Nephrology Dialysis Transplantation, Vol 13, Issue 10 2501-2508, Copyright © 1998 by Oxford University Press
M Kobayashi, K Muro, K Yoh, M Kondoh, S Iwabuchi, K Hirayama, T Ishizu, S Kikuchi, N Yamaguchi and A Koyama
Background. There have been no reports on the effect
of FK506, a new immunosuppressive agent, on experimental membranous
glomerulonephritis (MN) induced by an exogenous antigen. Therefore we
investigated the effects of FK506 on MN induced by cationized bovine serum
albumin (C-BSA) in rats. Methods. Two weeks after the
rats were immunized with 1 mg of C-BSA and Freund's complete adjuvant, they
received intravenous injections of 3 mg/kg of C-BSA 3 times weekly for 4
weeks. Rats were divided into four groups: group A
(n=5) received intramuscular injections of 3 mg/kg of
FK506 daily for 5 days beginning 2 days before the first immunization;
group B (n=4) received 1 mg/kg of FK506 daily for 2
weeks beginning 2 weeks after the first immunization. Group D
(n=5) received no FK506 and served as the control
group. Rats were sacrificed 8 weeks after the first immunization.
Results. Administration of FK506 in the
preimmunization stage almost completely suppressed the development of MN in
group A. Histological findings in groups B and C were similar to those in
group D, the control group. However, urinary protein excretion was
significantly lower in the group B(24±46 mg/day) and C
(220±44 mg/day) than in group D (330±61 mg/day).
Expression of intracellular adhesion molecule-1 in glomeruli and the number
of leukocyte functioning-associated molecules-1 were significantly
decreased in groups A, B, and C compared with the control group.
Administration of FK506 was not associated with any significant
side-effects or histological abnormalities. The whole-blood trough levels
of FK506 in groups B and C were 9.1 ng/ml and 9.2 ng/ml respectively.
Conclusions. The efficacy of FK506 was significantly
increased when the drug was administered in the early phase of immunization
in this model. The present study suggests that FK506 may be useful in
patients with intractable nephrotic syndrome such as MN.
Keywords: cationized BSA; exogenous antigen;
experimental membranous glomerulonephritis; FK506; proteinuria
ORIGINAL ARTICLES
Effects of FK506 on experimental membranous glomerulonephritis induced by cationized bovine serum albumin in rats
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Corresponding author address: Department of Nephrology, Tokyo Medical University Kasumigaura Hospital, Ami, Inashiki, Ibaraki, 300-0395 Japan
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