Clinical Trial: Efficacy of Pentoxifylline on Rapidly Progressive Glomerulonephritis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Clinical Efficacy of Combined Pentoxifylline and Conventional Immunosuppressive Regimens on Patients With Rapidly Progressive Glomerulonephritis

Brief Summary: We have recently demonstrated that pentoxifylline (PTX) has the potential to treat severe glomerular inflammation in a rat model of accelerated anti-glomerular basement membrane (GBM) glomerulonephritis. This study aims to investigate the therapeutic effects of combined PTX and conventional immunosuppressive regimens on patients with rapidly progressive glomerulonephritis.

Detailed Summary:

Corticosteroids and cytotoxic agents such as cyclophosphamide remain the most commonly used regimens for crescentic glomerulonephritis. However, their use is often limited by adverse effects, most notably life-threatening opportunistic infections due to generalized immunosuppression. Over the past decade, a number of novel experimental therapeutic agents have been shown to ameliorate the severity of experimental crescentic glomerulonephritis. Unfortunately, none of these measures is currently available for clinical use. Other potential agents such as mycophenolate, cyclosporin, and tacrolimus , while clinically available, share similar adverse effects with corticosteroid- and cyclophosphamide-based regimens. PTX is a methylxanthine phosphodiesterase inhibitor that has been widely used to treat peripheral vascular diseases and cerebrovascular disorders. In addition to its well-known hemorheologic activity, accumulating evidence suggests that PTX also possesses potent anti-inflammatory and/or immunoregulatory activities. For examples, PTX has shown its efficacy in different animal models of renal diseases where tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1, or intercellular adhesion molecule-1 is involved. Moreover, clinical trials in patients with diabetic nephropathy and membranous glomerulonephritis have shown that PTX can lower endogenous TNF-alpha and attenuate proteinuria. These data raise the possibility that PTX may have promise as an anti-inflammatory agent via its ability to antagonize inflammatory mediators. Consistent with this idea, we have demonstrated this potential usefulness of PTX in a rat model of accelerated anti-GBM glomerulonephritis. More recently, we have reported that PTX is capable of inhibiting proteinuria via renal MCP-1 production in subnephrotic primary glomerular diseases. In this study, we aim to investigate the potential benefit of combined PTX and conventional
Sponsor: National Taiwan University Hospital

Current Primary Outcome: initiation of acute dialysis or doubling of serum creatinine levels [ Time Frame: 3 months ]

Original Primary Outcome: initiation of acute dialysis or doubling of serum creatinine levels

Current Secondary Outcome: end-stage renal disease (ESRD) [ Time Frame: 6 months ]

Original Secondary Outcome: ESRD (defined by the need for long-term dialysis)

Information By: National Taiwan University Hospital

Dates:
Date Received: July 18, 2006
Date Started: August 2006
Date Completion:
Last Updated: November 12, 2012
Last Verified: October 2012