mycophenolic-acid and Nephrosis--Lipoid

Steroids have been used widely since the early 1970s for the treatment of adult-onset minimal change disease (MCD). Recently, newer agents have been used in adult MCD aiming to reduce the risk of adverse effects. The response rates to immunosuppressive agents in adult MCD are more variable than in children. The optimal agent, dose, and duration of treatment for the first episode of nephrotic syndrome, or for disease relapse(s) have not been determined. This is an update of a review first published in 2008.. We aimed to 1) evaluate the benefits and harms of different agents, including both immunosuppressive and non-immunosuppressive agents, in adults with MCD causing the nephrotic syndrome; and 2) evaluate the efficacy of interventions on 'time-to-remission' of nephrotic syndrome, in adults with MCD causing the nephrotic syndrome.. We searched the Cochrane Kidney and Transplant Register of Studies up to 21 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.. Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for MCD with nephrotic syndrome in adults over 18 years were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.. Two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.. Fifteen RCTs (769 randomised participants) were identified; four studies evaluated different prednisolone regimens, eight studies evaluated the calcineurin inhibitors (CNIs) (tacrolimus or cyclosporin), two studies evaluated enteric-coated mycophenolate sodium (EC-MPS) and one study evaluated levamisole. In all but two studies of non-corticosteroid agents, reduced-dose prednisolone was given with the treatment agent and the comparator was high-dose prednisolone. In the risk of bias assessment, 11 and seven studies were at low risk of bias for sequence generation and allocation concealment, respectively. No studies were at low risk of performance bias and eight studies were at low risk of detection bias. Thirteen, 10 and six studies were at low risk of attrition bias, reporting bias and other bias, respectively. Compared with no specific treatment, it is uncertain whether prednisolone increases the number with complete remission (1 study, 28 participants: RR 1.44, 95% CI 0.95 to 2.19), complete or partial remission (1 study, 28 participants: RR 1.38, 95% CI 0.98 to 1.95), subsequent relapse (1 study, 28 participants: RR 0.75, 95% CI 0.48 to 1.17), or reduces the adverse effects because the certainty of the evidence is very low. Compared with oral prednisolone alone, it is uncertain whether intravenous methylprednisolone and prednisolone increase the number with complete remission (2 studies, 35 participants: RR 1.76, 95% CI 0.17 to 18.32; I² = 90%), relapse (two studies, 19 participants. RR 1.18, 95% CI 0.65 to 2.15; I² = 0%) or adverse events because the certainty of the evidence is very low. Compared with prednisolone alone, CNIs with reduced-dose prednisolone or without prednisolone probably make little or no difference to the number achieving complete remission (8 studies; 492 participants: RR 0.99, 95% CI 0.93 to 1.05; I² = 0%), complete or partial remission (4 studies, 269 participants: RR 1.01, 95% CI 0.96 to 1.05; I² = 0%), or relapse (7 studies; 422 participants: RR 0.73, 95% CI 0.51 to 1.03; I² = 0%) (moderate certainty evidence), may reduce the risk of obesity or Cushing's Syndrome (5 studies; 388 participants: RR 0.11, 95% CI 0.02 to 0.59; I² = 45%) and the risk of acne (4 studies; 270 participants: RR 0.15, 95% CI 0.03 to 0.67; I² = 0%) (low certainty evidence); and had uncertain effects on diabetes or hyperglycaemia, hypertension, and acute kidney injury (AKI) (low certainty evidence). Compared with prednisolone alone, EC-MPS with reduced-dos. This updated review has identified evidence for the efficacy and adverse effects of CNIs and EC-MPS with or without reduced-dose prednisolone compared with prednisolone alone for the induction of remission in adults with MCD and nephrotic syndrome with some reductions in steroid-associated adverse events. RCT data on the efficacy and adverse effects of rituximab in adults with MCD are awaited. Further, adequately powered RCTs are required to determine the relative efficacies of CNIs and EC-MPS and to evaluate these medications in patients with relapsing or steroid-resistant disease.

Topics: Acute Kidney Injury; Adult; Calcineurin Inhibitors; Child; Female; Humans; Immunosuppressive Agents; Levamisole; Male; Methylprednisolone; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Recurrence; Steroids

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

Topics: Abatacept; Antibodies, Monoclonal, Murine-Derived; Azathioprine; Combined Modality Therapy; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunoconjugates; Kidney Glomerulus; Lupus Nephritis; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Prognosis; Rituximab; Sjogren's Syndrome; Tonsillectomy

Steroid sensitive (minimal change) nephrotic syndrome (MCNS) has been regarded as immunological disorder because of clinical and experimental evidence as well as the response to immunosuppressive treatment. Recent work increased dramatically the understanding of podocyte biology which may be the key structure involved in MCNS, Interestingly many treatment options which were thought to work via an immunosuppressive pathway are now known to have a direct -non immunological- impact on the glomerular filtration barrier, i.e. the podocyte. Aim of this review is the presentation of recent research regarding the podocyte biology but also concerning the treatment of this disorder.

Topics: Antibodies, Monoclonal, Murine-Derived; Child; Cyclosporine; Evidence-Based Medicine; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Podocytes; Randomized Controlled Trials as Topic; Rituximab; Tacrolimus; Treatment Outcome

Few controlled trials have studied the treatment of relapse in adults with minimal change disease. Repeated courses of steroids, cyclophosphamide, cyclosporine and even mycophenolate mofetil (MMF), all seem to play a role. The aim of this study was to review and critically analyze the literature regarding the use of immunosuppressive therapy for the treatment of relapse in adults with minimal change nephrotic syndrome (MCNS). An intensive search was done for published trials in the general medical database. Retrieved studies were further sorted according to specific inclusion and exclusion criteria. Selected trials were critically analyzed and evaluated using the Oxford Centre for Evidence-based Medicine Levels of Evidence, 2009 rating. Six studies were selected and systematically reviewed. One randomized controlled trial compared the use of cyclo-phosphamide versus cyclosporine (11 adults) and showed that both drugs are effective in the treatment of frequent relapses [level 1b evidence (grade B)]. Three trials (total of 20 patients) tested the use of cyclosporine therapy and showed that cyclosporine, though effective in the treatment of relapse, is associated with an extremely high incidence of subsequent relapses following drug with-drawal. A long-term follow-up cross-sectional study of 95 patients, with 69 relapsers, supported the use of steroids in the treatment of occasional relapses [level 2c evidence (grade C)]. One case series described the benefits of MMF [level 4 evidence (grade C)]. Most of the the clinical trials studied were heterogeneous, underpowered by small adult populations, open-labelled, non-randomized, with poor statistical analysis, validity and utility. We conclude that there is poor evidence that successful treatment of the first relapse of adult MCNS can be achieved with a second course of steroids or cyclosporine. Also, there is weak evidence that frequent relapses can be treated using cyclophosphamide, cyclosporine or MMF. Powered, multi-centered, randomized, blinded, controlled trials, with long-term follow-up are required to know the optimal treatment for relapsing adult MCNS.

Topics: Adult; Cyclophosphamide; Cyclosporine; Evidence-Based Medicine; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Recurrence; Steroids; Treatment Outcome

Topics: Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Drug Resistance; Female; Glucocorticoids; Humans; Immunologic Factors; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Prednisone; Remission Induction; Rituximab; Time 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

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

Mycophenolate has been shown to be effective in glomerular disease. However, the role of mycophenolate in the first-line treatment of adult-onset idiopathic minimal change disease (MCD) has not been systematically studied in a randomized fashion.. To evaluate the therapeutic efficacy of enteric-coated mycophenolate sodium combined with low-dose corticosteroid as first-line treatment for MCNS.. A prospective, open-label, randomized clinical trial.. Twenty adult patients with biopsy proven MCD were recruited and randomly assigned to receive either enteric-coated Mycophenolate Sodium (EC-MPS) plus low-dose prednisolone (Group 1: Prednisolone 0.25 mg/kg/day, n = 10) or standard-dose prednisolone (Group 2: Prednisolone 1 mg/kg/day, n = 10).. After 24 weeks of therapy, eight patients in Group 1 vs. seven of patients in Group 2 achieved complete remission (P = 0.606). Both groups showed a significant reduction of urine protein excretion (P < 0.05) and increased serum albumin (P < 0.001) vs. baseline levels. However, no significant between-group differences were demonstrated. The relapse rate was also similar in both groups. Both treatment regimens were well tolerated but there were more patient reported adverse effects in the standard-dose prednisolone group.. EC-MPS plus low-dose prednisolone is non-inferior to standard-dose prednisolone therapy in inducing clinical remission and preventing relapse in adult-onset idiopathic MCD and is associated with better tolerability and less adverse effects. This trial is registered with the ClinicalTrials.gov number NCT01185197.

Topics: Adolescent; Adult; Aged; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Hong Kong; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Prednisolone; Prospective Studies; Recurrence; Remission Induction; Treatment Outcome; Young Adult

First-line therapy of minimal change nephrotic syndrome (MCNS) in adults is extrapolated largely from pediatric studies and consists of high-dose oral corticosteroids. We assessed whether a low corticosteroid dose combined with mycophenolate sodium was superior to a standard oral corticosteroid regimen. We enrolled 116 adults with MCNS in an open-label randomized controlled trial involving 32 French centers. Participants randomly assigned to the test group (n=58) received low-dose prednisone (0.5 mg/kg/day, maximum 40 mg/day) plus enteric-coated mycophenolate sodium 720 mg twice daily for 24 weeks; those who did not achieve complete remission after week 8 were eligible for a second-line regimen (increase in the prednisone dose to 1 mg/kg/day with or without Cyclosporine). Participants randomly assigned to the control group (n=58) received conventional high-dose prednisone (1 mg/kg/day, maximum 80 mg/day) for 24 weeks. The primary endpoint of complete remission after four weeks of treatment was ascertained in 109 participants, with no significant difference between the test and control groups. Secondary outcomes, including remission after 8 and 24 weeks of treatment, did not differ between the two groups. During 52 weeks of follow-up, MCNS relapsed in 15 participants (23.1%) who had achieved the primary outcome. Median time to relapse was similar in the test and control groups (7.1 and 5.1 months, respectively), as was the incidence of serious adverse events. Five participants died from hemorrhage (n=2) or septic shock (n=3), including 2 participants in the test group and 3 in the control group. Thus, in adult patients, treatment with low-dose prednisone plus enteric-coated mycophenolate sodium was not superior to a standard high-dose prednisone regimen to induce complete remission of MCNS.

Topics: Adult; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Prospective Studies; Remission Induction; Treatment Outcome

Soluble urokinase-type plasminogen activator receptor (suPAR) could be a causative factor in idiopathic focal segmental glomerulosclerosis (FSGS). It is currently unknown to what extent suPAR levels could be affected by treatment with immunosuppressive drugs such as cyclosporin A (CsA) and mycophenolate mofetil (MMF). Treatment with CsA, but not MMF, is accompanied by nephrotoxicity, and since suPAR levels correlate with glomerular filtration rate (GFR), treatment with these drugs could indirectly modulate suPAR levels by their effect on renal function.. We measured suPAR levels in a recent prospective multicenter crossover trial comparing the efficacy of MMF and CsA in pediatric patients with minimal change disease (MCD) and frequently relapsing steroid-sensitive nephrotic syndrome (FR-SSNS). All patients had biopsy-proven MCD and normal renal function; they were treated with each drug for 1 year in a crossover study design. Serum suPAR levels were measured before and after 1 year of therapy with MMF (n = 40) and CsA (n = 35).. The suPAR levels decreased after 1 year of treatment with MMF (p < 0.05). Conversely, suPAR levels increased after 1 year of treatment with CsA in the same patients (p = 0.01). These changes in suPAR levels were not correlated to the estimated glomerular filtration rate (eGFR) or changes in the GFR.. Data from this prospective randomized trial suggest that treatment with MMF and CsA is associated with different effects on suPAR levels in children with MCD and that these are independent of their effects on GFR.

Topics: Adolescent; Child; Child, Preschool; Cross-Over Studies; Cyclosporine; Female; Glomerular Filtration Rate; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrosis, Lipoid; Receptors, Urokinase Plasminogen Activator

We performed a multi-centre randomized controlled trial to compare the efficacy of mycophenolate mofetil (MMF) to that of cyclosporine A (CsA) in treating children with frequently relapsing nephrotic syndrome and biopsy-proven minimal change disease. Of the 31 randomized initially selected patients, seven were excluded. The remaining 24 children received either MMF 1200 mg/m(2) per day (n = 12) or CsA 4-5 mg/kg per day (n = 12) during a 12-month period. Of the 12 patients in the MMF group, two discontinued the study medication. Evaluation of the changes from the baseline glomerular filtration rate showed an overall significant difference in favour of MMF over the treatment period (p = 0.03). Seven of the 12 patients in the MMF group and 11 of the 12 patients in the CsA group remained in complete remission during the entire study period. Relapse rate in the MMF group was 0.83/year compared to 0.08/year in the CsA group (p = 0.08). None of the patients reported diarrhea. Pharmacokinetic profiles of mycophenolic acid were performed in seven patients. The patient with the lowest area under the curve had three relapses within 6 months. In children with frequently relapsing minimal change nephrotic syndrome, MMF has a favourable side effect profile compared to CsA; however, there is a tendency towards a higher relapse risk in patients treated with MMF.

Topics: Adolescent; Biopsy; Blood Pressure; Child; Child, Preschool; Cyclosporine; Disease-Free Survival; Female; Gingival Hyperplasia; Glomerular Filtration Rate; Humans; Hypertrichosis; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrosis, Lipoid; Remission Induction; Secondary Prevention; Treatment Outcome

A small proportion of patients with initially steroid-sensitive nephrotic syndrome relapse frequently, despite treatment with cyclophosphamide and/or cyclosporin. We investigated the efficacy of mycophenolate mofetil (MMF) in this group.. Seven patients with nephrotic syndrome due to minimal change nephropathy (MCN) or classical focal segmental glomerulosclerosis (FSGS) who had suffered multiple relapses over many years despite treatment with several different agents were commenced on MMF 1 g twice daily, together with a reducing dose of corticosteroids.. Six patients went into complete remission and the seventh into partial remission. At 1 year, five remained in complete remission. The median (range) serum albumin concentration rose from 19 g/l (16-42 g/l) pre-MMF to 42 g/l (25-45 g/l) after 12 months (P=0.023), and the median (range) dose of prednisolone fell from 40 mg/day (30-60 mg/day) to 7.5 mg/day (0-40 mg/day) at 12 months (P=0.0008).. MMF appears to be of benefit in the treatment of multiply relapsing nephrotic syndrome caused by MCN or FSGS. Controlled trials are required to establish the role of MMF in these disorders.

Topics: Adult; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisolone; Recurrence; Remission Induction; Serum Albumin

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

There seems to be a possible link between nephrotic syndrome (NS) and lymphoproliferative syndrome, but it remains poorly understood.. This multicentric and retrospective study focuses on children, who developed idiopathic NS and malignant or benign proliferation between 2000 and 2021.. Eleven patients were included, with a median age of 4 years. Only one had a steroid-resistant nephrotic syndrome (SRNS). The maintenance therapy before the proliferation was in majority tacrolimus or mycophenolate mofetil (MMF), but three patients did not receive treatments. The proliferation was mainly a Hodgkin's lymphoma (45%) or a lymphoproliferative disease (36%), in a median time after the NS of two years. Viruses were found in seven cases (EBV in five cases and HHV-8 in two).. The association between proliferative syndrome and idiopathic NS may not be fortuitous, possibly with a common lymphocytic disturbance. Genetic analyses could improve the comprehension of these manifestations in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

Topics: Cell Proliferation; Child, Preschool; Cohort Studies; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Remission Induction; Retrospective Studies; Treatment Outcome

A 3-year-old entire female Springer Spaniel, with a previous diagnosis of meningoencephalitis of unknown origin diagnosed 2 years before presentation and treated with long term administration of prednisolone, developed proteinuria. Laboratory findings revealed hypoalbuminemia, hypercholesterolemia, and proteinuria. Further investigations excluded underlying causes. Renal biopsies were performed. The glomeruli and the tubulointerstitial compartment did not show any anomalies on light microscopy and immunofluorescence staining did not reveal abnormalities. Transmission electron microscopy revealed moderate podocyte injury consisting of foot process effacement and microvillus transformation of the cytoplasm. The dog was diagnosed with primary minimal change disease of the podocytes and treated with telmisartan and mycophenolate mofetil. Abnormalities of serum albumin, cholesterol, and proteinuria resolved within 4 weeks. Minimal change disease has been reported in dogs, but this is a case report of proteinuria secondary to minimal change disease successfully treated with mycophenolate mofetil and telmisartan.

Topics: Animals; Dog Diseases; Dogs; Female; Kidney Glomerulus; Mycophenolic Acid; Nephrosis, Lipoid; Proteinuria; Telmisartan

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 comparing all treatment options for frequently-relapsing/steroid-dependent (FR/SD) minimal change disease (MCD) in adults are lacking.. Medical records of 76 adults with FR/SD MCD who were treated with corticosteroids as the first-line therapy were reviewed. Treatment options were compared for the time to relapse, change of therapy and progression (relapse on full-dose treatment).. Second-line treatments included rituximab (RTX; n = 13), mycophenolate mofetil (MMF; n = 12), calcineurin inhibitors (CNI; n = 26) and cyclophosphamide (CTX; n = 16). During the second-line treatments, 48 (71.6%) patients relapsed at median 17 (range 2-100)  months. The majority of relapses occurred during dose tapering or off drug. Twenty of 65 (30.8%) changed therapy after the first relapse. The median time to relapse after the second line was 66 versus 28 months in RTX versus non-RTX groups (P = 0.170). The median time to change of treatment was 66 and 44 months, respectively (P = 0.060). Last-line treatment options included RTX (n = 8), MMF (n = 4), CNI (n = 3) and CTX (n = 2). Seven (41.2%) patients had a relapse during the last-line treatment at median 39 (range 5-112)  months. The median time to relapse was 48 versus 34 months in the RTX versus non-RTX groups (P = 0.727). One patient in the RTX group died presumably of heart failure. No major adverse event was observed. During the median follow-up of 81 (range 9-355)  months, no patients developed end-stage renal disease.. Relapse is frequent in MCD in adults. Patients treated with RTX may be less likely to require a change of therapy and more likely to come off immunosuppressive drugs.

Topics: Adult; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid; Recurrence; Rituximab; Steroids; Treatment Outcome

Idiopathic nephrotic syndrome (NS) is common in children, and most patients respond to corticosteroid therapy. Patients who relapse may need additional immunosuppression with cyclophosphamide, mycophenolate mofetil, calcineurin inhibitors (CNI), or rituximab. Many such patients undergo protocol renal biopsies before and after the initiation of CNI therapy. The main objective of our study was to assess the role of protocol renal biopsies in the monitoring of CNI-induced nephrotoxicity in patients with steroid-dependent (SD)/frequent relapse (FR) NS. We did an Institutional Review Board (IRB)-approved retrospective chart review of patients who were diagnosed with NS at the Children's Hospital of Michigan from January 2000 to June 2019. Study inclusion criteria were a diagnosis of NS, age 1 - 21 years at initial diagnosis, SD/FR clinical course, patients with initial steroid resistance with renal biopsy showing minimal change disease, and renal biopsy before and after CNI initiation. The data is presented on 24 patients who met study inclusion criteria. Only 3 patients (12.5%) showed evidence of chronic CNI nephrotoxicity after a median treatment 66.5 months (range 12 - 153 months). Our study revealed that a baseline renal biopsy before starting CNI therapy for children with FR/SDNS is not necessary. A renal biopsy may be considered after 2 - 3 years of CNI administration in selected few cases in whom the diagnosis of CNI nephrotoxicity might help change the management.

Topics: Adolescent; Adult; Biopsy; Calcineurin Inhibitors; Child; Child, Preschool; Humans; Immunosuppressive Agents; Infant; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Retrospective Studies; Treatment Outcome; Young Adult

Although recent studies have shown that more than half of children with steroid-dependent nephrotic syndrome (SDNS) may continue to have active disease beyond childhood, the long-term outcome in this cohort treated with mycophenolate mofetil (MMF) after cyclosporine remains unknown, particularly in adulthood.. We conducted a retrospective study of 44 adult patients (median age, 22.3 years) who received MMF for complicated SDNS (median age at MMF initiation, 13.3 years) at a single center. Complicated SDNS was defined as the case continuing to relapse after cyclosporine (CsA) treatment. When patients experienced relapses despite MMF initiation, they additionally received a rituximab infusion. The primary endpoint was the probability of achieving treatment-free remission for > 2 years.. Prior to MMF initiation, all patients received CsA for a median of 46 months and 19 received the 12-week cyclophosphamide. After switching from CsA to MMF, only four patients did not relapse during a median follow-up period of 9.6 years. At the last visit, only 15 of the 44 patients achieved treatment-free sustained remission. Multivariate analysis revealed that young age (< 6 years) at onset of nephrotic syndrome (odds ratio, 11.3) and the experience of steroid dependency during initial CsA treatment (odds ratio, 29.8) were the independent risk factors of active disease into adulthood after MMF initiation.. Although none developed renal insufficiency and severe adverse effects of therapy, the introduction of MMF after CsA treatment may not be necessarily associated with improved long-term outcome of children with complicated SDNS.

Topics: Adolescent; Child; Child, Preschool; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Japan; Longitudinal Studies; Male; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Recurrence; Remission Induction; Retrospective Studies; Rituximab; Secondary Prevention; Time Factors; Treatment Outcome; 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

Rare cases of association between lupus nephritis (LN) and minimal changes nephrotic syndrome (MCNS) were described. Some authors suggest that this association, taking into account the low prevalence of both diseases, may not be a simple coincidence. Several pathophysiological hypotheses have been proposed to explain this association, including a potential central role of T lymphocytes.. We describe the case of a 21 years-old female patient who initially presented with isolated nephrotic range proteinuria. She had no evidence of systemic involvement and Immunological tests were negative, including anti-neutrophil antibodies (ANA) and anti-double-stranded DNA antibodies (Anti-dsDNA). Renal biopsy showed normal glomeruli under light microscopy and no significant deposits were found in immunofluorescence studies. She was diagnosed to have MCNS and responded to a short course of steroids. She remained in remission for three years, after which she presented again with nephrotic-range proteinuria accompanied by clinical signs of systemic involvement. During her second presentation, she fulfilled the diagnostic criteria of systemic lupus erythematosus (SLE) and another kidney biopsy showed class-V lupus nephritis. She was treated with pulse steroids followed by oral prednisolone and mycophenolate mofetil, with good clinical response.. This case indicates that relapses of MCNS should be carefully investigated in the right setting to avoid missing a systemic disease such as SLE.

Topics: Antibodies, Antinuclear; Female; Humans; Lupus Erythematosus, Systemic; Lupus Nephritis; Mycophenolic Acid; Nephrosis, Lipoid; Prednisolone; Proteinuria; Young Adult

The World Health Organization classifies lupus nephritis as class I to V or VI. However, a few cases of minimal change glomerulopathy have been reported in association with systemic lupus erythematosus (SLE). Mycophenolate mofetil has been shown to be effective for treatment of minimal change disease and lupus nephritis. A 24-year-old woman diagnosed with SLE five years prior to presentation complained of a mild generalized edema. The urinalysis showed microscopic hematuria and proteinuria. The assessed amount of total proteinuria was 1,618 mg/24 hours. A renal biopsy demonstrated diffuse fusion of the foot processes of podocytes on electron microscopy. Mycophenolate mofetil was started in addition to the maintenance medications of prednisolone 10 mg/day and hydroxychloroquine 400 mg/day. After six months of treatment, the microscopic hematuria and proteinuria resolved, and the total urine protein decreased to 100 mg/24 hours.

Topics: Antirheumatic Agents; Female; Glucocorticoids; Humans; Hydroxychloroquine; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Mycophenolic Acid; Nephrosis, Lipoid; Prednisone; Young Adult

Topics: Adolescent; Female; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrosis, Lipoid

C1q nephropathy (C1qN) is an uncommon disorder seen in children and adults with nephrotic syndrome and non-specific urinary findings. It has been described with minimal change nephrotic syndrome (MCNS), focal segmental glomerulonephritis and isolated mesangial proliferative glomerulonephritis. We describe nine children with MCNS and mesangial C1q deposition. These children had a median age of 2.7 years at diagnosis (range 1.3-15 years), 56% were male and 78% were Hispanic. We compared these children to concurrent patients with nephrotic syndrome and biopsy-proven MCNS. We found that the C1qN patients were more likely than MCNS children to require chronic immunosuppression with calcineurin inhibitors or mycophenolate mofetil to maintain remission. However, all children were able to achieve and sustain clinical remission of nephrotic syndrome. Children with C1qN and minimal change histology have an increased frequency of frequently relapsing and steroid-unresponsive disease, but they can attain prolonged remission and stable renal function with calcineurin inhibitor or mycophenolate mofetil therapy.

Topics: Adolescent; Calcineurin Inhibitors; Child; Child, Preschool; Cohort Studies; Complement C1q; Drug Therapy, Combination; Female; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Infant; Male; Mycophenolic Acid; Nephrosis, Lipoid; Prednisolone; Retrospective Studies

Among the causes of the nephrotic syndrome in renal allografts, minimal change disease is a rarity with only few cases described in the medical literature. Most cases described have occurred early in the post-transplant course. There is no established treatment for the condition but prognosis is favorable. We describe a case of minimal change disease that developed 8 years after a successful transplantation of a renal allograft in a middle-aged woman. The nephrotic syndrome was accompanied by deterioration of allograft function. Treatment with mycophenolate mofetil was successful in inducing remission and stabilizing allograft function.

Topics: Biopsy; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Glomerulus; Kidney Transplantation; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Prodrugs; Remission Induction; Time Factors; Transplantation, Homologous

The therapeutic approach to childhood nephrotic syndrome is based on a series of studies that began with an international collaborative effort sponsored by the International Study of Kidney Disease in Children in 1967. The characteristics of children presenting with nephrotic syndrome have changed over recent decades with greater frequency of the challenging condition focal segmental glomerulosclerosis and a greater prevalence of obesity and diabetes mellitus, which may be resistant to glucocorticoids in the former and exacerbated by long-term glucocorticoid therapy in the latter 2 conditions. The Children's Nephrotic Syndrome Consensus Conference was formed to systematically review the published literature and generate a children's primary nephrotic syndrome guideline for use in educational, therapeutic, and research venues.

Topics: Antineoplastic Agents; Biopsy; Child; Combined Modality Therapy; Cyclophosphamide; Cyclosporine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Resistance; Drug Therapy, Combination; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney; Kidney Function Tests; Mycophenolic Acid; Nephrosis, Lipoid; Nephrotic Syndrome; Prednisone

C1q nephropathy (C1qNP) is a rare cause of childhood nephrotic syndrome (NS). We describe a child with retinoblastoma, lipomyelomeningocele and a chromosome 13 deletion who presented with massive proteinuria due to C1qNP. Despite steroid resistance, successful treatment of the NS was achieved with mycophenolate mofetil.

Topics: Child; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 13; Complement C1q; Female; Humans; Immunosuppressive Agents; Meningomyelocele; Mycophenolic Acid; Nephrosis, Lipoid; Retinal Neoplasms; Retinoblastoma

Most patients with minimal change nephrotic syndrome are steroid responsive and tolerate this medication. However, a substantial number of patients relapse frequently and become steroid dependent. These patients often require treatment with alternative immunosuppressive drugs to maintain remission and minimize steroid toxicity. Previous studies have suggested that mycophenolate mofetil is effective in treating these patients. However, there are limited data on the effectiveness of this agent in pediatric patients, specifically those with steroid-dependent nephrotic syndrome. The purpose of this study was to assess the efficacy and safety of mycophenolate mofetil therapy in children and adolescents with steroid-dependent nephrotic syndrome who failed other treatments. A retrospective chart review was performed on all patients with steroid-dependent nephrotic syndrome. Clinical characteristics, laboratory data and the relapse rate were assessed prior to and during mycophenolate mofetil treatment. Twenty-one patients, ages 2-17 years, with steroid-dependent nephrotic syndrome who were treated with mycophenolate mofetil between 2001-2005 were included in this review. The indication for mycophenolate mofetil use was steroid dependence in 17 and steroid toxicity in 4 patients. The mean duration of treatment was 1.0+/-0.5 years (range: 0.2-2.0 years). Patients treated with mycophenolate mofetil had a reduction in relapse rate from 0.80+/-0.41 to 0.47+/-0.43 relapses per month ( P <0.02). Side effects were mild and mostly gastrointestinal in nature. In 1 child, mycophenolate mofetil was discontinued due to varicella infection and not restarted. The findings indicate that mycophenolate mofetil is a useful adjunctive therapy in the treatment of patients with steroid-dependent nephrotic syndrome. It lowers the relapse rate by 40% and is well tolerated by patients with steroid-dependent nephrotic syndrome.

Topics: Adolescent; Adrenal Cortex Hormones; Child; Child, Preschool; Female; Humans; Immunosuppressive Agents; Infant; Male; Mycophenolic Acid; Nephrosis, Lipoid; Prednisone; Retrospective Studies; Treatment Outcome

We report 4 consecutive adult patients with steroid-responsive frequently relapsing minimal change disease (MCD) who continued to experience relapse after 1 to 4 courses of cyclophosphamide therapy. Each patient then was administered mycophenolate mofetil (MMF) and prednisone in tapering doses. This therapy was followed by sustained remission and is being well tolerated. MMF is promising therapy in frequently relapsing MCD, even in those with disease that continued to relapse after cyclophosphamide therapy. A controlled clinical trial of MMF therapy in this disorder is warranted.

Topics: Adult; Cyclophosphamide; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Nephrosis, Lipoid; Recurrence

Here we report two male patients, 16 and 20 years-old respectively, with minimal-change nephrotic syndrome showing frequent relapses and steroid dependence. Treatment with cyclosporin did not prevent the appearance of new relapses and both patients developed cyclosporin-dependence. The introduction of mycophenolate mofetil (500-15,000 mg/day) was followed by a sustained complete remission in both cases, without secondary effects.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrosis, Lipoid

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