Background/Aim: The new immunosuppressant SDZ RAD, a rapamycin derivative, inhibits
growth factor driven cell proliferation. SDZ RAD designed for transplantation may
also be a candidate agent to treat inflammatory kidney diseases. Therefore, we investigated
the effects of SDZ RAD in two different animal models of glomerulonephritis, in anti-
Thy1.1 nephritis and in acute puromycin aminonucleoside (PAN) nephrosis. Methods:
Eighty-seven male Wistar rats were investigated. Anti-Thy1.1 nephritis: healthy rats
(n = 9), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 9), SDZ RAD placebo
treated nephritic rats (n = 6), SDZ RAD-pretreated nephritic rats (n = 9), and early
(n = 6) as well as delayed (n = 6) SDZ RAD-posttreated nephritic rats. PAN nephrosis:
healthy rats (n = 6), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 12),
and SDZ RAD-pretreated nephritic rats (n = 12). In a separate study, 12 male Sprague-Dawley
rats were analyzed in anti-Thy1.1 nephritis: healthy rats (n = 3), nephritic rats
(n = 3) and pretreated nephritic rats (n = 6). SDZ RAD and SDZ RAD placebo were given
at single doses of 2.5 mg/kg body weight per day by gavage. The experiments lasted
until days +2 and +9 after induction of anti-Thy1.1 nephritis and until day +13 in
the case of PAN nephrosis. Results: In anti-Thy1.1 nephritis, SDZ RAD demonstrated
marked proinflammatory effects in a time-dependent manner, as reflected by severe
focal damage to glomerular histology including inhibition of mesangial cell proliferation,
reduction of creatinine clearance, and increase in plasma creatinine levels as well
as proteinuria. Almost identical results were obtained in both rat strains. In contrary,
SDZ RAD ameliorated significantly the development of PAN nephrosis. Animals pretreated
by this agent showed a significant reduction of proteinuria and of glomerular invasion
of monocytes/macrophages. Conclusion: Some caution is warranted for the use of SDZ
RAD in inflammatory glomerular diseases, since it accentuated glomerular damage induced
by anti-Thy1.1 antibodies.