Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug whose active metabolite, mycophenolic acid (MPA), blocks the action of inosine monophosphate dehydrogenase, resulting in the inhibition of the novo purine synthesis. Thus, MPA has an antiproliferative effect on T and B lymphocytes and also inhibits the glycosylation of cell surface adhesion proteins involved in cell-cell contact and in the recruitment of circulating leukocytes to sites of tissue damage and inflammation. In this study, the effect of MMF in the mercury model of nephritis was examined. Repeated exposure to HgCl(2) induces an autoreactive Th2 cell subset-inducing polyclonal B cell activation in the Brown Norway (BN) rat. This leads to the development of an autoimmune syndrome characterized by synthesis of autoantibodies (mainly anti-glomerular basement membrane [GBM] Abs) with glomerular linear deposits of IgG, proteinuria, and tubulointerstitial nephritis. Results show that MMF has a preventive effect on mercury-induced disease as it blocks anti-GBM Ab synthesis, thus avoiding glomerular IgG deposits and proteinuria and the development of interstitial nephritis. However, the therapeutic effect of MMF seems to be restricted to its antiinflammatory properties blocking the extravasation of circulating leukocytes to renal interstitium by interfering with the very late activation antigen 4/vascular cell adhesion molecule-1 (VCAM-1) cell adhesion pathway. Also, MMF administration to mercury-injected rats reduces the secretion of the proinflammatory cytokine tumor necrosis factor-alpha. These findings confirm that MMF has a strong effect on the primary immune response in this model. Nevertheless, when the disease is in progress, MMF acts exclusively on the inflammatory response. MMF could be useful in the treatment of diseases associated with renal inflammation.
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PMID:Effects of mycophenolate mofetil in mercury-induced autoimmune nephritis. 1191 53

Mycophenolate mofetil (MMF), the prodrug ofmycophenolic acid (MPA), is a selective, non-competitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) and of the type II isoform in particular. IMPDH is the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides. MMF strongly inhibits both T- and B lymphocyte proliferation and has been used in the prevention of acute and chronic allograft rejection since the mid 1990s. Recent evidence, however, suggests that MMF is also capable of inhibiting the proliferation of non-immune cells. In various cell lines, i.e. smooth muscle cells, renal tubular cells and mesangial cells, MPA reduced or even abrogated proliferation in response to proliferative stimuli. Furthermore, data from our own laboratory demonstrate a dose-dependent inhibition of dermal fibroblast proliferation by MPA. In animal studies, MMF ameliorated renal lesions in immune-mediated disease, i.e. in the anti-thy 1.1 model and experimental lupus nephritis, but was also effective in non-immune-mediated renal damage in the rat remnant-kidney model. These observations prompted several investigators to study the effects of MMF in proliferating (renal) disease of non-immune origin in humans. MMF significantly reduced proteinuria in minimal-change disease and focal segmental glomerulosclerosis. In addition, MMF showed beneficial effects in the treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity through reduction of immune- and non-immune-mediated renal damage. MMF is well tolerated and has proven to be a relatively safe drug causing only minor bone marrow suppression. Taken together, there is a growing body of evidence pointing to therapeutic applications of MMF other than immunosuppression, in particular the prevention of fibrosis.
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PMID:Review of the antiproliferative properties of mycophenolate mofetil in non-immune cells. 1470 52

The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.
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PMID:[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report]. 1689 86

Mycophenolic acid (MPA) is a highly selective, non-competitive and reversible inhibitor of the inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme in the de novo biosynthesis of guanosine nucleotides. Mycophenolate mofetil (MMF, the ester prodrug of MPA) strongly inhibits both T- and B-lymphocyte proliferation and has now been widely used in the prevention of acute and chronic allograft rejection. Recent evidence, however, suggests that MMF is also capable of inhibiting the proliferation of non-immune cells. In various cell lines, e.g. smooth muscle cells, renal tubular cells, mesangial cells, and fibroblasts, MPA reduced or even abrogated proliferation in response to proliferative stimuli. In animal studies, MMF ameliorated renal lesions in immune-mediated disease, e.g. in the Anti-Thy 1.1 model and experimental lupus nephritis, but was also effective in non-immune-mediated renal damage, e.g. in the rat remnant kidney model or in a model of chronic cyclosporine nephrotoxicity in the rat. In humans, MMF reduced proteinuria in steroid-resistant nephrotic syndrome and had beneficial effects in the prevention and treatment of chronic allograft nephropathy and calcineurin inhibitor toxicity through the reduction of immune- and non-immune-mediated renal damage. MMF is well tolerated and has proven to be a relatively safe drug. Taken together, there is a growing body of evidence pointing to therapeutic applications of MMF other than immunosuppression, in particular the prevention of fibrosis.
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PMID:Antifibrotic actions of mycophenolic acid. 1710 Jun 98

Idiopathic nephrotic syndrome (INS) is defined as massive proteinuria and hypoalbuminemia associated with dyslipidemia and generalized oedema in most cases. It is thought to be due to a plasma factor of immunologic origin. Most cases are steroid responsive. However, a considerable proportion of children run a steroid dependent course. Calcineurin inhibitors and alkylating agents have been classical treatment strategies for such cases, but specific toxicity limits the use of these drugs. Mycophenolate mofetil (MMF) is an inhibitor of inosine monophosphate dehydrogenase and thus de novo purine synthesis. Several uncontrolled clinical trials have demonstrated the efficacy of MMF in steroid dependent NS with or without prior use of CyP and in children with nephrotoxicity due to prolonged CyA treatment. Non-compliance to steroid therapy can be responsible for multiple relapses and may be misinterpreted as steroid dependency and may therefore lead to unjustified increase of immunosuppressive treatment. Triamcinolone acetonide, a long acting steroid for intramuscular injection, can replace the usual oral prednisone treatment if non-compliance is suspected. Whereas the treatment of the primary course of INS is well established, steroid dependent and steroid resistant forms are still a challenge for pediatric nephrologists. Both under-treatment with multiple relapses with disease or steroid associated morbidity on the one hand and over-treatment with specific side effects of immunosuppressive drugs may have severe consequences for the patients.
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PMID:Pediatric idiopathic nephrotic syndrome: treatment strategies in steroid dependent and steroid resistant forms. 2015 72

Idiopathic nephrotic syndrome (INS) is probably due to a plasma factor of immunologic origin. This circulating factor probably interacts with the glomerular filtration barrier and is responsible for massive proteinuria. Most patients respond to steroids. However, a considerable proportion of children run a steroid dependent course. Cyclosporine A (CyA) and cyclophosphamide (CyP) have been classical treatment strategies for such cases, but specific toxicity limits the use of these drugs. Mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase and thus de novo purine synthesis. Clinical trials have demonstrated the efficacy of MMF in steroid dependent NS and in children with nephrotoxicity due to prolonged CyA treatment. While MMF is a well established strategy against steroid dependency, rituximab (RTX) has emerged as a new treatment option in case of calcineurin inhibitor dependency. Non-compliance to steroid therapy can be responsible for multiple relapses and may be misinterpreted as steroid dependency and may therefore lead to unjustified increase of the immunosuppressive treatment. Triamcinolone acetonide, a long acting steroid for intramuscular injection, can replace the usual oral prednisone treatment if non-compliance is suspected. Whereas the treatment of the primary course of INS is well established, steroid dependent and steroid resistant forms are still a challenge for pediatric nephrologists. Both under-treatment with multiple relapses with disease or steroid associated morbidity on the one hand and over-treatment with specific side effects of immunosuppressive drugs may have severe consequences for the patients. The narrow path between steroid side effects and potential nephrotoxicity emphasizes the need for individualized management in severe form of INS.
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PMID:New treatment strategies in idiopathic nephrotic syndrome. 2249 88