Sirolimus (SRL) is not nephrotoxic, but it has been shown to increase transforming growth factor (TGF)-β. We investigated the effect of combining mycophenolate mofetil (MMF) with SRL on renal structure and function and on TGF-β. Rats treated with vehicle (VH), MMF 10 mg/kg/d, SRL 0.3 mg/kg/d, or SRL+MMF were killed at 28 days. The physiologic and histologic changes and expression of TGF-β, plasminogen activator inhibitor-1, and extracellular matrix proteins were studied. Although SRL alone did not alter renal function and structure, it increased TGF-β1 mRNA by 44% and protein by 48% (P<0.05 vs. VH). Treatment with MMF did not affect TGF-β1. When combined with SRL, MMF decreased TGF-β1 expression to VH levels. A similar trend was observed with plasminogen activator inhibitor-1 and extracellular matrix proteins. The long-term consequence of increased TGF-β in SRL-treated kidneys remains unknown. However, because MMF can reverse this trend, SRL and MMF combination therapy may be protective.
ASJC Scopus subject areas