Evaluation of the ameliorative effects of immunosuppressants on crescentic glomerulonephritis in SCG/Kj mice.
The therapeutic efficacy of immunosuppressants for treating rapidly progressive glomerulonephritis (RPGN) with crescent formation remains controversial. SCG/Kj mice spontaneously develop RPGN-like symptoms, characteristic of crescentic glomerulonephritis and systemic small vessel vasculitis, associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA). We evaluated the "ameliorative", not prophylactic, effects of immunosuppressive agents, deoxyspergualin (DSG), cyclophosphamide (CYC) and prednisolone (PDN), on RPGN in these mice. DSG at intraperitoneal doses of 3 and 6 mg/kg, CYC at an oral dose of 12 mg/kg, or PDN at an intraperitoneal dose of 120 mg/kg was administered once a day for 21 days to female mice "at the onset of hematuria". A set of control SCG/Kj mice received only saline injections. DSG and CYC significantly prolonged survival, improved the proteinuria, hematuria and hyperuremia, and decreased the serum level of myeloperoxidase-ANCA. Moreover, DSG significantly suppressed the formation of crescents in glomeruli. PDN failed to affect any of the parameters. DSG might be useful for inducing remission in crescentic glomerulonephritis involved in RPGN.
Saiga
Kan
K
Pharmaceutical Research Laboratories, Nippon Kayaku Co. Ltd., Tokyo, Japan.
Yoshida
Minako
M
Nakamura
Iwao
I
Toyoda
Eriko
E
Tokunaka
Kazuhiro
K
Morohashi
Hirohisa
H
Abe
Fuminori
F
Nemoto
Kyuichi
K
Nose
Masato
M
D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000378:metabolism; D001772:Blood Cell Count; D001806:Blood Urea Nitrogen; D001835:Body Weight; D015267:Churg-Strauss Syndrome / Q000235:genetics; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006146:Guanidines / Q000627:therapeutic use*; D006417:Hematuria / Q000097:blood / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009195:Peroxidase / Q000378:metabolism; D016019:Survival Analysis; D016482:Urinalysis
D019268:Antibodies, Antineutrophil Cytoplasmic; D006146:Guanidines; D007166:Immunosuppressive Agents; D009195:Peroxidase; C037258:gusperimus