Membranoproliferative Glomerulonephritis Medication

  • Author: Pranay Kathuria, MD, MBBS, FACP, FASN; Chief Editor: Vecihi Batuman, MD, FACP, FASN   more...
 
Updated: Jun 20, 2011
 

Medication Summary

Approaches to treatment of membranoproliferative glomerulonephritis (MPGN) have included immunosuppression, inhibiting platelet-induced injury with aspirin and dipyridamole, minimizing glomerular fibrin deposition with anticoagulants, and use of steroidal and nonsteroidal anti-inflammatory agents. Anticoagulant, nonsteroidal, and immunosuppressive (cyclophosphamide) therapies have been found to have minimal beneficial effects and are associated with severe adverse effects.

The standard therapies are steroids for children and antiplatelet therapy for adults. The acceptable evidence-based modalities of treatment of MPGN are summarized in the sections for the specific drug categories.

Other potential treatments of MPGN type II include plasma infusion/plasmapheresis and reducing C3NeF (nephritic factor of the amplification loop). Plasma infusion or plasmapheresis with plasma exchange may provide functionally intact factor H in patients with defined pathologic mutation of the factor H gene.

Strategies to reduce C3NeF include using mycophenolate or rituximab that specifically target CD20 surface antigen expressed on B lymphocytes.[29] Mycophenolate mofetil (MMF) may provide some benefit, but it has not been sufficiently studied.

Jones et al reported that 5 patients with idiopathic MPGN had significant reduction in proteinuria over an 18-month period when they were treated with oral prednisolone and mycophenolate mofetil relative to a control group of 6 patients who did not receive immunosuppression.[32] . No significant change occurred in serum creatinine or creatinine clearance in the treatment group; however, in the control group, serum creatinine and creatinine clearance deteriorated significantly.[32]

New treatments on the horizon include eculizumab, an anti-C5 antibody, to decrease C5 mediated glomerular damage, and sulodexide, a combination of 2 glycosaminoglycans, which may prove to be useful by virtue of its inhibition of glomerular heparanase activity and its interference with inflammatory cells and complement interaction with the glomerular endothelium.[33]

Anecdotal reports describe the benefit of cyclosporine and tacrolimus in steroid-resistant MPGN type II.

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Corticosteroids

Class Summary

Children with idiopathic membranoproliferative glomerulonephritis (MPGN) type I who have nephrotic-range proteinuria, interstitial disease, or renal insufficiency may benefit from corticosteroid therapy. No systemic evaluation of corticosteroid therapy has occurred in adults.

Benefits in children include stabilization of the renal function, slowing of the decline in glomerular filtration rate (GFR), and a decrease in proteinuria. These therapies are associated with multiple complications, including hypertension and seizures in children. Because active inflammation is more likely to be present early in the disease, prompt initiation of therapy may provide better outcomes.

In the International Study of Kidney Disease in Children, investigators suggested the outcome of children with MPGN may be improved with long-term use of prednisone.[34] Alternate-day prednisone was administered for a mean of 130 months; at the end of the study period, approximately 61% of the treatment group had stable renal function relative to 12% of the control group.[34]

The group at Cincinnati has also shown benefit of prolonged alternate-day steroid regimens.[35] Renal survival rates improved, and findings on repeat kidney biopsy at 2 years demonstrated an increase in capillaries with open lumina and a decrease in mesangial matrix and cellularity; however, an increase in glomerular sclerosis and tubular atrophy occurred.[35] The same group reported that patients with membranoproliferative glomerulonephritis type III respond poorly to steroids.[16] Several other studies also documented the benefit of steroid therapy.[36]

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Prednisone

 

Prednisone is an immunosuppressant drug used for the treatment of autoimmune disorders. This agent may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear lymphocyte (PMN) activity.

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Antiplatelet Therapies

Class Summary

Antiplatelet therapies benefit adults with membranoproliferative glomerulonephritis (MPGN). Probable mechanisms that underlie the therapeutic benefits of aspirin include inhibition of platelet aggregation, mesangial proliferation, and alteration of renal hemodynamics. Dipyridamole may enhance the effects of aspirin.

In one study, the use of antiplatelet agents administered over 1 year reduced the incidence of renal failure at 3-5 years, but the renal survival rate was no different at 10 years.[37] Another study using these 2 agents showed significant reduction in proteinuria at 3 years in the treated group.[38] One small uncontrolled study of membranoproliferative glomerulonephritis type I in children found improved outcome and attenuated inflammation on biopsy with the administration of a combination of prednisolone and dipyridamole.[36]

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Aspirin (Bayer Aspirin, Ascriptin, Ecotrin)

 

Aspirin inhibits prostaglandin synthesis, which prevents formation of platelet-aggregating thromboxane A2.

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Dipyridamole (Persantine)

 

Dipyridamole is a platelet adhesion inhibitor that possibly inhibits red blood cell (RBC) uptake of adenosine, itself an inhibitor of platelet reactivity. In addition, this agent may inhibit phosphodiesterase activity, leading to increased cyclic-3', 5'-adenosine monophosphate within platelets and formation of the potent platelet activator thromboxane A2.

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Contributor Information and Disclosures
Author

Pranay Kathuria, MD, MBBS, FACP, FASN  Director, Division of Nephrology and Hypertension, Professor of Medicine, University of Oklahoma School of Community Medicine

Pranay Kathuria, MD, MBBS, FACP, FASN is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Heart Association, American Society of Hypertension, American Society of Nephrology, and National Kidney Foundation

Disclosure: Nothing to disclose.

Specialty Editor Board

F John Gennari, MD  Associate Chair for Academic Affairs, Robert F and Genevieve B Patrick Professor, Department of Medicine, University of Vermont College of Medicine

F John Gennari, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Federation for Medical Research, American Heart Association, American Physiological Society, American Society for Clinical Investigation, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Ajay K Singh, MB, MRCP, MBA  Associate Professor of Medicine, Harvard Medical School; Director of Dialysis, Renal Division, Brigham and Women's Hospital; Director, Brigham/Falkner Dialysis Unit, Faulkner Hospital

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN  Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Medicine Service, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, and International Society of Nephrology

Disclosure: Nothing to disclose.

Acknowledgments

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous authors Martin Senitko, MD, and Sandeep Singh, MD, to the development and writing of the source article.

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Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with lobular accentuation from increased mesangial cellularity. A segmental increase occurs in the mesangial matrix, and the peripheral capillary walls are thickened (hematoxylin and eosin stained section; original magnification × 250). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Electron microscopy of prominent, glomerular, subendothelial, immune-type electron deposits (original magnification × 11,400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Glomerulus with mesangial interposition producing a double contouring of basement membranes, which, in areas, appear to surround subendothelial deposits (Jones silver methenamine–stained section; original magnification × 400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type II. Electron microscopy of glomerular basement membrane, intramembranous, somewhat linear, electron dense deposit (ie, dense deposit disease; original magnification × 11,400). Courtesy of John A. Minielly, MD.
Membranoproliferative glomerulonephritis (MPGN) type I. Immunofluorescent stained section. Intense, peripheral, glomerular, capillary loop deposition of immunoglobulin G (IgG) in an interrupted linear pattern corresponding to extensive subendothelial immune deposits (original magnification × 400). Courtesy of John A. Minielly, MD.
 
 
 
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