Maleic vinyl ether anhydride nephropathy: altered glomerular permeability due to an immunomodulating agent.
The polyanionic immunomodulatory polymer, maleic vinyl ether anhydride (MVE-2), enhances antitumor macrophage activity and causes heavy proteinuria. The effects of this compound on renal function and renal morphology were investigated in a rat model. Rats were given daily intravenous infusions of MVE-2, 100 mg/kg, over 2-4 hr on each of three consecutive days. Renal function and morphology in MVE-2-infused rats were examined by standard techniques and compared to control rats given saline. On the average, MVE-2 rats had a significant reduction in inulin clearance to 62% of control values. MVE-2 rats developed heavy proteinuria 1-3 days after the first infusion (mean +/- 1 SEM, 387 +/- 91 mg/24 hr). By light microscopy, the only finding was intratubular protein casts; glomeruli were normal. Immunofluorescence showed no deposition of antibody, complement, or fibrin. Electron microscopy revealed foot process effacement, epithelial cell vacuolization, and subepithelial ring-shaped structures; no immune-complex deposits were present. MVE-2 rats had no increase in the number of glomerular Ia(+) cells. To examine further the mechanism of MVE-2 nephropathy, the ability of MVE-2 to induce proteinuria in animals pretreated with radiation (750 rad), methylprednisolone (MP) or cyclosporine (CyA) was determined. Animals pretreated with radiation or MP had significantly less proteinuria after MVE-2 treatment compared to animals receiving no immunosuppressive therapy, while CyA pretreated rats developed heavy proteinuria. These results are compatible with the hypothesis that MVE-2 induces proteinuria via an effect on steroid- and radiation-sensitive cells, perhaps related to production of circulating factors which alter glomerular permeability.
Bertolatus
J A
JA
Department of Internal Medicine, University of Iowa College of Medicine, Veterans Administration Medical Center, Iowa City 52240.
D000818:Animals; D004195:Disease Models, Animal; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007674:Kidney Diseases / Q000139:chemically induced* / Q000276:immunology; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D011108:Polymers / Q000009:adverse effects*; D011713:Pyran Copolymer / Q000009:adverse effects* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains
D000949:Histocompatibility Antigens Class II; D011108:Polymers; D011713:Pyran Copolymer