Sirolimus, a mammalian target of rapamycin inhibitor, is widely used in transplantation. However, the mechanism by which sirolimus induces adverse effects such as proteinuria and edema remains unclear. To determine whether isolated sirolimus treatment induces proteinuria, we intraperitoneally injected C57BL/6 mice with different doses of sirolimus (0, 3, 10, or 30 mg/[kg[middot]d]) for 24 d. Urinary albumin excretion was then quantified with a double-sandwich enzyme-linked immunosorbent assay, and serum creatinine levels were measured with a single dry-film chemistry auto-analyzer. mRNA expression levels of various genes were also measured by polymerase chain reaction. Urinary albumin was not detected in the sirolimus-treated mice; however, serum creatinine levels were found to increase in a dose-dependent manner and were significantly higher in the group treated with sirolimus than for the control. Glomerular mRNA expression profiling showed decreased levels of podocyte-related genes (WT-1, synaptopodin, nephrin, CD2AP, and podocin), and the fibrosis marker TGF-beta in the sirolimus-treated mice. Also, the proteins levels were decreased by sirolimus treatment. Furthermore, reduced expression of the antiapoptotic genes Bcl-2 and Bcl-xL was seen. Although sirolimus treatment decreased the expression of slit diaphragm-associated genes and increased serum creatinine levels, it failed to induce proteinuria in this model. Further studies are required to evaluate the condition in which sirolimus induces proteinuria.

CITATION INFORMATION: Kim B, Cho Y, Lee H, Joo D, Huh K, Kim M, Kim Y. Effect of Isolated Intraperitoneal Sirolimus Treatment on the Kidneys of C57BL/6 Mice. Am J Transplant. 2016;16 (suppl 3).

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