years) Japanese. The aim of this study was to examine the causes and outcomes of NS in elderly patients who underwent renal biopsies between 2007 and 2010.. From July 2007 to June 2010, all of the elderly (aged ≥65 years) Japanese primary NS patients who underwent native renal biopsies and were registered in the Japan renal biopsy registry (J-RBR; 438 patients including 226 males and 212 females) were identified. From this cohort, 61 patients [28 males and 33 females including 29, 19, 6, 4, and 3 patients with membranous nephropathy (MN), minimal change nephrotic syndrome (MCNS), focal segmental glomerulosclerosis (FSGS), membranoproliferative glomerulonephritis (MPGN), and other conditions, respectively] were registered from the representative multi-centers over all districts of Japan, and analyzed retrospectively. The treatment outcome was assessed using proteinuria-based criteria; i.e., complete remission (CR) was defined as urinary protein level of <0.3 g/day or g/g Cr, and incomplete remission type I (ICR-I) was defined as urinary protein level of <1.0-0.3 g/day or g/g Cr, and renal dysfunction was defined as a serum creatinine (Cr) level of 1.5 times the baseline level.. In this elderly primary NS cohort, MN was the most common histological type of NS (54.8 %), followed by MCNS (19.4 %), FSGS (17.4 %), and MPGN (8.4 %). Of the patients with MN, MCNS, or FSGS, immunosuppressive therapy involving oral prednisolone was performed in 25 MN patients (86.2 %), 18 MCNS patients (94.7 %), and all 6 FSGS patients (100 %). CR was achieved in all 19 (100 %) MCNS patients. In addition, CR and ICR-I were achieved in 16 (55.2 %) and 18 (62.1 %) MN patients and 4 (66.7 %) and 5 (83.3 %) FSGS patients, respectively. There were significant differences in the median time to CR among the MCNS, FSGS, and MN patients (median: 26 vs. 271 vs. 461 days, respectively, p < 0.001), and between the elderly (65-74 years, n = 7) and very elderly (aged ≥75 years, n = 12) MCNS patients (7 vs. 22 days, p = 0.037). Relapse occurred in two (6.9 %) of the MN and nine (47.4 %) of the MCNS patients. Renal dysfunction was observed in five (7.2 %) of the MN patients. Serious complications developed in eight (14.8 %) patients, i.e., two (3.7 %) patients died, four (7.4 %, including three MCNS patients) were hospitalized due to infectious disease, and two (3.7 %) developed malignancies. The initiation of diabetic therapy was necessary in 14 of the 61 patients (23.0 %) with much higher initial steroid dosage.. Renal biopsy is a valuable diagnostic tool for elderly Japanese NS patients. In this study, most of elderly primary NS patients respond to immunosuppressive therapy with favorable clinical outcomes. On the other hand, infectious disease is a harmful complication among elderly NS patients, especially those with MCNS. In future, modified clinical guidelines for elderly NS patients should be developed.

Topics: Aged; Aged, 80 and over; Biopsy; Creatinine; Cyclophosphamide; Cyclosporine; Female; Follow-Up Studies; Glomerulonephritis; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Japan; Kidney; Male; Methylprednisolone; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisolone; Proteinuria; Recurrence; Registries; Retrospective Studies; Ribonucleosides; Treatment Outcome

The optimal timing and duration of immunosuppressive therapy for idiopathic membranous nephropathy (iMN) have been debated. This study aimed to evaluate whether measuring the antibody against the phospholipase A2 receptor (PLA2R-ab) at start and end of therapy predicts long-term outcome and therefore may inform this debate.. This observational study included all consecutive high-risk patients with progressive iMN observed from 1997 to 2005 and treated with oral cyclophosphamide (CP) or mycophenolate mofetil (MMF) in combination with corticosteroids for 12 months. Patients were prospectively followed, and outcome was ascertained up to 5 years after completion of immunosuppressive therapy. Serum samples were collected before and after completion of therapy. PLA2R antibodies were determined retrospectively in stored samples using ELISA.. In total, 48 patients (37 men) were included. The median age was 55 years (range, 34-75), and the median serum creatinine level was 1.60 mg/dl (range, 0.98-3.37 mg/dl). Twenty-two patients received MMF and 26 received CP. At baseline, PLA2R-abs were present in 34 patients (71%). Baseline characteristics and outcome did not significantly differ between patients negative or positive for PLA2R-ab. In PLA2R-ab-positive patients, treatment resulted in a rapid decrease of antibodies: median anti-PLA2R-ab, 428 U/ml (range, 41-16,260 U/ml) at baseline and 24 U/ml (range, 0-505 U/ml) after 2 months. The PLA2R-ab levels at baseline did not predict initial response, but antibody status at end of therapy predicted long-term outcome: After 5 years, 14 of 24 (58%) antibody-negative patients were in persistent remission compared with 0 of 9 (0%) antibody-positive patients (P=0.003).. These data suggest that in PLA2R-ab-positive patients, measuring PLA2R-abs at the end of therapy predicts the subsequent course.

Topics: Adult; Aged; Autoantibodies; Biomarkers; Cyclophosphamide; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Male; Middle Aged; Mycophenolic Acid; Predictive Value of Tests; Receptors, Phospholipase A2; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Autoantibodies; Cyclophosphamide; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Receptors, Phospholipase A2

Idiopathic membranous nephropathy (IMN) is a rare form of childhood nephropathy. To date there are no standardized protocols of management for this condition in children. The aim of this study is to report on 4 children with IMN who were treated with mycophenolate mofetil (MMF).. MMF was given in combination with low dose steroids and angiotensin converting enzyme antagonists in a dose of 1,200 mg/m2 body surface area in two divided doses for a minimum of 6 months.. All children had histopathological findings in keeping with Stage III membranous nephropathy. At the last hospital visit, 3 children had achieved a > 50% reduction of proteinuria with preservation of renal function. One patient who failed to respond progressed to Stage III chronic kidney disease. None of the children who were treated with MMF experienced any major side effects of the drug.. MMF, administered over a limited period, served as a safe and effective immunosuppressive agent in the treatment of this condition, in conjunction with low dose steroids and angiotensin converting enzyme inhibitors. Large multicenter randomized studies of children with IMN are necessary to assess the efficacy and long term safety of MMF.

Topics: Adrenal Cortex Hormones; Angiotensin-Converting Enzyme Inhibitors; Child; Child, Preschool; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid

Fibrillary glomerulonephritis (FGN) is a morphologically defined entity characterized by glomerular accumulations of non-branching, randomly arranged fibrils; these differ from amyloid fibrils by their larger size and lack of reactivity with Congo red and other amyloid-specific dyes. FGN is a rare disease and may mimic membranous nephropathy under routine light microscopy and immunohistochemistry. However, electron microscopy shows the fibrillary nature of these glomerular deposits. We report a rare case of membranous nephropathy complicated by fibrillary deposits in a 60-year-old man with a history of bone tuberculosis.

Topics: Anti-Inflammatory Agents; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Kidney Glomerulus; Male; Middle Aged; Mycophenolic Acid; Prednisone; Renal Dialysis; Tuberculosis, Osteoarticular

Nephrotic syndrome (NS) is a recognized complication of immune tolerance induction (ITI) therapy, a treatment strategy used to treat inhibitors in patients with hemophilia B receiving factor IX concentrate.. We present a 4-year-old boy with hemophilia B and an inhibitor who underwent ITI, and developed NS 19 months into this therapy. A percutaneous renal biopsy was safely performed with factor IX (FIX) concentrate administration both preceding and following the procedure. The patient's inhibitor level had increased to 1.4-1.6 Bethesda Units just prior to the onset of proteinuria. Histology confirmed segmental membranous nephropathy (MGN). The patient was continued on FIX concentrate as ITI and also received 4 weekly doses of rituximab and ongoing immunosuppression with mycophenolate mofetil. This resulted in the complete resolution of his inhibitor and his NS. He continues with a modified ITI regimen and remains inhibitor-free without proteinuria >12 months post-biopsy.. Hemophilia B patients undergoing ITI should be regularly screened for NS. At first detection of proteinuria, with proper precautions, a percutaneous kidney biopsy can be performed safely in patients with low levels of inhibitor. Our patient had segmental MGN with complete remission of NS.

Topics: Antibodies; Antibodies, Monoclonal, Murine-Derived; Biopsy; Child, Preschool; Coagulants; Factor IX; Glomerulonephritis, Membranous; Hemophilia B; Humans; Immune Tolerance; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Rituximab; Time Factors; Treatment Outcome

Topics: Adrenal Cortex Hormones; Adult; Atrophy; Biomarkers, Tumor; Carcinoma, Renal Cell; Glomerulonephritis, Membranous; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Kidney Transplantation; Male; Mucin-1; Mycophenolic Acid; Nephrectomy; Postoperative Complications; Reoperation; Tacrolimus

We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

Topics: Adult; Biopsy; Glomerulonephritis, Membranous; Humans; Kidney; Male; Mycophenolic Acid; Nephrotic Syndrome; Polycystic Kidney, Autosomal Dominant; Proteinuria

We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.

Topics: Drug Administration Schedule; Glomerulonephritis, Membranous; Humans; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome

A 49-year-old woman with a 1-year history of Sjögren's syndrome was diagnosed with cutaneous leukocytoclastic vasculitis and necrotizing crescentic membranous glomerulonephritis. Antineutrophil cytoplasmic antibodies targeting myeloperoxidase were found. She reported a transient episode of nephritis 4 years earlier. This pattern of kidney disease is not typical of Sjögren's syndrome. Methylprednisolone boluses followed by oral glucocorticoid therapy were given in combination with mycophenolate mofetil. Renal function stabilized after 2 months, and tests for anti-myeloperoxidase reverted to negative.

Topics: Administration, Oral; Antibodies, Antineutrophil Cytoplasmic; Drug Therapy, Combination; Female; Glomerulonephritis, Membranous; Glucocorticoids; Humans; Immunosuppressive Agents; Injections, Intravenous; Methylprednisolone; Middle Aged; Mycophenolic Acid; Peroxidase; Sjogren's Syndrome; Treatment Outcome; Vasculitis, Leukocytoclastic, Cutaneous

Studies of immunosuppressive therapy, particularly mycophenolate mofetil (MMF), in membranous lupus nephritis (MLN) are limited. We report on our experience with primary (first-line) MMF therapy to induce and sustain renal remission in MLN with and without a concurrent proliferative lesion. Systemic lupus erythematosus (SLE) patients were studied, retrospectively, if treated with MMF for newly diagnosed MLN. Complete remission was defined as proteinuria less than 0.5 g/24 h, inactive urine sediment and normal estimated glomerular filtration rate. Response in pure MLN (Group I, n=10) was compared with mixed MLN and proliferative lupus nephritis (Group II, n=19). By 12 months, 4 (40%) patients in Group I and 7 (36.8%) in Group II achieved complete remission (P=0.87). One (10%) patient in Group I and 2 (10.5%) in Group II had worsening renal disease (P=0.97). Mean time to remission was more than seven months in both groups. The remaining patients had stable disease without improvement or worsening. Only 2 of 11 achieving initial remission had a relapse with an average of 28 months of follow-up after remission. Self-limited gastrointestinal symptoms occurred in 12 patients, none requiring withdrawal of the drug. Mycophenolate mofetil as a primary therapy in MLN was successful in inducing complete remission in about 40% of MLN, particularly in patients with mild proteinuria. However, 12 months of therapy was necessary for best outcomes. Response rate was not different in the presence or absence of a proliferative lesion.

Topics: Adolescent; Adult; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Mycophenolic Acid; Recurrence; Remission Induction; Retrospective Studies; Time Factors; Treatment Outcome

Idiopathic membranous nephropathy (IMN) is one of the most common causes of primary nephrotic syndrome in adults. However, it is a relatively rare entity in the pediatric population and there is a paucity of data about the incidence, prognosis, and optimal treatment of IMN in children and adolescents. We conducted this study to evaluate pediatric patients with IMN in order to clarify the presentation, response to therapy, and clinical outcome.. A retrospective chart review was performed on patients identified with biopsy-proven IMN between 1988-2005. Patients with systemic lupus erythematosus or hepatitis-related lesions were excluded. The following data were tabulated: age, gender, ethnicity, presenting clinical and laboratory findings, proteinuria in a first morning urine specimen, estimated glomerular filtration rate (GFRe), histopathology, type and duration of treatment, and clinical status at final evaluation.. 13 cases of IMN were identified out of 460 renal biopsies performed for evaluation of primary kidney disease during the study interval. Mean age was 9.6 +/- 4.6, gender 6 M:7 F, ethnicity 8 W:2 B:3 H. At the initial visit hematuria was present in 9 patients, edema in 5, nephrotic-range proteinuria in 5, and hypertension in 3. Mean urinary protein:creatinine ratio 3.3 +/- 2.5 and all patients had a normal GFRe. Classic glomerular findings of IMN were seen in all renal specimens, with concomitant interstitial changes in 2 cases. Treatment included an angiotensin converting enzyme inhibitor or angiotensin receptor blocker in 11 cases. Most patients were also given immunosuppressive medications - prednisone in 10, a calcineurin inhibitor in 5, and mycophenolate mofetil or azathioprine in 3 patients. At the last follow-up, 42 +/- 35 months after the diagnostic biopsy, 7 children were hypertensive and the urine protein:creatinine ratio was 2.3 +/- 3.1. The mean GFRe was 127 +/- 57 mL/min/m2. Three patients had Chronic Kidney Disease Stage 3, all of whom were also hypertensive.. IMN is a rare but serious glomerulopathy in pediatrics. We estimate that it accounts for approximately 3% of renal biopsies. Long-term prognosis is guarded because approximately 50% of patients may have evidence of progressive kidney disease.

Topics: Adolescent; Biopsy; Child; Child, Preschool; Female; Glomerular Filtration Rate; Glomerulonephritis, Membranous; Humans; Hypertension; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Male; Mycophenolic Acid; Prednisone; Prognosis; Proteinuria; Retrospective Studies; Time Factors; Treatment Outcome

Topics: Adult; Glomerulonephritis, Membranoproliferative; Glomerulonephritis, Membranous; Hepatitis B; Hepatitis B virus; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Virus Activation

Lupus membranous nephropathy (LMN) presents a difficult clinical problem as no particular treatment has been proven to be effective. Studies have shown good results with mycophenolate mofetil (MMF) in proliferative lupus nephropathy (LN) (WHO class III and IV disease).. To study whether MMF treatment was effective in membranous predominant LN in patients resistant to or intolerant of other immunosuppressive agents.. We retrospectively studied 10 patients with systemic lupus erythematosus who had biopsy-proven predominant LMN (six Vc patients and four Va or Vb patients). Previous treatments included cyclophosphamide, azathioprine, ciclosporin and corticosteroids. The following parameters were recorded at baseline and follow-up: blood pressure, ECLAM, proteinuria, serum albumin and creatinine, routine haematology and immunology.. The study included eight women and two men, mean age 38.4 +/- 7.1 yr (range 30-49 yr). The racial distribution was as follows: five Caucasian, and five Black patients. The mean treatment time with MMF was 18.8 +/- 15.4 months (range 3-52 months). Twenty-four-hour urinary protein excretion was reduced from median 2.26 g (range 0-7.92 g) to median 0.66 g (range 0.08-3.85 g) at follow-up (P = 0.0039). Serum albumin increased significantly after treatment from median 29.5 g/l (range 14.0-42.0 g/l) to 33.5 g/l (range 23.0-40.0 g/l) at follow-up (P = 0.04). There were no significant changes in serum creatinine (P = 0.55).. MMF is a potentially useful immunosuppressive agent in reducing the proteinuria associated with membranous predominant LN.

Topics: Adult; Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Middle Aged; Mycophenolic Acid; Proteinuria; Retrospective Studies; Severity of Illness Index; Treatment Outcome

Glomerular disease is an important cause of allograft loss. Treatment regimens for posttransplant glomerular disease are not well defined. Several reports have demonstrated that mycophenolate mofetil (MMF) is effective in treating native kidney glomerular disease. The effects of MMF are dose related. Therefore, we hypothesized that high-dose MMF (3 g/day) would be effective in treating glomerular disease in the allograft, minimizing the need for intravenous steroids and/or cyclophosphamide. This case series describes the results of the use of high-dose MMF in 6 patients.. High-dose MMF (3 g/day) was used to treat biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, proliferative lupus nephritis, and perinuclear antineutrophil cytoplasmic antibodies glomerulonephritis) in 6 renal transplant recipients. Patients were offered this treatment if they had failed or did not tolerate standard treatment regimens. Remission was defined by a decrease or stabilization of serum creatinine, decrease in proteinuria and, where applicable, improvement in immunological markers of disease.. All 6 patients had disease remission after starting MMF with the most common side effect being leukopenia, which responded to dose reduction.. High-dose MMF may be an effective agent in treating glomerular disease in the allograft.

Topics: Adult; Aged; Female; Glomerulonephritis; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Remission Induction

Topics: Female; Glomerulonephritis, Membranous; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Proteinuria; Treatment Outcome

Topics: Anti-Inflammatory Agents; Child, Preschool; Glomerulonephritis, Membranous; Granuloma, Plasma Cell; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisone; Skin Diseases

Eight patients with resistant and/or relapsing nephrotic syndrome or renal insufficiency were empirically treated with mycophenolate mofetil (MMF). The underlying glomerular diseases were membranous nephropathy (N = 3), minimal change disease (n = 2), focal segmental glomerulosclerosis (n = 1), and lupus nephritis (N = 2). Treatment with MMF 0.75 to 1.0 g twice daily, either as monotherapy or in combination with low-dose steroid treatment, resulted in substantial reductions in proteinuria or stabilization of serum creatinine. In relapsing patients following withdrawal from cyclosporin A, MMF achieved suppression of proteinuria equivalent to or better than that which occurred during cyclosporin A treatment. Steroids were successfully withdrawn in each of the non-lupus patients. MMF was well tolerated with no evidence of hematologic, hepatic, or other toxicity. These clinical anecdotes demonstrate the short-term clinical efficacy of MMF treatment. In addition, they suggest that MMF may have major steroid-sparing effects and might represent an alternative to cyclosporin A in appropriate patients.

Topics: Adult; Aged; Female; Glomerulonephritis; Glomerulonephritis, Membranous; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Lupus Nephritis; Male; Mycophenolic Acid; Nephrosis; Nephrosis, Lipoid

The effect of mycophenolate mofetil (MMF) was examined in active Heymann nephritis (HN), an animal model of human membranous nephropathy. HN was induced in Lewis rats with Fx1A/complete Freund's adjuvant (CFA), and controls only received CFA. The induction of HN was prevented by MMF (30 mg/kg per d) from 0 to 4 wk after immunization. Proteinuria was not different in CFA controls up to 16 wk, and was significantly less than in untreated HN from 6 wk onward. Serum anti-Fx1A antibody (Ab) levels and glomerular Ig deposition were suppressed during therapy. The interstitial infiltrate of alphabetaTCR+, CD4+ and CD8+ T cells, natural killer cells, and macrophages (mphi) observed in untreated HN at 8 wk was absent from rats treated from 0 to 4 wk with MMF. Semiquantitative reverse transcription-PCR for renal mononuclear cell cytokine mRNA at 8 wk demonstrated that MMF from 0 to 4 wk prevented the increased expression of Th1 (interferon-gamma, lymphotoxin), Th2 (interleukin-4), and mphi (tumor necrosis factor-alpha) cytokines identified in untreated HN. In lymph node draining sites of immunization, MMF limited both enlargement and the increased proportion of CD3+, CD4+, and CD8+ T cells observed in untreated HN and CFA controls. MMF suppressed Th2 (interleukin-4) but not Th1 (interferon-gamma, lymphotoxin) cytokine mRNA expression in lymph nodes. MMF from 4 to 8, 6 to 12, or 10 to 14 wk did not prevent proteinuria, serum anti-Fx1A Ab, or glomerular IgG deposition when compared with untreated HN. This study showed that MMF from 0 to 4 wk prevented the induction of HN and was associated with preferential suppression of Th2 cytokines. This therapy may prove useful in human idiopathic membranous nephropathy.

Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Glomerulonephritis; Glomerulonephritis, Membranous; Humans; Interferon-gamma; Interleukins; Kidney Cortex; Lymphokines; Male; Mycophenolic Acid; Proteinuria; Rats; Rats, Inbred Lew; RNA, Messenger; Th1 Cells; Th2 Cells; Tumor Necrosis Factor-alpha