**6.19. Everolimus**

leading to hypomagnesemia and hypokalemia. De novo development of proteinuria, or exaggeration of preexisting proteinura is seen with conversion to sirolimus.[37] Use of sirolimus is in fact contraindicated if patient has 24 hour urine protein exceeding 1 gram/day. Sirolimus has been reported to have a direct toxic effect on podocytes. [38] [39] Sirolimus associated cast nephropathy has been reported as well. [40] Thrombotic microangiopathy has also been observed with sirolimus use, likely mediated by its inhibition of VEGF pathway. [41] The discontinuation rate of Sirolimus was as high as 30% in clinical studies due to adverse

Use of sirolimus is not recommended immediately after transplant surgery as sirolimus impairs wound healing (by inhibiting fibroblast proliferation). Sirolimus can increase the risk of lymphocele formation and is also associated with prolonged recovery from delayed graft function. [45]. Due to its effects on tissue repair, sirolimus is generally stopped few weeks prior to any anticipated elective surgery. Metabolic side effects of sirolimus include hyperlipidemia and hyperglycemia. Sirolimus use is also associated with non-infectious atypical pneumonitis. Bactrim is typically prescribed for one year as there are studies observing fatal pneumocystis pneumonia with sirolimus use. Sirolimus also suppresses bone marrow leading to cytopenias. Cell counts should be closely monitored especially when used in combination with MMF.

reactions. [42-44]

Table 3 pg. 14

**penia**

**Healing**

**Diabetes**

**Hyperuricemia**

Patients also can develop oral ulcers with this agent.

218 Current Issues and Future Direction in Kidney Transplantation

**Nephrotoxicity** ↑ ↑

**GI side effects** ↑ ↑↑

**Anemia/Leuko** ↑ ↑

**Delayed Wound** ↑

**↑: mild-moderate adverse effect on the complication ↑↑: moderate-severe adverse effect on the complication**

**Table 3.** Adverse Effects Of Maintenance Immunosuppressive agents

↑: mild-moderate adverse effect on the complication ↑↑: moderate-severe adverse effect on the complication

**Proteinuria** ↑↑

**Osteopenia** ↑ ↑ ↑↑

**Tac, Tacrolimus; CsA, Cyclosporine; mTORi, mammalian target of rapamycin inhibitor; MMF, mycophenolate mofetil**

Tac, Tacrolimus; CsA, Cyclosporine; mTORi, mammalian target of rapamycin inhibitor; MMF, mycophenolate mofetil

**New Onset** ↑↑ ↑ ↑ ↑

**Hyperlipidemia** ↑ ↑↑ ↑

**Hypertension** ↑↑ ↑↑

**Adverse Effects Tac CsA mTORi MMF Steroids**

There are recent studies on use of everolimus in kidney transplant recipients. [46] It is similar to sirolimus in terms of mechanism of action and side effect profile. The only major difference from sirolimus is its shorter half life.
