Medication Summary

Corticosteroids and cytotoxic therapy can induce remission. Corticosteroids are potent anti-inflammatory agents and immunosuppressants. These drugs suppress cellular and humoral response to tissue injury, thereby reducing inflammation. Oral prednisone generally is required for maintenance therapy. Cytotoxic drugs induce alkylation of DNA.

Class Summary

These agents have anti-inflammatory (glucocorticoid) and salt-retaining (mineralocorticoid) properties. Glucocorticoids have profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)

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Most patients require long-term oral prednisone after inducing remission. Immunosuppressants for treatment of autoimmune disorders may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.

Methylprednisolone (Solu-Medrol)

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For pulse therapy. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Inhibit cell growth and proliferation.

Cyclophosphamide (Cytoxan)

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DOC in DPGN. Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.

Low dose is used when creatinine clearance is < 33 mL/min.

Maintain white blood cell count >2000/mL.

A dose of 50-100 mg/m² PO qd is associated with a higher incidence of hemorrhagic cystitis.

Mycophenolate (CellCept, Myfortic)

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Inhibits inosine monophosphate dehydrogenase (IMPDH) and suppresses de novo purine synthesis by lymphocytes, thereby inhibiting their proliferation. Inhibits antibody production.

Two formulations are available and are not interchangeable. The original formulation, mycophenolate mofetil (MMF, Cellcept) is a prodrug that once hydrolyzed in vivo, releases the active moiety mycophenolic acid. A newer formulation, mycophenolic acid (MPA, Myfortic) is an enteric-coated product that delivers the active moiety.

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Media Gallery

Light microscopy (trichrome stain) shows globally increased cellularity, numerous polymorphonuclear cells, cellular crescent (at left of photomicrograph) and fibrinoid necrosis (brick red staining at right of photomicrograph). These findings are characteristic of diffuse proliferative glomerulonephritis.
Diffuse proliferative glomerulonephritis (DPGN). Immunofluorescent microscopy shows (except for anti–glomerular basement membrane [GBM] disease) a granular deposition of immunoglobulins, complement, and fibrin along the GBM, tubular basement membranes, and peritubular capillaries (image 2a). Linear deposition occurs in the GBM in anti-GBM disease (image 2b).
Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.

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Author

Moro O Salifu, MD, MPH, FACP Associate Professor, Department of Internal Medicine, Chief, Division of Nephrology, Director of Nephrology Fellowship Program and Transplant Nephrology, State University of New York Downstate Medical Center

Moro O Salifu, MD, MPH, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Transplantation, American Society of Diagnostic and Interventional Nephrology, American Medical Association, American Society for Artificial Internal Organs, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Coauthor(s)

Barbara G Delano, MD, MPH, FACP Professor and Chair, Department of Community Health Sciences, School of Public Health, State University of New York Downstate

Barbara G Delano, MD, MPH, FACP is a member of the following medical societies: American Society of Nephrology, International Society of Nephrology, National Kidney Foundation, Sigma Xi, The Scientific Research Honor Society

Disclosure: Nothing to disclose.

Specialty Editor Board

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

Disclosure: Received salary from Medscape for employment. for: Medscape.

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, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Interim Chair, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

James H Sondheimer, MD, FACP, FASN Professor of Medicine, Division Chief, Nephrology and Hypertension, Department of Medicine, Wayne State University School of Medicine; Medical Director, DaVita Kresge Dialysis (Detroit)

James H Sondheimer, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology

Disclosure: Nothing to disclose.

Sections Diffuse Proliferative Glomerulonephritis
Overview
Presentation
DDx
Workup
Treatment
Guidelines
Medication
Media Gallery
References

Diffuse Proliferative Glomerulonephritis Medication

Medication Summary

Corticosteroids

Class Summary

Prednisone (Deltasone, Orasone, Meticorten, Sterapred)