mycophenolic-acid and Anti-Glomerular-Basement-Membrane-Disease

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

This study describes the pharmacokinetics of mycophenolate mofetil (MMF) in 15 pediatric patients with vasculitis and connective tissue disease involving the kidney. Patients included 10 with systemic lupus erythematosus (SLE), 1 with antiphospholipid antibody syndrome, 2 with Wegener granulomatosis, and 1 each with Goodpasture syndrome, Henoch-Schönlein-associated nephritis, and 1 with severe tubulointerstitial nephritis and uveitis. All patients were treated with steroids and additional therapy prior to treatment with MMF, which was administered for a median of 491 days. Mean starting dose of MMF was 974+/-282 mg/m(2 )in two divided doses. Pharmacokinetic monitoring of the active compound of MMF, mycophenolic acid (MPA), was performed using an EMIT assay. The mean MPA AUC after a median of 39 days was 61.8+/-31.0 micro gxh/ml, median time to maximum concentration was 60 min, and mean maximum concentration was 18.5+/-8.4 micro g/ml. At last follow-up, mean MMF dose was 900+/-341 mg/m(2) per day, and mean trough MPA concentration was 3.1+/-1.1 (range 0.6-4.6) micro g/ml. Therapy was effective in inducing remission in 4 of 9 patients with active disease. Only 1 of the 5 other patients relapsed. All 6 patients with controlled disease maintained remission. There were few side effects: one episode each of diarrhea and leukocytopenia and two viral infections. We conclude that MMF at 900 mg/m(2) per day appears to be effective in these patients.

Topics: Adolescent; Anti-Glomerular Basement Membrane Disease; Antiphospholipid Syndrome; Autoimmune Diseases; Child; Female; Granulomatosis with Polyangiitis; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Mycophenolic Acid; Nephritis, Interstitial; Remission Induction; Treatment Outcome

Topics: Acute Kidney Injury; Anti-Glomerular Basement Membrane Disease; Child; Cyclophosphamide; Enzyme Inhibitors; Glucocorticoids; Humans; Immunosuppressive Agents; Kidney; Male; Mycophenolic Acid; Plasmapheresis

An 18-year-old woman presented with anemia, pulmonary hemorrhage, and necrotizing glomerulonephritis, and was diagnosed with anti-glomerular basement membrane (anti-GBM) disease. Treatment was undertaken with plasma exchange, mycophenolate mofetil and corticosteroids, due to patient refusal of cyclophosphamide. Clinical remission was successfully induced with this fertility-sparing regimen. A relapse due to therapy non-adherence was successfully treated with a second course of plasmapheresis, mycophenolate, and steroids. Thereafter, 6 months of directly observed therapy resulted in a favorable outcome with well-preserved pulmonary and renal function. This case suggests the possibility that mycophenolate may have a role in the treatment of anti-GBM disease.

Topics: Adolescent; Adrenal Cortex Hormones; Anti-Glomerular Basement Membrane Disease; Female; Fertility Preservation; Humans; Immunosuppressive Agents; Mycophenolic Acid; Organs at Risk; Plasmapheresis

Glomerular crescent formation is a prominent feature of aggressive forms of glomerulonephritis (GN) and is associated with a poor prognosis. We investigated whether the potent immunosuppressive agent mycophenolate mofetil (MMF) could prevent crescent formation in a model of anti-glomerular basement membrane (GBM) GN in the rat.. GN with glomerular crescents was induced by the injection of anti-GBM antibody to female Wistar-Kyoto (WKY/NCrj) rats. The experimental rats were divided into two groups: rats received vehicle (0.5% carboxymethylcerlose) or MMF (20 mg/kg/day) orally. Body weight was measured and the urine and blood samples were evaluated. The rats were sacrificed at day 14, and histological analysis was performed. The mRNA expression of cytokines and adhesion molecules in the kidney was analysed by reverse transcription-polymerase chain reaction (RT-PCR).. Marked proteinuria, glomerular crescent formation and glomerulosclerosis were observed in this model, and these were significantly reduced by MMF treatment. Marked glomerular macrophage and T-cell infiltration was also observed, and MMF treatment significantly inhibited macrophage but not T-cell infiltration. RT-PCR and immunohistochemical analysis revealed that mRNA and protein expression of osteopontin was decreased by the treatment with MMF. In addition, MMF treatment in the early stages of GN could inhibit proteinuria, glomerular crescent formation and glomerulosclerosis.. These findings suggest therapeutic potential for MMF in the inhibition of glomerular crescent formation in GN and provide new insights into the mechanism underlying the amelioration of crescentic GN by MMF treatment.

Topics: Animals; Anti-Glomerular Basement Membrane Disease; Female; Immunosuppressive Agents; Kidney Glomerulus; Macrophages; Mycophenolic Acid; Osteopontin; Proteinuria; Rats; Rats, Inbred WKY; Sialoglycoproteins; T-Lymphocytes

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Humans; Immunosuppressive Agents; Kidney; Kidney Transplantation; Male; Mycophenolic Acid; Plasma Exchange