Effects of rapamycin on active Heymann nephritis.
OBJECTIVE
The effects of rapamycin (RAPA) were examined in active Heymann nephritis (HN), an experimental model of human membranous nephropathy (MN). Current opinion on the therapy of MN is controversial, and medications used for its treatment have not yielded the expected results.


METHODS
In a two-part study, we examined the effects of RAPA (1.5 mg/kg/day) during the induction phase of HN and on the evolving disease. In both parts, control groups of immunized rats not treated with RAPA and control groups of unimmunized rats were observed and sacrificed concurrently with the treated groups.


RESULTS
During the induction phase no significant changes in proteinuria were observed in the group treated with RAPA, in comparison to those in the untreated group (p < 0.001). During the evolving disease RAPA significantly lowered proteinuria (p < 0.001). The characteristic pathohistologic changes and IgG depositions along the glomerular basement membrane were considerably diminished, and infiltration of CD8+ cells completely prevented.


CONCLUSIONS
RAPA demonstrated beneficial effects on disease progression, given either in the induction phase or during evolving HN. It would be desirable to investigate the effect of RAPA on patients with MN.
Naumovic
Radomir
R
Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia. rnaumovic@drenik.net
Jovovic
Djurdjica
D
Basta-Jovanovic
Gordana
G
Miloradovic
Zoran
Z
Mihailovic-Stanojevic
Nevena
N
Aleksic
Tamara
T
Jovanovic
Dijana
D
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D050533:Glomerular Basement Membrane / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D020123:Sirolimus