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.
Corticosteroids
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)
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)
For pulse therapy. Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Cytotoxins
Class Summary
Inhibit cell growth and proliferation.
Cyclophosphamide (Cytoxan)
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)
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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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.
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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).
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Diffuse proliferative glomerulonephritis (DPGN). Using electron microscopy, electron-dense deposits are visible in the mesangial, subendothelial, intramembranous, and subepithelial locations.
