Sirolimus - The negative aspects

A recent article in Kidney International discusses the negative and positive aspects of this interesting drug- sirolimus, mTOr inhibitor.  Initially designed to fight renal cancer, fast caught on to treat rejection and be used as an immunosuppression.
1. Six trials so far have randomized sirolimus vs a calcineurin inhibitor that were mentioned in this article. They all had more acute rejection episodes with sirolimus. So graft survival is a concern.
2. Renal toxicity has been described- from TMA to collapsing FSGS and severe proteinuria making it not as promising as CNI. But CNI have a more chronic toxicity to the kidney
3. Dyslipidemia has been noted as well more with this agent. - close to 60% of the patients getting mTor in clinical trials required lipid lowering agents
4. NODAT was also noted to be higher in this group; 25% more chance than CNI
5. Wound healing:- preventing the surgical wound healing or in future if patients need other surgeries makes it tough.
6. Other- mouth ulcers, myelosuppresion and infertility were more common in this agent as well.
7. Finally, they mention the new findings lately described pulmonary toxicities that are leading to a restrictive disease in the lung.

Ref:
http://www.ncbi.nlm.nih.gov/pubmed/20703217