Effects of rapamycin on active Heymann nephritis. 2007

Radomir Naumovic, and Djurdjica Jovovic, and Gordana Basta-Jovanovic, and Zoran Miloradovic, and Nevena Mihailovic-Stanojevic, and Tamara Aleksic, and Dijana Jovanovic
Clinic of Nephrology, Clinical Center of Serbia, Belgrade, Serbia. rnaumovic@drenik.net

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.

UI MeSH Term Description Entries
D007166 Immunosuppressive Agents Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging. Immunosuppressant,Immunosuppressive Agent,Immunosuppressants,Agent, Immunosuppressive,Agents, Immunosuppressive
D008297 Male Males
D011507 Proteinuria The presence of proteins in the urine, an indicator of KIDNEY DISEASES. Proteinurias
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015433 Glomerulonephritis, Membranous A type of glomerulonephritis that is characterized by the accumulation of immune deposits (COMPLEMENT MEMBRANE ATTACK COMPLEX) on the outer aspect of the GLOMERULAR BASEMENT MEMBRANE. It progresses from subepithelial dense deposits, to basement membrane reaction and eventual thickening of the basement membrane. Heymann Nephritis,Membranous Glomerulopathy,Nephropathy, Membranous,Extramembranous Glomerulopathy,Idiopathic Membranous Glomerulonephritis,Idiopathic Membranous Nephropathy,Membranous Glomerulonephropathy,Membranous Nephropathy,Glomerulonephritides, Idiopathic Membranous,Glomerulonephritides, Membranous,Glomerulonephritis, Idiopathic Membranous,Glomerulonephropathy, Membranous,Glomerulopathy, Extramembranous,Glomerulopathy, Membranous,Idiopathic Membranous Glomerulonephritides,Membranous Glomerulonephritides,Membranous Glomerulonephritides, Idiopathic,Membranous Glomerulonephritis,Membranous Glomerulonephritis, Idiopathic,Membranous Nephropathy, Idiopathic,Nephritis, Heymann,Nephropathy, Idiopathic Membranous
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D050533 Glomerular Basement Membrane The layer of EXTRACELLULAR MATRIX that lies between the ENDOTHELIUM of the glomerular capillaries and the PODOCYTES of the inner or visceral layer of the BOWMAN CAPSULE. It is the product of these two cell types. It acts as a physical barrier and an ion-selective filter. Basement Membrane, Glomerular,Basement Membranes, Glomerular,Glomerular Basement Membranes,Membrane, Glomerular Basement,Membranes, Glomerular Basement
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D018414 CD8-Positive T-Lymphocytes A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. Suppressor T-Lymphocytes, CD8-Positive,T8 Cells,T8 Lymphocytes,CD8-Positive Lymphocytes,Suppressor T-Cells, CD8-Positive,CD8 Positive Lymphocytes,CD8 Positive T Lymphocytes,CD8-Positive Lymphocyte,CD8-Positive Suppressor T-Cell,CD8-Positive Suppressor T-Cells,CD8-Positive Suppressor T-Lymphocyte,CD8-Positive Suppressor T-Lymphocytes,CD8-Positive T-Lymphocyte,Cell, T8,Cells, T8,Lymphocyte, CD8-Positive,Lymphocyte, T8,Lymphocytes, CD8-Positive,Lymphocytes, T8,Suppressor T Cells, CD8 Positive,Suppressor T Lymphocytes, CD8 Positive,Suppressor T-Cell, CD8-Positive,Suppressor T-Lymphocyte, CD8-Positive,T-Cell, CD8-Positive Suppressor,T-Cells, CD8-Positive Suppressor,T-Lymphocyte, CD8-Positive,T-Lymphocyte, CD8-Positive Suppressor,T-Lymphocytes, CD8-Positive,T-Lymphocytes, CD8-Positive Suppressor,T8 Cell,T8 Lymphocyte
D020123 Sirolimus A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties. Rapamycin,AY 22-989,I-2190A,Rapamune,AY 22 989,AY 22989,I 2190A,I2190A

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