mycophenolic-acid and Glomerulosclerosis--Focal-Segmental

Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and secondary forms may be associated with asymptomatic proteinuria or with nephrotic syndrome. Overall only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome with treatment. FSGS progresses to kidney failure in about half of the cases. This is an update of a review first published in 2008.. To assess the benefits and harms of immunosuppressive and non-immunosuppressive treatment regimens in adults with FSGS.. We searched the Cochrane Kidney and Transplant Register of Studies to 21 June 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 FSGS in adults were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.. At least 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 studies (560 participants) were included. No studies specifically evaluating corticosteroids compared with placebo or supportive therapy were identified. Studies evaluated participants with steroid-resistant FSGS. Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan. In the risk of bias assessment, seven and five studies were at low risk of bias for sequence generation and allocation concealment, respectively. Four studies were at low risk of performance bias and 14 studies were at low risk of detection bias. Thirteen, six and five studies were at low risk of attrition bias, reporting bias and other bias, respectively. Of five studies evaluating cyclosporin, four could be included in our meta-analyses (231 participants). Cyclosporin with or without prednisone compared with different comparators may increase the likelihood of complete remission (RR 2.31, 95% CI 1.13 to 4.73; I² = 1%; low certainty evidence) and of complete or partial remission (RR 1.64, 95% CI 1.10 to 2.44; I² = 19%) but not of partial remission (RR 1.36, 95% CI 0.78 to 2.39, I² = 22%). In Individual studies, cyclosporin with prednisone versus prednisone may increase the likelihood of partial (49 participants: RR 7.96, 95% CI 1.09 to 58.15) or complete or partial remission (49 participants: RR 8.85, 95% CI 1.22 to 63.92) but not of complete remission. The remaining individual comparisons may make little or no difference to the likelihood of complete remission, partial remission or complete or partial remission compared with no treatment, methylprednisolone, MMF, or dexamethasone. Individual study data and combined data showed that cyclosporin may make little or no difference to the outcomes of chronic kidney disease or kidney failure. It is uncerta. No RCTs, which evaluated corticosteroids, were identified although the KDIGO guidelines recommend corticosteroids as the first treatment for adults with FSGS. The studies identified included participants with steroid-resistant FSGS. Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision due to few studies and small participant numbers. In future studies of existing or new interventions, the investigators must clearly define the populations included in the study to provide appropriate recommendations for patients with primary, genetic or secondary FSGS.

Topics: Adult; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Randomized Controlled Trials as Topic

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

Chronic kidney disease (CKD) is increasingly recognized in pregnant patients. Three characteristics are associated with a risk of preterm delivery or small for gestational age babies; kidney function reduction, hypertension, and proteinuria. In pregnancy, the anti-proteinuric agents (ACE-angiotensin converting enzyme-inhibitors or ARBS -angiotensin receptor blockers) have to be discontinued for their potential teratogenicity, and there is no validated approach to control proteinuria. Furthermore, proteinuria usually increases as an effect of therapeutic changes and pregnancy-induced hyperfiltration. Based on a favourable effect of low-protein diets on proteinuria and advanced CKD, our group developed a moderately protein-restricted vegan-vegetarian diet tsupplemented with ketoacids and aminoacids for pregnant patients. This report describes the results obtained in three pregnant patients with normal renal function, nephrotic or sub-nephrotic proteinuria, and biopsy proven diagnosis of focal segmental glomerulosclerosis, a renal lesion in which hyperfiltration is considered of pivotal importance (case 1: GFR (glomerular filtration rate): 103 mL/min; proteinuria 2.1 g/day; albumin 3.2 g/dL; case 2: GFR 86 mL/min, proteinuria 3.03 g/day, albumin 3.4 g/dL; case 3: GFR 142 mL/min, proteinuria 6.3 g/day, albumin 3.23 g/dL). The moderately restricted diet allowed a stabilisation of proteinuria in two cases and a decrease in one. No significant changes in serum creatinine and serum albumin were observed. The three babies were born at term (38 weeks + 3 days, female, weight 3180 g-62th centile; 38 weeks + 2 days, female, weight 3300 g-75th centile; male, 38 weeks + 1 day; 2770 g-8th centile), thus reassuring us of the safety of the diet. In summary, based on these three cases studies and a review of the literature, we suggest that a moderately protein-restricted, supplemented, plant-based diet might contribute to controlling proteinuria in pregnant CKD women with focal segmental glomerulosclerosis. However further studies are warranted to confirm the potential value of such a treatment strategy.

Topics: Adult; Amino Acids; Biomarkers; Biopsy; Black People; Cyclophosphamide; Cyclosporine; Diet, Protein-Restricted; Diet, Vegan; Diet, Vegetarian; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Keto Acids; Kidney; Male; Mycophenolic Acid; Pregnancy; Proteinuria; Renal Insufficiency, Chronic; White People

Recent advances show that human focal segmental glomerulosclerosis (FSGS) is a primary podocytopathy caused by podocyte-specific gene mutations including NPHS1, NPHS2, WT-1, LAMB2, CD2AP, TRPC6, ACTN4 and INF2. This review focuses on genes discovered in the investigation of complex FSGS pathomechanisms that may have implications for the current FSGS classification scheme. It also recounts recent recommendations for clinical management of FSGS based on translational studies and clinical trials. The advent of next-generation sequencing promises to provide nephrologists with rapid and novel approaches for the diagnosis and treatment of FSGS. A stratified and targeted approach based on the underlying molecular defects is evolving.

Topics: Actinin; Adalimumab; Adaptor Proteins, Signal Transducing; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cytoskeletal Proteins; Formins; Glomerulosclerosis, Focal Segmental; High-Throughput Nucleotide Sequencing; Humans; Immunologic Factors; Immunosuppressive Agents; Intracellular Signaling Peptides and Proteins; Laminin; Membrane Proteins; Microfilament Proteins; Molecular Targeted Therapy; Mycophenolic Acid; Plasmapheresis; Rituximab; TRPC Cation Channels; TRPC6 Cation Channel; WT1 Proteins

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

Focal segmental glomerulosclerosis (FSGS) is a pathologic condition that represents many disease entities. The goals of therapy are to cure the disease. When this is not possible, the secondary goals are to reduce proteinuria to avoid the complications of nephrotic syndrome and to delay progression of kidney disease. Proteinuria remission is one of the most important independent predictors of kidney survival. Children with FSGS who do not achieve partial or complete remission have a 50% risk of progression to ESRD within 5 years whereas those who enter complete remission have a 5-year kidney survival rate of 90%. Treatment of idiopathic FSGS commonly involves immune-based and nonimmunologic therapy options. This manuscript will review the current state of FSGS therapy for children.

Topics: Adrenal Cortex Hormones; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal, Murine-Derived; Antihypertensive Agents; Child; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Hypertension; Immunosuppressive Agents; Mycophenolic Acid; Obesity; Rituximab; Tacrolimus; Treatment Outcome; Vitamin D Deficiency

Focal segmental glomerulosclerosis (FSGS) is the histologic end point of many disease processes that affect the kidney. Clinically, adults with FSGS present with proteinuria that may be accompanied by the nephrotic syndrome. Once identifiable (secondary) causes are excluded, the diagnosis of idiopathic FSGS, a challenging glomerular disease to understand and manage, is made. On the basis of mostly retrospective data, first-line treatment for idiopathic FSGS patients with nephrotic-range proteinuria is a prolonged course of corticosteroids. However, steroid resistance is common and portends an increased risk of long-term decline in kidney function and end-stage kidney disease in these patients compared with responders. Multiple other immunosuppression regimens have been used in steroid-resistant FSGS, some of which have been studied in randomized controlled trials. Here, we review the data on the treatment for idiopathic FSGS in adults.

Topics: Adult; Angiotensin II Type 2 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Hypertension; Immunosuppressive Agents; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Treatment Outcome

Idiopathic focal and segmental glomerular sclerosis is a frequent cause of nephrotic syndrome and end-stage renal disease. The pathogenesis is still unknown, although the body of evidence suggests that focal and segmental glomerular sclerosis is caused by a not clearly identified circulating factor that alters the permselectivity of the glomerular barrier. Proteinuria is followed by podocyte injury. Glucocorticoids, calcineurin inhibitors, cytotoxic agents and mycophenolate mofetil, either given alone or in combination, may obtain complete or partial remission of proteinuria in 50-60% of patients and protect them from end-stage renal disease, but the remaining patients are resistant to the available drugs. A number of new drugs, including rituximab, galactose and antifibrotic agents, are under investigation.

Topics: Adult; Antibodies, Monoclonal, Murine-Derived; Calcineurin Inhibitors; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Kidney Failure, Chronic; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Rituximab

We report a case of pediatric severe aplastic anemia (SAA), where the patient underwent allogenic bone marrow transplantation (BMT) from an HLA mismatched family donor and developed focal segmental glomerulosclerosis (FSGS). An 11-year-old girl, who had SAA, was admitted to our hospital in 200X. Complete remission was not attained after immunosuppressive therapy with rabbit-antithymocyte globulin, prednisolone (PSL), and cyclosporine A (CsA). Eight months after being diagnosed with SAA, she underwent an allogenic BMT from her mother. We used a combination of 2-Gy total body irradiation, fludarabine, and cyclophosphamide as a preparative regimen prior to the BMT. CsA and PSL were used as prophylaxis against GVHD. Since the BMT did not lead to successful engraftment, the patient required two peripheral blood stem cell transplantations (PBSCT). Engraftment was sustained and no acute or chronic GVHD was observed. Six months after the first BMT, she developed clinical nephrotic syndrome despite the continuous PSL and CsA treatments. Renal biopsy revealed a total of 12 glomeruli, one of which showed segmental sclerosis. Electron microscopy revealed diffuse effacement of the foot processes. These findings were consistent with FSGS, and she was treated with mycophenolate mofetil (MMF) in combination with PSL instead of CsA, which greatly reduced her proteinuria. In general, the most common type of nephropathy after HSCT is GVHD-related nephrotic syndrome, and the most common pathological finding is membranous nephropathy or minimal change. FSGS without GVHD after HSCT, such as that observed in our case, is rare. In this case, the renal damage appears to have been caused by the effect of circulating permeability factors with immunity change after HSCT. This case demonstrates the importance of renal biopsy as a guide to determine the extent of renal damage and as an aid to determine the possible response to therapy.

Topics: Anemia, Aplastic; Biopsy; Child; Cyclosporine; Female; Glomerulosclerosis, Focal Segmental; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Kidney Glomerulus; Microscopy, Electron; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Treatment Outcome

Current treatments for primary focal segmental glomerulosclerosis (FSGS), including corticosteroids and cyclosporine, are not satisfactory for all patients and may induce significant side effects. Antidotal benefits of mycophenolate mofetil (MMF) as an add-on to these immunosuppressive therapies have been reported. This review aims to systematically summarize the efficacy and safety of MMF as a treatment for primary FSGS.. Controlled and uncontrolled clinical trials evaluating the use of MMF in primary FSGS patients were identified from nine electronic databases and four clinical trial registries. Kidney failure was selected as the primary outcome.. Three randomized controlled trials (RCT) and 18 uncontrolled pre-post studies were included. Results from RCTs revealed that MMF is no more effective than cyclosporine or cyclophosphamide for promoting kidney function preservation when corticosteroid is used as baseline treatment. One underpowered RCT reported that MMF provides no extra benefit on top of prednisolone, but the result is unlikely to be reliable. Amongst the small, uncontrolled pre-post studies, three of them used MMF as monotherapy, two of which reported successful prevention of kidney failure in all patients. The remaining 15 uncontrolled studies used MMF as add-on therapy and 11 reported kidney failure as an outcome. Amongst them, eight reported no patients developed kidney failure. MMF was generally well tolerated with mild adverse effects, including abdominal discomfort, diarrhea and infections.. MMF tended to show beneficial effects in uncontrolled studies which recruited patients with resistance to routine treatments, but such favorable results have only been reported in small, uncontrolled trials. No RCT results suggested that MMF was a good alternative to cyclosporine or cyclophosphamide. The role of MMF as an add-on to current therapies, or as monotherapy, should further be evaluated.

Topics: Controlled Clinical Trials as Topic; Glomerulosclerosis, Focal Segmental; Humans; Mycophenolic Acid; Randomized Controlled Trials as Topic; Treatment Outcome

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

Idiopathic nephrotic syndrome in children is commonly associated with minimal change disease and response to steroid therapy. Steroid-unresponsive nephrotic syndrome is often characterized by persistent proteinuria and progression to chronic kidney disease. Focal segmental glomerulosclerosis is the leading cause of steroid-unresponsive nephrotic syndrome in childhood. There is no uniformed consensus as to the treatment of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis, genetics and biomarkers or surrogate markers may be useful for the diagnosis and identification of patients with steroid-unresponsive nephrotic syndrome, severity of disease, progression and response to therapy.. This review is intended to describe some of the recent changes in the epidemiology of steroid-unresponsive nephrotic syndrome, in particular focal segmental glomerulosclerosis, its pathogenesis and alternative therapies.. Recent studies in both children and adults have shown an increase in the incidence of focal segmental sclerosis as a cause of steroid-unresponsive nephrotic syndrome. Advances in the pathogenesis and noninvasive methods of diagnosis may allow for the identification of steroid-responsive patients.

Topics: Child; Cyclosporins; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrotic Syndrome; Randomized Controlled Trials as Topic; Sirolimus; Tacrolimus; Treatment Outcome

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

Focal segmental glomerulosclerosis (FSGS) is not a disease, but a lesion affecting the podocyte. Secondary FSGS may be due to a host of various factors, and patients are rarely nephrotic, requiring symptomatic treatment only. The best prognostic feature of nephrotic FSGS is its response to corticosteroids. Some forms are most likely of immunological origin, relapse in a renal transplant and justify immunosuppressive treatment. In a growing number of cases, genetic profiling of molecules that contribute to the podocyte slit diaphragm permselectivity to albumin has identified defects that do not represent indications for immunosuppression. In the other forms, corticosteroids and cyclosporin A (CsA) remain the mainstay of treatment, with better efficacy when CsA is associated with steroids. The renal tolerability of CsA is reasonably good when the dosage is low. CsA dependency is not constant. Alkylating agents are reluctantly indicated in steroid-sensitive forms, which are rare. They are mostly ineffective in steroid-resistant forms. Tacrolimus seems a promising therapy with low toxicity, but it is usual for dependency on the drug to occur. Sirolimus seems to be ineffective. Azathioprine is not considered indicated, despite rare reports with favourable results, which would deserve further controlled trials. Recent publications indicate that mycophenolate mofetil might usefully find a place in the treatment. Plasmapheresis is of no avail outside the special case of relapse in a transplanted kidney. Immunoabsorption of the elusive substance that causes the nephrotic syndrome and its relapse on a transplant has not led to practical treatment options.

Topics: Alkylating Agents; Antimetabolites; Azathioprine; Contraindications; Cyclophosphamide; Cyclosporine; Drug Resistance; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunophilins; Immunosuppressive Agents; Mycophenolic Acid; Nephrotic Syndrome; Podocytes; Randomized Controlled Trials as Topic; Tacrolimus

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

Topics: Animals; Child; Cyclosporine; Cytotoxicity, Immunologic; Genes, Wilms Tumor; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrotic Syndrome; Plasmapheresis; Renin

A prolonged course with corticosteroids represents the first therapeutic approach for nephrotic patients with focal segmental glomerulosclerosis (FSGS). In patients with contraindications to steroids or in those who do not respond to steroids or cyclosporine, cytotoxic agents, mycophenolate mofetil (MMF), plasmapheresis, and low-density lipoprotein (LDL) apheresis have been tried as alternative treatments. A short-term treatment with cytotoxic agents often is ineffective in steroid-resistant patients However, an aggressive and prolonged treatment with cytotoxic agents combined with corticosteroids proved to be effective in more than half of steroid-resistant children. In adults, the response to cytotoxic agents was good in steroid-responsive patients, but was poor in steroid-resistant patients. Better results were observed when cytotoxic therapy was prolonged for several months. The problem with these drugs is that long-term immunosuppression may be complicated by severe side effects including a major risk for cancer. Uncontrolled studies reported that MMF can induce some reduction of proteinuria, but complete remission of proteinuria was rare and no data on long-term follow-up evaluation with this drug are available. Good results have been reported with plasmapheresis, immunoadsorption, and lipopheresis. However, all the reports were uncontrolled, small sized, and with short-term follow-up evaluation. In conclusion, there are several therapeutic options for patients who respond to steroids and have further relapses of nephrotic syndrome, but how to treat steroid-resistant patients is still a matter of debate. Nevertheless, a 6-month trial with cytotoxic agents or MMF can be offered to steroid-resistant patients to identify the few patients who respond to these agents. The preliminary results with plasmapheresis or lipopheresis are promising but further studies are needed to assess the role of these treatments.

Topics: Disease Progression; Dose-Response Relationship, Drug; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Mycophenolic Acid; Nephrotic Syndrome; Proteins; Proteinuria

Remission of proteinuria has been shown to be associated with lower rates of kidney disease progression among people with focal segmental glomerulosclerosis (FSGS). The goal of this study was to evaluate whether reductions in proteinuria after treatment are associated with greater kidney survival.. Cohort analysis of clinical trial participants.. Patients with steroid-resistant FSGS enrolled in a randomized treatment trial that compared cyclosporine with mycophenolate mofetil plus dexamethasone.. Reduction in proteinuria measured during 26 weeks after initiating treatment.. Repeated assessments of estimated glomerular filtration rate (eGFR) and time to a composite outcome of kidney failure or death assessed between 26 weeks and 54 months after randomization.. Multivariable linear mixed-effects models with participant-specific slope and intercept to estimate the association of change in proteinuria over 26 weeks while receiving treatment with the subsequent slope of change in eGFR. Multivariable time-varying Cox proportional hazards models were used to estimate the association of changes in proteinuria with time to the composite outcome.. 138 of 192 trial participants were included. Changes in proteinuria over 26 weeks were significantly related to eGFR slope. A 1-unit reduction in log-transformed urinary protein-creatinine ratio was associated with a 3.90mL/min/1.73m. Limited to individuals with steroid-resistant FSGS followed up for a maximum of 5 years.. These findings provide evidence for the benefit of urinary protein reduction in FSGS. Reductions in proteinuria warrant further evaluation as a potential surrogate for preservation of kidney function that may inform the design of future clinical trials.

Topics: Adolescent; Child; Cohort Studies; Creatinine; Cyclosporine; Dexamethasone; Disease Progression; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Mortality; Mycophenolic Acid; Prognosis; Proportional Hazards Models; Proteinuria; Remission Induction; Tissue Survival; Treatment Outcome; Young Adult

Topics: Adult; Arterioles; Blood Pressure; Cyclosporine; Diarrhea; Drug Resistance; Drug Therapy, Combination; Eye Diseases, Hereditary; Female; Fibrosis; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Hyalin; Immunosuppressive Agents; Intestinal Diseases; Male; Mycophenolic Acid; Prednisolone; Prospective Studies; Proteinuria; Skin Abnormalities; Treatment Outcome; Vascular Diseases

Genetic variants in apolipoprotein L1 (APOL1) confer risk for kidney disease. We sought to better define the phenotype of APOL1-associated nephropathy. The FSGS Clinical Trial involved 138 children and young adults who were randomized to cyclosporin or mycophenolate mofetil plus pulse oral dexamethasone with a primary outcome of proteinuria remission. DNA was available from 94 subjects who were genotyped for APOL1 renal risk variants, with two risk alleles comprising the risk genotype. Two APOL1 risk alleles were present in 27 subjects, of whom four subjects did not self-identify as African American, and 23 of 32 (72%) self-identified African Americans. Individuals with the APOL1 risk genotype tended to present at an older age and had significantly lower baseline eGFR, more segmental glomerulosclerosis and total glomerulosclerosis, and more tubular atrophy/interstitial fibrosis. There were differences in renal histology, particularly more collapsing variants in those with the risk genotype (P=0.02), although this association was confounded by age. APOL1 risk genotype did not affect response to either treatment regimen. Individuals with the risk genotype were more likely to progress to ESRD (P<0.01). In conclusion, APOL1 risk genotypes are common in African-American subjects with primary FSGS and may also be present in individuals who do not self-identify as African American. APOL1 risk status is associated with lower kidney function, more glomerulosclerosis and interstitial fibrosis, and greater propensity to progress to ESRD. The APOL1 risk genotype did not influence proteinuria responses to cyclosporin or mycophenolate mofetil/dexamethasone.

Topics: Adolescent; Adult; Apolipoprotein L1; Apolipoproteins; Child; Cyclosporins; Dexamethasone; Female; Follow-Up Studies; Gene Expression Regulation; Genotype; Glomerulosclerosis, Focal Segmental; Humans; Kidney Function Tests; Lipoproteins, HDL; Male; Mycophenolic Acid; Prospective Studies; Risk Assessment; Severity of Illness Index; Survival Rate; Treatment Outcome; Young Adult

Adiponectin is an adipokine that is elevated in kidney disease. Evidence suggests that adiponectin exerts a direct effect on the podocyte and may play a role in the pathogenesis of proteinuria. The objectives of this study were to characterize serum and urine adiponectin levels over time in patients with focal segmental glomerulosclerosis (FSGS) and to evaluate the role of baseline levels of adiponectin as a predictor of clinical remission.. This was a study of 60 individuals, ages 3-38 years, with steroid-resistant FSGS enrolled in the FSGS clinical trial. Serial measurements of serum and urine adiponectin were obtained at baseline and 26 and 52 weeks.. Participants were of mean age 19.4 ± 10.2 years (50% male, 33% black). Serum adiponectin (baseline mean 14.3 ± 6.6 μg/ml) and urine adiponectin:creatinine (Uadp/cr) (baseline mean 126.8 ± 178.9 μg/ml) directly correlated with proteinuria at all time points (r = 0.37-0.81; all p < 0.05). Proteinuria, hypoalbuminemia, and hyperlipidemia were significant independent predictors of greater serum adiponectin and Uadp/cr in multivariate analysis. Lower tertiles of baseline serum adiponectin were associated with greater response to treatment at 52 weeks when adjusted for age, sex, body mass index (BMI) z score, and estimated glomerular filtration rate (eGFR) [odds ratio (OR) 0.48; 95% confidence interval (CI) 0.26-0.91, p = 0.023). For log Uadp/cr, the OR for remission was 0.43 (95% CI 0.21-0.89, p = 0.02) at 52 weeks. However, when baseline urine protein:creatinine was added to the models, the relationships were no longer significant.. Serum and urine adiponectin levels were directly associated with proteinuria and paralleled changes in proteinuria over time in children and young adults with FSGS. Although baseline adiponectin was lower in responders, response to treatment in patients with FSGS was not associated with serum and urine adiponectin levels but, rather, was related to proteinuria.

Topics: Adiponectin; Adolescent; Adult; Anti-Inflammatory Agents; Biomarkers; Child; Child, Preschool; Cyclosporine; Dexamethasone; Enzyme-Linked Immunosorbent Assay; Female; Glomerulosclerosis, Focal Segmental; Humans; Male; Mycophenolic Acid; Treatment Outcome; Young Adult

Drug resistant idiopathic nephrotic syndrome (DRNS) remains a therapeutic dilemma. In this pilot study, the efficacy of the new fully humanised, anti-CD20 monoclonal antibody ofatumumab was tested in 4 children with persistence of proteinuria for at least 12 months in spite of a full drug approach (including rituximab). We used a low-dose 2-infusion ofatumumab model (300+700 mg/1.73 m(2) 2 weeks apart) using specified premedication. Transient normalisation of proteinuria (persisting for 2 months) was achieved in 1 child while another presented stable remission after 12 months; both had normal renal function. The outcome was not modified in the remaining 2 children presenting an impaired renal function. These results demonstrate that low-dose ofatumumab may induce remittance of proteinuria in children with a long story of DRNS and normal renal function. Further studies are needed to test whether higher doses of ofatumumab can also modify proteinuria in patients with impaired renal function.

Topics: Adolescent; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Cyclosporine; Drug Resistance; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Infusions, Intravenous; Male; Mycophenolic Acid; Nephrotic Syndrome; Pilot Projects; Rituximab; Tacrolimus; Treatment Outcome

In the FSGS Clinical Trial, 22 cyclosporine-treated and 20 mycophenolate/dexamethasone-treated patients experienced a complete or partial remission after 26 weeks, completed 52 weeks of treatment, and were studied through 78 weeks. Herein, changes in the urine protein/creatinine ratio (UP/C) and estimated GFR (eGFR) throughout the entire study period are defined.. The FSGS Clinical Trial, which was conducted from November 2004 to January 2010, enrolled patients aged 2-40 years, with eGFR ≥40 ml/min per 1.73 m(2) and UP/C >1 mg/mg after ≥4 weeks of corticosteroid therapy. Both groups received lisinopril or losartan throughout the study. UP/C and eGFR were measured at 0, 26, 52, and 78 weeks.. The median UP/C in the cyclosporine- and mycophenolate/dexamethasone-responsive patients fell by 89.8% and 82.7% at 52 weeks; the fall was largely sustained at 78 weeks (74.7% and 80.3%, respectively). The mean eGFR fell by 19.4% in the cyclosporine group and rose by 7.0% in the mycophenolate mofetil/dexamethasone group at 52 weeks, but subsequently rose by 16.4% and fell by 2.6%, respectively, in the two groups from 52 to 78 weeks.. In this subset of responding FSGS patients, the improvement in UP/C after cyclosporine or mycophenolate/dexamethasone treatment was largely sustained for 6 months after therapy. Reduction in eGFR in the cyclosporine group was improved 6 months after cyclosporine was stopped although the levels were lower than baseline in seven patients who entered the study with decreased eGFR.

Topics: Adolescent; Adult; Child; Child, Preschool; Cyclosporine; Dexamethasone; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Function Tests; Male; Mycophenolic Acid; Prospective Studies; Proteinuria; Young Adult

Optimal therapy of patients with steroid-resistant primary focal segmental glomerulosclerosis (FSGS) remains controversial. This report describes the initial study design, baseline characteristics, and quality of life of patients enrolled in the FSGS Clinical Trial, a large multicenter randomized study of this glomerulopathy comparing a 12-month regimen of cyclosporine to the combination of mycophenolate mofetil and oral dexamethasone. Patients with age ranging 2-40 years, with an estimated glomerular filtration rate > 40 ml/min per 1.73 m², a first morning urine protein-to-creatinine ratio over one, and resistant to corticosteroids were eligible. The primary outcome was complete or partial remission of proteinuria over 52 weeks after randomization. In all, 192 patients were screened, of whom 138 were randomized for treatment. Ethnic distributions were 53 black, 78 white, and 7 other. By self- or parent-proxy reporting, 26 of the 138 patients were identified as Hispanic. The baseline glomerular filtration rate was 112.4 (76.5, 180.0) ml/min per 1.73 m², and urine protein was 4.0 (2.1, 5.3) g/g. Overall, the quality of life of the patients with FSGS was lower than healthy controls and similar to that of patients with end-stage renal disease. Thus, the impact of FSGS on quality of life is significant and this measurement should be included in all trials.

Topics: Administration, Oral; Adolescent; Adult; Chi-Square Distribution; Child; Child, Preschool; Dexamethasone; Drug Resistance; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prospective Studies; Proteinuria; Pulse Therapy, Drug; Quality of Life; Regression Analysis; Research Design; Surveys and Questionnaires; Time Factors; Treatment Outcome; United States; Young Adult

Topics: Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Myasthenia Gravis; Mycophenolic Acid; Plasmapheresis; Treatment Outcome

The combination of cyclosporin A (CsA) and mycophenolate mofetil (MMF) has a synergistic immunosuppressive effect and, as a result, it may induce remission of nephrotic syndrome in patients with steroid- and CsA-resistant focal segmental glomerulosclerosis (FSGS).. To analyse the efficacy and safety of the combined CsA and MMF treatment in patients with cyclosporin A-resistant FSGS.. Twenty-seven patients with CsA-resistant FSGS were treated for 12 months with CsA (4mg/kg/day) combined with MMF (2g/day). The overall follow-up was 5 years. The proportion of patients with remission of proteinuria and the evolution of kidney function after 5 years were used to measure the outcome.. At the end of the treatment period, no patients were in complete remission and 4 patients (14.8%) had reduced proteinuria to values <3.5g/day. These patients had significantly lower baseline proteinuria (5.62±2.19 compared to 8.1±2.96g/day, P=.042), significantly lower GFR (-0.08 compared to -0.69±0.38; P=.003) and higher baseline kidney function (99.6±12.9 compared to 85.05±15.5ml/min; P=.003). Sixteen out of the 27 patients (59.2%) had progressive or stage 5 kidney disease at the end of the follow-up period. Adverse gastrointestinal effects were observed in 33.3% of the patients and acute transitory nephrotoxicity in 14.8%. The dosage and/or number of anti-hypertensive drugs had to be increased in 22.2% of patients during the 12 months of treatment.. Twelve months of combined CsA and MMF therapy does not significantly alter the evolution of kidney function in patients with cyclosporin-resistant FSGS, although it may induce partial reductions in proteinuria.

Topics: Cyclosporine; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Pilot Projects; Prospective Studies

This NIH-funded multicenter randomized study of focal segmental glomerulosclerosis (FSGS) treatment compared the efficacy of a 12-month course of cyclosporine to a combination of oral pulse dexamethasone and mycophenolate mofetil in children and adults with steroid-resistant primary FSGS. Of the 192 patients enrolled, 138 were randomized to cyclosporine (72) or to mycophenolate/dexamethasone (66). The primary analysis compared the levels of an ordinal variable measuring remission during the first year. The odds ratio (0.59) for achieving at least a partial remission with mycophenolate/dexamethasone compared to cyclosporine was not significant. Partial or complete remission was achieved in 22 mycophenolate/dexamethasone- and 33 cyclosporine-treated patients at 12 months. The main secondary outcome, preservation of remission for 26 weeks following cessation of treatment, was not significantly different between these two therapies. During the entire 78 weeks of study, 8 patients treated with cyclosporine and 7 with mycophenolate/dexamethasone died or developed kidney failure. Thus, our study did not find a difference in rates of proteinuria remission following 12 months of cyclosporine compared to mycophenolate/dexamethasone in patients with steroid-resistant FSGS. However, the small sample size might have prevented detection of a moderate treatment effect.

Topics: Adolescent; Adult; Blood Pressure; Child; Child, Preschool; Cyclosporine; Dexamethasone; Drug Therapy, Combination; Female; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Male; Mycophenolic Acid; Prospective Studies; Young Adult

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

The management of patients with steroid-dependent nephrotic syndrome (SDNS) refractory to treatment with long-term steroids, levamisole and cyclophosphamide is difficult. We report our experience on long-term treatment with mycophenolate mofetil (MMF) and alternate-day prednisolone in 42 patients with SDNS previously treated with levamisole (n = 35) and/or cyclophosphamide (n = 37). The mean age (range) at onset of nephrotic syndrome was 37 (13-92) months and at treatment with MMF 104.7 (32-187) months. MMF was administered at a mean daily dose of 26.5 (16.6-31.3) mg/kg for 14.3 (6-45) months. The mean 6-monthly relapse rates decreased from 3.0 episodes before therapy to 0.9 episodes in the first 6 months, 0.7 in next 6 months, and 0.3 in those treated longer than 12 months (P < 0.0001). While on therapy, 32 (76.2%) patients showed 50% or more reduction in relapse rates, and nine (21.4%) had sustained remission. The cumulative dose of prednisolone declined significantly from 0.6 mg/kg per day before to 0.3 mg/kg per day while receiving MMF. Prednisolone requirement was reduced by 50% or more in 16 patients and between 40% and 50% in eight patients. Treatment continuation beyond 12 months resulted in sustained steroid sparing and reduced need for alternative treatments while maintaining low relapse rates. No patients had diarrhea, hematological abnormalities, or impaired renal function. This data confirms the efficacy and safety of treatment with MMF and tapering doses of alternate-day prednisolone in patients with SDNS and supports its use for longer than 12 months.

Topics: Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental; Humans; Male; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Prospective Studies; Remission Induction; Secondary Prevention; Treatment Outcome

Long-term treatment with cyclosporin A (CyA) of children with frequently relapsing steroid-sensitive nephrotic syndrome (SSNS) carries the risk of nephrotoxicity. We have analyzed renal function in 23 children with SSNS during CyA therapy. Repeated measurements of glomerular filtration rate (single-shot 51Cr-EDTA clearance) showed a decline from 131 +/- 21 ml/min per 1.73 m2 to 116 +/- 27 ml/min per 1.73 m2 at last follow-up. Similarly, effective renal plasma flow (simultaneous 123 I-hippurate clearance) was correlated with duration of CyA treatment, and showed a decline from 980 +/- 318 ml/min per 1.73 m2 to 724 +/- 242 ml/min per 1.73 m2. In a pilot study we investigated the effect of mycophenolate mofetil (MMF) in 7 children with a median age of 12.7 years [6 with minimal change nephrotic syndrome (MCNS), 1 with focal segmental glomerulosclerosis (FSGS)] with signs of nephrotoxicity because of long-term CyA therapy. Only 1 patient with SSNS showed a relapse during MMF therapy. In the patient with FSGS, MMF was started in addition to CyA, resulting in complete remission for a follow-up of 28 months. This preliminary study demonstrates that children with MCNS treated with CyA may be successfully converted to MMF without major side effects. In all cases, including FSGS, MMF had a beneficial effect on renal function. These data should be confirmed by a prospective randomized clinical trial.

Topics: Adolescent; Child; Cyclosporine; Drug Therapy, Combination; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrotic Syndrome; Recurrence; Treatment Outcome

Steroid-resistant nephrotic syndrome of childhood poses a dilemma in attempting to balance toxicity of medications against long-term prognosis. This report presents our preliminary experience with the novel use of combined mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the treatment of nine children and young adults with focal glomerulosclerosis (FSGS). All patients were steroid resistant and had failed conventional treatment regimens. Prior to the initiation of the MMF-AB protocol, the patients were pre-treated with weekly intravenous methylprednisolone (MP) (15 mg/kg per week) for 4-8 weeks. Angiotensin-converting-enzyme inhibitors and/or angiotensin receptor blockers were begun when intravascular volume was restored. MMF was given at a dose of 250-500 mg/m(2) per day. Proteinuria, as measured by urine protein/creatinine ratios (Up/c), decreased by 43% following MP ( P<0.05). After 6 months of MMF-AB protocol, the Up/c was 72% below baseline ( P<0.01). This level was maintained for a minimum of 24 months of observation. Similarly, hyperlipidemia, as measured by total cholesterol and triglycerides, improved significantly with treatment (536+/-163 to 265+/-70 mg/dl, 447+/-168 to 230+/-92 mg/dl, respectively, P<0.01). Our data support the use of MMF and AB for treatment of steroid-resistant FSGS when other conventional treatments have failed and/or induced toxicity.

Topics: Adolescent; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Child; Child, Preschool; Drug Resistance; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Male; Methylprednisolone; Mycophenolic Acid; Nephrotic Syndrome; Pilot Projects; Prednisone

A proportion of patients with steroid-dependent nephrotic syndrome (SDNS) experience frequent relapses despite long-term treatment with steroids, levamisole, or/and cyclophosphamide. We prospectively examined the efficacy of long-term therapy with mycophenolate mofetil (MMF) as a steroid-sparing agent in this group.. Nineteen patients with a mean age of 99.1 months (95% confidence interval [CI], 85.3 to 113) who had previously undergone long-term therapy with prednisolone (n = 19), levamisole (n = 16), and cyclophosphamide (n = 15), but had continued to show steroid dependence over many years, were studied. Renal biopsy showed minimal change disease and focal segmental glomerulosclerosis in 10 and 3 patients, respectively. Patients were administered MMF at a mean dose of 29 mg/kg/d (95% CI, 27.4 to 30.7) in 2 divided doses and decreasing doses of alternate-day prednisolone for a mean of 11.8 months (95% CI, 11.4 to 12.2). Relapses were treated with daily prednisolone until remission, with tapering later. They were additionally followed up for a mean of 17 months (95% CI, 15.9 to 18.1).. Mean relapse rates decreased from 6.6 (95% CI, 5.4 to 7.7) to 2 episodes/y (95% CI, 1.2 to 2.7) during MMF treatment (P < 0.0001). Four patients each had 0, 1, 2, and 3 relapses; failure of MMF therapy (>3 relapses during treatment) was seen in 3 patients. Treatment with MMF resulted in steroid sparing, with a reduction in mean prednisolone dose from 0.7 (95% CI, 0.6 to 0.8) to 0.3 mg/kg/d (95% CI, 0.2 to 0.4; P < 0.0001). Fourteen patients showed a 50% or greater reduction in relapse rates; prednisolone therapy could be discontinued for 6 or more months in 8 patients. No significant gastrointestinal or hematologic side effects of MMF treatment were noted. After discontinuation of MMF treatment, 68.4% of patients had an increased frequency of relapses and recurrence of steroid dependence, requiring treatment with other medications.. Long-term therapy with MMF results in significant steroid sparing and reduction in relapse rates in patients with SDNS. Therapy with MMF and tapering doses of prednisolone appears to be a promising intervention in children with SDNS.

Topics: Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Drug Resistance; Drug Therapy, Combination; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Infant; Levamisole; Male; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Prospective Studies; Recurrence; Remission Induction; Safety; 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

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

Topics: Biopsy; Enzyme Inhibitors; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Kidney; Mycophenolic Acid; Nephrotic Syndrome; Treatment Outcome

A 39-year man with primary steroid resistant focal segmental glomerulosclerosis (FSGS) was treated with mycophenolate mofetil and ACE-inhibitors. After six months a different therapeutics approach was mandatory due to the worsening of renal function and the relapse of proteinuria at the nephrotic range. The combination of cascade plasmafiltration and single dose of rituximab (375 mg/m²) achieved clinical remission and improved renal function in six months follow up. Cascade plasmafiltration in association with rituximab can be considered as a salvage method for primary steroid-resistant FSGS. Clinical trials should be carried out for protocol approval.

Topics: Adrenal Cortex Hormones; Adult; Angiotensin-Converting Enzyme Inhibitors; Atorvastatin; Combined Modality Therapy; Diuretics; Drug Resistance; Drug Therapy, Combination; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Plasmapheresis; Platelet Aggregation Inhibitors; Rituximab; Salvage Therapy

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

Background Focal segmental glomerulosclerosis (FSGS) represents 20% of nephrotic syndrome in children. The clinical course and prognosis is heterogeneous in children. The aim of this study was to analyze treatment and outcome of children with FSGS. Methods This retrospective study was conducted in the Department of Pediatrics in Charles Nicolle Hospital during a 15-year period (1996-2010). Results There were 30 children, 16 boys and 14 girls. The mean age was 7 ± 4 years. Nephrotic syndrome was observed in 26 patients, hematuria was noticed in 2 patients and renal insufficiency was detected in 2 patients at presentation. FSGS, not otherwise specified, was the predominant variant. All patients with nephrotic syndrome were treated with steroids. Only three patients responded to it. Twenty one patients were treated with cisclosporin A and this resulted in a 57% complete remission and a 24% partial response. Cyclophosphamide was administered to 6 patients and engendered a 50% complete remission. Six patients were treated with mycophenolate mophetil and showed no response in all cases. Renal insufficiency has been developed in 12 children. Conclusion Results from this study showed that the majority of children with FSGS achieve a high sustained remission rate with ciclosporine A.

Topics: Adolescent; Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Female; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Infant; Male; Mycophenolic Acid; Nephrotic Syndrome; Prognosis; Remission Induction; Retrospective Studies; Tunisia

Topics: Adolescent; Anuria; Cyclosporine; Female; Glomerulosclerosis, Focal Segmental; Graft Rejection; Humans; Immunosorbent Techniques; Immunosuppressive Agents; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Mycophenolic Acid; Plasmapheresis; Postoperative Complications; Prednisolone; Recurrence; Renal Dialysis

Topics: Adult; Cyclosporine; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunologic Factors; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Nephrotic Syndrome; Proteinuria; Receptors, Urokinase Plasminogen Activator; Recurrence; Rituximab; Tacrolimus

Topics: Adaptive Clinical Trials as Topic; Adult; Child; Clinical Trials as Topic; Cyclosporine; Disease Progression; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Mycophenolic Acid; Nephrotic Syndrome; Patient Reported Outcome Measures; Proteinuria; Research Design

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

Topics: Apolipoproteins; Cyclosporins; Dexamethasone; Female; Glomerulosclerosis, Focal Segmental; Humans; Lipoproteins, HDL; Male; Mycophenolic Acid

Topics: Antihypertensive Agents; Cyclophosphamide; Cyclosporine; Drug Substitution; Drug Therapy, Combination; Fatigue; Glomerulosclerosis, Focal Segmental; Gynecomastia; Humans; Hypertension; Male; Mastodynia; Middle Aged; Muscle Weakness; Mycophenolic Acid; Prednisone; Proteinuria; Tacrolimus

There is currently no established standard for maintenance therapy of steroid-resistant nephrotic syndrome (SRNS). We report the long-term clinical course, medication, pharmacokinetic data, and renal function of 23 children with primary, non-familial SRNS with focal segmental glomerulosclerosis (FSGS).. To achieve initial remission, patients were treated with high-dose intravenous (i. v.) methylprednisolone and oral cyclosporin A (CsA). Maintenance therapy included transient alternate day oral prednisolone, CsA and angiotensin-converting enzyme (ACE) inhibitors and/or angiotensin receptor blockers. In 18 patients, mycophenolate mofetil (MMF) (adjusted to achieve blood mycophenolic acid trough concentrations > 2 μg/mL) was sequentially added, and 16 patients were converted to MMF monotherapy.. During a mean follow-up time of 7.0 years (1.7-16.5 years; cumulative observation time 161 patient-years), sustained remission could be achieved in all patients. Five of 23 patients (21%) experienced 10 relapses; all responded to relapse therapy. Maintenance therapy could be permanently discontinued in seven patients (30%). After conversion from CsA to MMF, renal function improved significantly; the eGFR at last follow-up was 137 (range 106-198) mL/min × 1.73 m(2). The mean number of anti-hypertensive drugs decreased from 1.86 per patient after initial remission to 0.57 on MMF monotherapy (P < 0.002).. The data of this uncontrolled retrospective study indicate that in children with SRNS/FSGS achieving initial remission, a sequential steroid-free therapy consisting of a combination of CsA and MMF followed by MMF alone (with the addition of ACE inhibitors and angiotensin receptor blockers), can provide sustained long-term remission, preservation of renal function and better control of blood pressure.

Topics: Administration, Oral; Adolescent; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Child; Child, Preschool; Comorbidity; Cyclosporine; Drug Administration Schedule; Drug Resistance; Female; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Infant; Injections, Intravenous; Male; Mycophenolic Acid; Nephrotic Syndrome; Prednisolone; Remission Induction; Retrospective Studies; Steroids; Treatment Outcome

Given the reported efficacy of mycophenolate mofetil (MMF) in the treatment of glomerular diseases, we question whether MMF can reduce the rate of renal allograft loss due to glomerular disease recurrence compared to azathioprine (AZA) as adjunctive therapy to cyclosporine (CSA)-based immunosuppression.. This is a retrospective study based on the Organ Procurement and Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) database designed to compare the Kaplan-Meier rates of graft loss due to disease recurrence stratified by primary renal diagnoses between recipients receiving CSA+AZA versus CSA+MMF. Recipients of primary kidney transplants (both deceased donor and living, related and unrelated) renal transplants performed between 1 January 1988 and 31 December 2007 with the primary renal diagnosis of IgA nephropathy (IgAN), membranous glomerulonephropathy (MGN), membranoproliferative glomerulonephropathy (MPGN), lupus nephritis (LN) or focal segmental glomerulosclerosis (FSGS) with a functioning allograft at discharge were included.. Seven thousand eight hundred and twenty-six recipients of primary deceased donor kidney transplants (DDKT) [CSA + AZA: IgAN (890), MGN (380), MPGN (193), LN (1324), FSGS (1314) and CSA+MMF: IgAN (855), MGN (614), MPGN (116), LN (715), FSGS (1425)] and 5498 recipients of living donor kidney transplants (LDKT) [CSA+AZA: IgAN (694), MGN (229), MPGN (100), LN (592), FSGS (654) and CSA+MMF: IgAN (1066), MGN (435), MPGN (89), LN (530), FSGS (1109)] were included in the analysis. At 10-year follow-up (mean duration was 5.6 to 6.7±1.8 years in DDKT and 6.2 to 7.4±1.7 years in LDKT), mean times of transplantation (era of transplantation) were: 1992±1.6 years and 2002±1.9 years for the CSA+AZA and CSA+MMF groups, respectively. There was no statistically significant difference in the Kaplan-Meier rates of graft loss due to disease recurrence of any glomerular disease studied between the CSA+AZA and CSA+MMF groups in either DDKT or LDKT recipients. Chi-square analysis revealed no statistically significant difference between the two immunosuppressive regimen groups in terms of age, gender and ethnic background.. The OPTN/UNOS database revealed no difference in the rates of renal allograft loss due to disease recurrence of IgAN, MGN, MPGN, LN and FSGS among recipients receiving either CSA+AZA or CSA+MMF maintenance immunosuppressive therapy at 10-year follow-up.

Topics: Adolescent; Adult; Aged; Azathioprine; Cyclosporine; Female; Follow-Up Studies; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Prognosis; Renal Insufficiency, Chronic; Retrospective Studies; Secondary Prevention; Survival Rate; Tissue Donors; Young Adult

Some evidence suggest an increase in the prevalence of focal segmental glomerular sclerosis (FSGS) in children. To date, there has been no study of the outcome in children with FSGS and its frequency over several decades in Iran. We aimed to report the changing trend of FSGS incidence and its outcome in a sample of Iranian children.. Between 1982 and 2008, all 716 kidney biopsies performed in children referred to Ali Asghar Children Hospital were recorded and confirmed cases with FSGS lesions were further evaluated. Baseline and clinical characteristics of all FSGS patients were assessed and the therapies and outcomes were reviewed.. The incidence rate of FSGS was 10.1% between 1982 and 1990, which was significantly increased to as high as 20.5% after the year 2000 (P = .001). Among 64 children with FSGS, 20 progressed to end-stage renal disease with a mean survival time of 11.45 years (standard error of mean, 1.34 years). Kidney survival rates were 90.4%, 69%, and 47% at 1, 5 and 10 years of follow-up.. Our study demonstrates an increasing trend in FSGS incidence in Iranian children. However, kidney survival rates of our patients were similar to those reported by others in different countries.

Topics: Child; Child, Preschool; Cyclophosphamide; Cyclosporine; Disease Progression; Female; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Incidence; Iran; Kaplan-Meier Estimate; Kidney Failure, Chronic; Male; Mycophenolic Acid; Nephrotic Syndrome; Prevalence; Proportional Hazards Models; Steroids; Treatment Outcome

Overexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to primary FSGS, and one recent study demonstrated elevated levels of serum suPAR in patients with the disease. Here, we analyzed circulating suPAR levels in two cohorts of children and adults with biopsy-proven primary FSGS: 70 patients from the North America-based FSGS clinical trial (CT) and 94 patients from PodoNet, the Europe-based consortium studying steroid-resistant nephrotic syndrome. Circulating suPAR levels were elevated in 84.3% and 55.3% of patients with FSGS patients in the CT and PodoNet cohorts, respectively, compared with 6% of controls (P<0.0001); inflammation did not account for this difference. Multiple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male sex, and treatment with mycophenolate mofetil. In the CT cohort, there was a positive association between the relative reduction of suPAR after 26 weeks of treatment and reduction of proteinuria, with higher odds for complete remission (P=0.04). In the PodoNet cohort, patients with an NPHS2 mutation had higher suPAR levels than those without a mutation. In conclusion, suPAR levels are elevated in geographically and ethnically diverse patients with FSGS and do not reflect a nonspecific proinflammatory milieu. The associations between a change in circulating suPAR with different therapeutic regimens and with remission support the role of suPAR in the pathogenesis of FSGS.

Topics: Adolescent; C-Reactive Protein; Child; Child, Preschool; Cohort Studies; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Randomized Controlled Trials as Topic; Receptors, Urokinase Plasminogen Activator; Young Adult

Topics: Child; Child, Preschool; Cyclosporine; Drug Resistance; Drug Therapy, Combination; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisolone; Tacrolimus; Treatment Outcome

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

Three children under the age of 3 years presented with malignant hypertension, proteinuria, and acute kidney injury. Takayasu's arteritis was diagnosed on the basis of clinical symptoms of weight loss and low grade fever in conjunction with elevated sedimentation rate and radiographic evidence of aortic and renal artery stenosis. One patient had a renal biopsy which showed arteriolar sclerosis and focal glomerulosclerosis. All three patients required multiple antihypertensive agents, ultimately including angiotensin receptor blockers and/or angiotensin converting enzyme inhibitors. The vasculitis was treated with pulse corticosteroids followed by cyclophosphamide in one patient and mycophenolate mofetil as maintenance therapy in all. Follow-up has ranged from 2 to 8 years. Although global renal function has normalized in each patient, two have unilateral non-function of one kidney. The last patient has persistent aortic and renal artery stenosis with complex collateralization requiring ongoing medical and anticipated surgical management.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biopsy; Child, Preschool; Female; Follow-Up Studies; Glomerulosclerosis, Focal Segmental; Humans; Hypertension, Malignant; Immunosuppressive Agents; Infant; Kidney; Male; Mycophenolic Acid; Renal Artery Obstruction; Takayasu Arteritis; Time Factors; Treatment Outcome

In general, anti-HLA antibody belongs to the IgG subclass, but there are very few reports of detection of anti-HLA IgM antibodies. In the present study, we report a renal transplant recipient with a positive NIH-complement dependent cytotoxicity (NIH-CDC) test. The patient was a 24-year-old male with focal segmental glomerulosclerosis (FSGS) as the underlying kidney disease. He had been on maintenance hemodialysis since December 2003 and finally received a living-donor allograft from his mother in October 2008. Pre-transplantation, the NIH-CDC test was positive for both B and T cells, but the flow-cytometric crossmatch test (FCXM) was negative for both cells. The result of the panel-reactive antibody assay (PRA)-single beads test using anti-IgM antibody as the second antibody demonstrated that the positive NIH-CDC test was due to the presence of anti-HLA IgM antibody against the donor-specific antigen A24. Biopsy specimens showed thrombus formation in a small number of glomeruli immediately after the transplantation, but this finding was no longer seen at three months postoperatively. We report successful renal transplantation in a case with anti-HLA IgM antibody.

Topics: Adult; Female; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Graft Rejection; Histocompatibility Testing; HLA-A Antigens; HLA-A24 Antigen; Humans; Immunoglobulin M; Immunosuppressive Agents; Kidney; Kidney Transplantation; Living Donors; Male; Methylprednisolone; Mycophenolic Acid; Tacrolimus

Many children with a late steroid-resistant nephrotic syndrome (SRNS) and focal glomerulosclerosis have a poor prognosis and enter end-stage renal failure (ESRF) within five years. Reports are scarce on the long-term follow-up of patients entering remission while receiving immunosuppressive therapy after steroids have failed. A two-year-old boy with focal and segmental glomerulosclerosis having both late steroid and cyclophosphamide resistance entered complete remission of the SRNS almost two years after starting induction therapy with cyclosporine A (CSA). During the 15-year follow-up, the patient experienced five relapses during CSA maintenance therapy. All relapses were successfully treated within 10 days by intravenous methylprednisolone pulses in addition to CSA. The relapses were accompanied by a drop in the glomerular filtration rate (GFR). At the age of 18 years, the patient had grade II chronic kidney disease (GFR=61 ml/min/1.73 m2). At the age of 14 years, mycophenolate mofetil (MMF) was added to the maintenance therapy and the CSA dosage was reduced. Two renal biopsies at the ages of 10 and 18 years failed to detect CSA nephrotoxicity. We conclude that children with SRNS may have long-term benefit from a combination therapy using intravenous methylprednisolone pulses and CSA.

Topics: Adolescent; Cyclophosphamide; Cyclosporine; Drug Resistance; Glomerular Filtration Rate; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney; Male; Methylprednisolone; Mycophenolic Acid; Nephrotic Syndrome; Remission Induction; Steroids; Time Factors; Treatment Outcome

A case of a young adult with refractory nephrotic syndrome due to focal segmental glomerulosclerosis is reported. Several treatments had been used without success including steroids, cyclophosphamide, cyclosporine A, tacrolimus, and mycophenolate mofetil. Immunoadsorption was performed as a last resort to manage the nephrotic syndrome, which led to a drastic urinary protein reduction. We review the literature supporting immunoadsorption in primary focal segmental glomerulosclerosis.

Topics: Adult; Anemia, Megaloblastic; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Azathioprine; Blood Proteins; Combined Modality Therapy; Cyclophosphamide; Drug Resistance; Glomerulosclerosis, Focal Segmental; Humans; Immunosorbent Techniques; Immunosuppressive Agents; Male; Mycophenolic Acid; Nephrotic Syndrome; Plasmapheresis; Proteinuria; Sepharose; Staphylococcal Protein A; Tacrolimus

Recurrence of focal glomerulosclerosis (FSGS) following renal transplantation is a common cause of allograft loss and clinical morbidity. Recent attempts to control proteinuria and morbidity with plasmapheresis (PP) have met with limited success. Our experience with the use of mycophenolate mofetil (MMF) and angiotensin blockade (AB) in the management of refractory FSGS pre transplant suggested its potential benefit in post-transplant recurrence. This report presents our 25-year experience in pediatric renal transplantation of patients with FSGS divided into two treatment eras: Era 1-prior to use of daclizumab (anti-IL-2R) and Era 2-after daclizumab. A total of 179 pediatric patients were transplanted during the 25-year period. FSGS was confirmed in 27 (15%); 16 of 28 allografts (57%) had recurrence of FSGS during the post-transplant period. In Era 1, only 6 of 16 (38%) recurred in the allograft, while 10 of 12 (83%) recurred during Era 2. The odds ratio of recurrence of FSGS in the allograft after induction with anti-IL-2R was 8.3 (95% confidence interval=1.3-52, P =0.02). Only 2 patients in Era 1 received PP, while 10 in Era 2 were entered into an intensive PP protocol followed by maintenance with AB consisting of angiotensin receptor blockers alone, or in combination with angiotensin-converting enzyme inhibitor. Although proteinuria decreased an average of 80+/-16% with PP, the response was variable and severe morbid edema persisted in poor responders. Maximum benefit occurred with the addition of AB and MMF. After a follow-up of 27+/-15 months, proteinuria has shown a sustained decrease of 94+/-8% below baseline. In conclusion, our experience suggests that, with recurrent FSGS, a limited course of PP followed by maintenance therapy with AB and MMF improves symptoms and may preserve allograft function.

Topics: Adolescent; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Child; Child, Preschool; Daclizumab; Female; Florida; Glomerulosclerosis, Focal Segmental; Graft Survival; Humans; Immunoglobulin G; Immunosuppressive Agents; Infant; Kidney Transplantation; Male; Mycophenolic Acid; Plasmapheresis; Recurrence; Treatment Outcome

Tubulointerstitial inflammation and fibrosis are hallmarks of chronic progressive renal diseases. To characterize the functional interaction between cell infiltration and matrix expansion, this study compared the immunosuppressant mycophenolate mofetil (MMF), intended as primarily anti-inflammatory intervention, the angiotensin-converting enzyme inhibitor enalapril, intended as primarily an anti-fibrotic drug, and a combination of both as anticipated anti-inflammatory/anti-fibrotic intervention. The model used was anti-thy1-induced chronic-progressive glomerulosclerosis (cGS) in the rat, where a brief anti-thy1-induced glomerular injury progresses spontaneously toward tubulointerstitial fibrosis and renal insufficiency. cGS was induced by injection of anti-thy1 antibody into uninephrectomized Wistar rats. One week after disease induction, animals were randomly assigned to the following groups: cGS, cGS plus MMF (20 mg.kg body wt(-1).day(-1)), cGS plus high-dose enalapril (12 mg.kg body wt(-1).day(-1)), and cGS plus both. At week 16 after disease induction, MMF or enalapril alone reduced signs of chronic renal disease significantly and similarly compared with the untreated cGS group. Variables measured included proteinuria, blood pressure, tubulointerstitial and glomerular matrix accumulation, expression of transforming growth factor-beta(1), fibronectin, and plasminogen activator inhibitor-1, infiltration of lymphocytes and macrophages, plasma creatinine and urea levels, and glomerular filtration rate. Combined MMF and enalapril treatment was not superior to single therapy. In conclusion, MMF slows the progression of chronic renal fibrosis and renal insufficiency as effectively as high-dose enalapril in the anti-thy1-induced chronic-progressive glomerulosclerosis model. The dual anti-inflammatory/anti-fibrotic intervention does not yield additive renoprotective effects, indicating that MMF and enalapril interfere with similar or very closely related pathways involved in progression of renal disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Cell Count; Blood Pressure; Body Weight; Disease Progression; Drug Interactions; Eating; Enalapril; Fibronectins; Fibrosis; Glomerulosclerosis, Focal Segmental; Immunohistochemistry; Immunosuppressive Agents; Kidney Diseases; Kidney Function Tests; Male; Mycophenolic Acid; Nephrectomy; Plasminogen Activator Inhibitor 1; Proteinuria; Rats; Rats, Wistar; Thy-1 Antigens; Transforming Growth Factor beta; Transforming Growth Factor beta1

Calcineurin inhibitors are one of the most common drugs used for prevention of acute rejection in recipients of renal allografts. New immunosuppressors have reduced the incidence of acute renal allograft rejection. There have been numerous recent attempts to develop alternative patterns of immunosuppressors for prevention of chronic renal allograft failure, and enhancing its survival. We described a patient who developed numerous complications after the initial postransplant period. He was treated with a calcineurin inhibitors-free immunosuppression in order to avoid nephrotoxicity, but had over 30 ng/ml of sirolimus. Renal function was impaired after cyclosponne withdrawal. Sirolimus was used in association with mycofenolate mofetil and prednisone.

Topics: Adult; Calcineurin Inhibitors; Comorbidity; Cyclosporine; Drug Therapy, Combination; Fever; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Diseases; Kidney Transplantation; Male; Mycophenolic Acid; Prednisone; Pyelonephritis; Recurrence; Sirolimus; Ureteral Diseases; Urinary Bladder Fistula; Urinary Fistula

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

Primary focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage renal disease in both children and adults. Our current treatments are suboptimal, and a significant percentage of cases are resistant to current therapy.. We performed an open-label, 6-month trial of the new immunosuppressive agent mycophenolate mofetil (MMF) in 18 biopsy-proven patients resistant to a course of corticosteroids therapy. Seventy-five percent had also failed to respond to a cytotoxic agent and/or a calcineurin inhibitor.. A substantial improvement in proteinuria was seen in 44% (8/18) of the patients by 6 months. This was sustained for up to 1 year post treatment in 50% (4/8) of this group. No patient had a complete remission. No deterioration in renal function was observed in any patient over the treatment period, but 3 progressed to chronic kidney failure during follow-up. Adverse effects were mild. Only 1 patient required a dose reduction due to an intercurrent infection.. MMF appears safe to use in this group of patients and did lower proteinuria in 44% of this cohort resistant to other forms of treatment. Relapses were common, suggesting more prolonged or combination therapy may be required. More rigorous trials utilizing this medication should be considered to further assess the risk-benefit ratio of treatment with MMF in patients with FSGS.

Topics: Adult; Aged; Female; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Failure, Chronic; Male; Middle Aged; Mycophenolic Acid; Treatment Outcome

Mycophenolate mofetil (MMF) is known to attenuate glomerulosclerosis in experimental models of renal failure. We investigated whether this is mediated by reduction of oxidative stress.. Effects of MMF on oxidative stress are studied in an experimental rat model (NA model) involving unilateral nephrectomy and two intravenous injections with adriamycin (2 mg/kg). Rats are sacrificed after 2 and 6 weeks. Glomerulosclerosis and tubulointerstitial lesions are demonstrated by histological techniques. Presence of macrophages/monocytes (ED1) and myofibroblasts (alpha-SMA) is demonstrated by immunohistochemistry. Oxidative stress is evaluated by enzymatic measurements (AOE), spectrofluorometry (TBARS), immunohistochemistry (MDA and HNE) and histology (ferric iron deposition).. The NA model shows proteinuria, hypercholesterolemia, beginning glomerulosclerosis, tubulointerstitial sclerosis and tubular dilatation, glomerular, periglomerular and interstitial presence of alpha-SMA and increased presence of macrophages/monocytes after 6 weeks. Oxidative stress in renal cortex is apparent (increased cortex TBARS concentration, increased glomerular presence of MDA and HNE, decreased activity of antioxidant enzymes, ferric iron deposition in proximal tubules) after 6 weeks. MMF administration results in a decrease of glomerulosclerosis, interstitial sclerosis, glomerular and periglomerular expression of alpha-SMA and the number of ED1-positive cells in tubulointerstitium and glomeruli. Proteinuria and cholesterolemia are not decreased. TBARS level, and activities of catalase, Mn and Cu/Zn superoxide dismutase as well as the presence of ferric iron in the proximal tubules are not changed by MMF treatment. Cortex activity of glutathione peroxidase returns to normal.. MMF has a favorable effect on glomerular and interstitial fibrosis in the NA model of kidney disease, but not on proteinuria and cholesterolemia. Improvement of fibrosis cannot be explained by major changes in oxidative stress or antioxidant defense.

Topics: Actins; Animals; Antibodies, Monoclonal; Antigens; Glomerulosclerosis, Focal Segmental; Kidney; Kidney Cortex; Kidney Glomerulus; Macrophages; Male; Monocytes; Muscle, Smooth, Vascular; Mycophenolic Acid; Oxidative Stress; Rats; Rats, Wistar

Recent studies have suggested that subtle microvascular and tubulointerstitial injury in the kidney can cause salt-sensitive hypertension. To test this hypothesis, we determined whether the mild renal disease induced by transient blockade of nitric oxide (NO) synthesis would result in salt-sensitive hypertension and whether prevention of the renal injury by coadministration of the immunosuppressive agent mycophenolate mofetil (MMF) would block the development of salt sensitivity. N(omega)-nitro-L-arginine-methyl ester (L-NAME; 70 mg/100 ml in the drinking water) was administered for 3 wk to rats with or without MMF (30 mg x kg(-1) x day(-1) by gastric gavage), followed by a 1-wk "washout" period in which the MMF was continued, which was followed in turn by placement on a high-salt (4% NaCl) diet for an additional 4 wk. Renal histology was examined at 3 and 8 wk, and blood pressure was measured serially. L-NAME treatment resulted in acute hypertension and the development of mild renal injury. During the washout period, blood pressure returned to normal, only to return to the hypertensive range on exposure of the animals to a high-salt diet. MMF treatment prevented the development of hypertension in response to a high-salt diet. This correlated with the ability of MMF to inhibit specific aspects of the renal injury, including the development of segmental glomerulosclerosis, the infiltration of T cells and ANG II-positive cells, and the thickening of afferent arterioles.

Topics: Animals; Blood Pressure; Body Weight; Glomerulosclerosis, Focal Segmental; Hypertension; Immunosuppressive Agents; Kidney; Lymphocytes; Macrophages; Male; Mycophenolic Acid; Nephritis, Interstitial; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin

Overexpression of inducible nitric oxide synthase (iNOS) has been implicated in the pathogenesis of lupus glomerulonephritis. Mycophenolate mofetil (MMF), a novel immunosuppressive agent, is currently used in organ transplantation and under evaluation for treatment of autoimmune disorders. Mycophenolic acid, the active metabolite of MMF, has been shown to suppress cytokine-induced nitric oxide production in vitro. The aim of this study was to evaluate the effect of MMF on the expression of renal cortical iNOS mRNA and protection against glomerulonephritis in MRL/lpr mice. Three-month-old MRL/lpr mice (n = 6) displaying clinical symptoms of glomerulonephritis were treated for 3 months with MMF (90 mg/kg/day) dissolved in a vehicle. Controls were age- and sex-matched mice (n = 6) that received the vehicle alone. By reverse-transcription competitive polymerase chain reaction, we found that the renal cortical iNOS/beta-actin mRNA ratio was reduced by 30.8% (P <.05) in MMF-treated mice. Furthermore, MMF significantly reduced urinary nitrite production and degree of glomerulosclerosis. The glomerular volume was reduced by 17.5% (P <.001). Proteinuria was also significantly reduced in the MMF-treated group. However, by electrophoretic mobility shift assay, the nuclear binding of nuclear factor-kappaB (NF-kappaB) was not affected by MMF treatment. We conclude that in addition to its immunosuppressive action, MMF may reduce renal cortical iNOS mRNA expression and diminish glomerulosclerosis in MRL/lpr mice independent of modulation of the NF-kappaB pathway.

Topics: Animals; Cell Count; Creatinine; Enzyme Inhibitors; Female; Gene Expression Regulation, Enzymologic; Glomerulosclerosis, Focal Segmental; Immunohistochemistry; Kidney Glomerulus; Lupus Nephritis; Mice; Mice, Inbred MRL lpr; Mycophenolic Acid; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Proteinuria; RNA, Messenger; Transcriptional Activation

We report an 8-year-old Caucasian boy who presented with steroid-resistant nephrotic syndrome. Renal biopsy showed the cellular variant of focal segmental glomerulosclerosis (FSGS). Within 1 year he received a series of therapies that have induced remission in other patients with this disease, all to no avail (conventional-dose cyclosporin A, methylprednisolone pulse therapy, high-dose cyclosporin A, and therapy with mycophenolate mofetil). He achieved remission after five sessions of plasma exchange. This case argues for aggressive therapy of resistant nephrotic syndrome in the native kidney. Plasma exchange should be considered as a possible rescue therapy arm in future study protocols.

Topics: Child; Cyclosporine; Dose-Response Relationship, Drug; Drug Resistance; Glomerulosclerosis, Focal Segmental; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Mycophenolic Acid; Plasmapheresis; Remission Induction

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