mycophenolic-acid and Retroperitoneal-Fibrosis

Idiopathic retroperitoneal fibrosis (IRF) is a rare condition characterized by the development of a peri-aortic and peri-iliac tissue showing chronic inflammatory infiltrates and pronounced fibrosis. Ureteral entrapment with consequent obstructive uropathy is one of the most common complications of IRF, which can lead to acute renal failure and, in the long term, to varying degrees of chronic kidney disease. IRF may be isolated or develop in association with autoimmune diseases (e.g. Hashimoto's thyroiditis and psoriasis) and other fibro-inflammatory disorders (often within the spectrum of immunoglobulin G4-related disease), which suggests that it should be considered as a potentially systemic condition. IRF is an immune-mediated disease: genetic variants (e.g. human leukocyte antigen (HLA)-DRB1*03) and environmental agents (mainly exposure to asbestos and smoking) are strongly associated with an increased risk of developing the disease, while a complex network of chemokines (e.g. CXCL12 and C-C moti chemokine 11 (CCL11)) and cytokines [e.g. interleukin (IL)-6, IL-12 and IL-13] is likely to orchestrate the inflammatory response and simultaneously promote fibrosis. Glucocorticoids, alone or in combination with traditional immunosuppressants such as methotrexate and mycophenolate mofetil, are usually efficacious and promptly induce disease remission; however, up to 50% of patients relapse, thus requiring repeat immunosuppressive courses. Biologic drugs, namely rituximab, are being explored for the treatment of IRF. In addition to medical therapies, interventional procedures (mainly ureteral stenting) are required to relieve ureteral obstruction, whereas surgical ureterolysis is generally reserved to refractory cases. If appropriately treated, then the overall and renal prognosis of IRF are good, with <5% patients developing end-stage renal disease.

Topics: Chemokines; Cytokines; Glucocorticoids; Humans; Methotrexate; Mycophenolic Acid; Nephrologists; Retroperitoneal Fibrosis; Rituximab; Ureteral Obstruction

To assess the therapeutic benefit of mycophenolate mofetil (MMF) in retroperitoneal fibrosis (RF).. MMF 2 g/day and prednisone 1 mg/kg were initiated in nine patients with radiological (9/9) and histological verification (2/9) of idiopathic RF. Out of nine patients, seven needed bilateral ureteral stenting due to extensive hydronephrosis.. All patients experienced regression of radiological extension. Out of seven patients, five were free of ureteral catheters after a mean of 5.6 months and two remained on stenting due to secondary stenosis. Within 6 months mean creatinine and CRP fell from 2.5 to 1.2 mg/dl and from 4.0 to 1.4 mg/dl, respectively. MMF was discontinued after a mean of 27 months. Prednisone was tapered to zero after a mean of 7 months. Side-effects were urinary tract infections in 7/9 patients and impaired glucose tolerance in 3/9. No recurrence occurred after withdrawal of glucocorticoids and MMF in 7/9 patients after a mean overall follow-up of 55 months (range 12-120).. Treatment with MMF and glucocorticoids was successful in inducing partial or complete and lasting remission in RF. The results suggest the use of MMF as additional immunosuppressive option.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Immunosuppressive Agents; Magnetic Resonance Imaging; Male; Middle Aged; Mycophenolic Acid; Prednisone; Retroperitoneal Fibrosis; Treatment Outcome

Topics: Aged; Anti-Infective Agents; Anti-Inflammatory Agents; Enzyme Inhibitors; Humans; Immunoglobulin G; Male; Mycophenolic Acid; Prednisone; Retroperitoneal Fibrosis

Topics: Decompression, Surgical; Diagnosis, Differential; Drug Administration Schedule; Humans; Immunoglobulin G; Mycophenolic Acid; Nephrostomy, Percutaneous; Prednisone; Retroperitoneal Fibrosis; Tomography, X-Ray Computed; Ureteral Obstruction

Small series and case reports suggest that a combination of mycophenolate mofetil and prednisone is an efficatious and safe treatment for patients with retroperitoneal fibrosis.. To describe the outcomes of patients with retroperitoneal fibrosis treated with a combination of prednisone and mycophenolate mofetil.. Prospective, case series.. 31 patients with retroperitoneal fibrosis.. Single-center tertiary care facility.. Prednisone 40 mg administered daily and tapered over 6 months and mycophenolate mofetil 1,000 mg given twice daily.. Clinical course, laboratory assessment, measurement of periaortic mass.. Systemic symptoms resolved in all patients. Eighty-nine percent of patients had a 25% or greater reduction in periaortic mass. Eighteen patients had 32 obstructed ureters. Thirty of these ureters were free of obstruction after an average of 513 days of therapy. Laboratory abnormalities of elevated erythrocyte sedimentation rate and serum creatinine and decreased hemoglobin levels normalized in all patients. Recurrent disease occurred in 2 of 28 patients.. Combined prednisone and mycophenolate mofetil appears to be an effective therapeutic option for patients with retroperitoneal fibrosis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Aortic Diseases; Disease Management; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mycophenolic Acid; Prednisone; Prospective Studies; Retroperitoneal Fibrosis; Retrospective Studies; Tertiary Care Centers; Treatment Outcome; Ureteral Obstruction

Small case series suggest that a combination of mycophenolate mofetil and prednisone may be an effective treatment for patients with retroperitoneal fibrosis.. To describe the outcomes of adults with retroperitoneal fibrosis who received a combination of prednisone and mycophenolate mofetil.. Prospective case series of patients followed between 1 April 2005 and 1 July 2009.. Single tertiary care facility.. 28 patients with retroperitoneal fibrosis.. Prednisone, 40 mg/d, tapered over 6 months, and mycophenolate mofetil, 1000 mg twice daily, for a mean of 24.3 months.. Clinical course, laboratory assessment, and measurement of periaortic mass. Mean follow-up was 1012 days, and no patients were lost to follow-up.. Systemic symptoms resolved in all patients; 89% had a 25% or greater reduction in periaortic mass. Elevated erythrocyte sedimentation rate and serum creatinine level and decreased hemoglobin level normalized in all patients. Disease recurred in 2 of 28 patients.. This was a small case series.. Combined prednisone and mycophenolate mofetil therapy is a potentially effective treatment for retroperitoneal fibrosis that warrants evaluation in randomized trials.. None.

Topics: Adult; Aged; Anti-Inflammatory Agents; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisone; Prospective Studies; Retroperitoneal Fibrosis; Tomography, X-Ray Computed; Treatment Outcome

The pathogenesis of idiopathic retroperitoneal fibrosis (IRPF) has been attributed to an autoimmune response to atherosclerotic lipid material leaking from blood vessels. Corticosteroids and cytotoxic agents have been used for therapy. Based on the immunosuppressive and anti-fibrotic action of mycophenolate, we administered this agent to a patient with biopsy-proven IRPF and achieved a rapid, complete and sustained remission with a 6-year follow-up.

Topics: Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retroperitoneal Fibrosis

Idiopathic retroperitoneal fibrosis (IRPF) is an unusual progressive illness for which consistent therapeutic recommendations have not been devised. The present report describes a collaborative nephrology and urology approach to distinguish IRPF from secondary disease and then combine necessary acute surgical or radiological intervention with short-term corticosteroid and with mycophenolate mofetil (MM) to facilitate steroid tapering and long-term management.. 21 patients have been evaluated and followed over a 7-year period, 16 with characteristic IRPF and 5 with secondary retroperitoneal disease. IRPF patients initially received high-dose corticosteroid and MM. We report clinical follow-up along with imaging studies of the retroperitoneum and related organs, serologic markers for systemic disease, and nonspecific acute-phase reactants as indicators of ongoing disease activity.. Among IRPF patients, uniform success in stabilizing clinical signs and symptoms, radiological disease in the retroperitoneum and associated organs, and inflammatory indicators have been observed. Corticosteroid therapy can be limited to 6 months or less and MM to approximately 2 years, all with substantial impact on the natural history of IRPF.. This is not a randomized, controlled trial, and patients were often referred with prior complications and/or treatments, however, the systematic approach and consistent results support the utility of MM as a safe and effective choice for long-term stabilization in IRPF.

Topics: Adult; Aged; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Retroperitoneal Fibrosis

Topics: Anti-Inflammatory Agents; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Middle Aged; Mycophenolic Acid; Prednisolone; Retroperitoneal Fibrosis; Tomography, X-Ray Computed

We determined the efficacy of a combination of corticosteroids and mycophenolate mofetil for retroperitoneal fibrosis.. We performed a prospective observational study of the treatment of 7 patients with biopsy proven retroperitoneal fibrosis. Patients were treated with 40 mg prednisone daily with a gradual taper over 6 months. Mycophenolate mofetil was administered at a starting dose of 1,000 mg twice daily and continued for 6 months following resolution of systemic symptoms and extubation of affected ureters. Outcomes included normalization of laboratory evidence of inflammation, regression of fibrosis by computerized tomography and the ability to discontinue ureteral stents.. Seven patients were treated with mycophenolate mofetil and prednisone. Five of the 7 patients had bilateral ureteral obstruction and 1 had unilateral obstruction requiring ureteral stents. Baseline and followup laboratory values were C-reactive protein 8.9 and 1.3 mg/dl (p=0.07), hemoglobin 10.7 and 12.7 gm/dl (p=0.001), erythrocyte sedimentation rate 76 and 14.5 mm per hour (p=0.015) and serum creatinine 3.32 and 1.08 mg/dl (p=0.07), respectively. Six of the 7 patients had a mean 32% regression of the retroperitoneal mass on computerized tomography. Ten of the 11 obstructed ureters were free of obstruction following ureteral stent removal. The mean time to stent removal was 10.5 months. One patient had a distal ureteral stricture and continued to require decompression. There were no treatment related side affects.. Mycophenolate mofetil combined with prednisone was safe and efficacious in this small cohort of patients with retroperitoneal fibrosis. Larger trials are needed to confirm these results.

Topics: Adult; Aged; Constriction, Pathologic; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Mycophenolic Acid; Prednisone; Retroperitoneal Fibrosis; Tomography, X-Ray Computed; Ureter

[corrected] Idiopathic retroperitoneal fibrosis (IRF) is an uncommon disease characterized by a retroperitoneal fibrotic tissue that often involve the ureters, leading to the obstructive nephropathy and variable impairment of renal function. Findings strongly suggest an autoimmune etiology. Surgery, medical treatment with immunosuppressive drugs, or a combination of both are proposed. The optimal treatment has not been established yet. The aim of this study was to present our experience with combined immunosuppressive therapy of IRF, steroids (S) and mycophenolate mofetil (MMF).. We prospectively followed four patients with IRF from January 2004 to December 2006. Three patients had an active disease with bilateral hydronephrosis. In the two of them acute renal failure was presented, and ureteral catheters were inserted in one in order to manage ureteral obstruction. One patient has came to our unit with a relapse of IRF and incipient chronic renal failure after the prior therapy with ureterolysis and immunosuppressive drugs (azathioprine and tamoxifen). All patients received steroids and MMF. Two patients were treated with intravenous methylprednisolone pulses (250 mg each), for three consecutive days, followed by oral prednisone 0.5 mg/kg/day. The other two patients received oral prednisone at the same dose. Prednisone was gradually tappered to a maintenance dose of 10 mg/kg/day. Simultaneously, all patients received MMF, initially 1 g/day with the increase to 2 g/day.. After four weeks of the therapy all symptoms disappeared, as well as a hydronephrosis with a decrease of erythrocyte sedimentation rate and Creactive protein (CRP) to normal level in all patients. Three patents remain in remission untill the end of the follow up. One patient had a relapse because of stopping taking the therapy after six months. He was treated by oral prednisone 0.5 mg/kg/day, which was gradually decreased. After twelve weeks hydronephrosis disappeared and CRP returns to the normal level.. The combination of steroids and mycophenolate mofetil led to the remission of IRF with a strong and quick immunosuppressive effect. It also provided avoiding the long-term use of high steroid dose and surgical procedures.

Topics: Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Methylprednisolone; Middle Aged; Mycophenolic Acid; Prednisone; Retroperitoneal Fibrosis; Ureteral Obstruction

Topics: Adult; Anti-Inflammatory Agents; Humans; Immunosuppressive Agents; Male; Mycophenolic Acid; Prednisone; Retroperitoneal Fibrosis; Tomography, X-Ray Computed; Treatment Outcome