Hyperlipidemia and thrombocytopenia, as well as leukopenia are known side affects of sirolimus administration, an immunosuppresant used in the treatment of acute rejection.
Sirolimus, cyclosporine, and steroids are a commonly used immunosuppressive regimen in renal transplants. The immunosuppressive effects of sirolimus are mediated by its ability to bind mTOR and thereby inhibit T-cell proliferation in response to IL-2. This differentiates it from cyclosporine which works by inhibiting calcineurin.
Beebe et al. report that ADPKD is one of the most commonly inherited diseases in the United States and affects nearly 500,000 Americans. Because it accounts for 5 to 10 percent of patients with end-stage renal disease, it is also a common indication for renal transplantation. Diagnosis is usually made in middle age, when complications such as hypertension, pain and hematuria develop. Dialysis and renal transplantation are used to treat patients who develop renal failure.
Soefje et al. review toxicities associated with mTOR inhibitors. They report that metabolic toxicities, including hyperglycemia, hyperlipidemia, and hypophosphatemia, are some side effects of various mTOR inhibitors.
Illustration A shows the mechanism of action of sirolimus. Sirolimus binds the cytosolic protein FKBP12. The sirolimus-FKBP12 complex inhibits the mTOR pathway by directly binding the mTOR Complex1 (mTORC1).
Answer 1: Nephrotoxicity and hypertension are known side effects of daclizumab.
Answer 2: Pancreatitis is a rare side effect of azathioprine.
Answer 4: Muromonab-CD3 (OKT3) can provoke the cytokine release syndrome and hypersensitivity reactions.
Answer 5: Nephrotoxicity and gingival hyperplasia are known side effects of cyclosporine. For this reason, sirolimus is often preferred in patients with renal failure.
Beebe DK. Autosomal dominant polycystic kidney disease. Am Fam Physician. 1996 Feb 15;53(3):925-31. Review. PubMed PMID: 8594868.
PMID:8594868 (Link to Abstract)
Soefje SA, Karnad A, Brenner AJ. Common toxicities of mammalian target of rapamycin inhibitors. Target Oncol. 2011 Jun;6(2):125-9. doi: 10.1007/s11523-011-0174-9. Epub 2011 Apr 16. Review
PMID:21499766 (Link to Abstract)
USMLE World Step 1 QBank Question #1155. Copyright © USMLEWorld, LLC 2012