Mammalian Target of Rapamycin Inhibitors and Wound Healing Complications in Kidney Transplantation: Old Myths and New Realities

Abstract

Mammalian target of rapamycin inhibitors (mTOR-I) lacks nephrotoxicity, has antineoplastic effects, and reduces viral infections in kidney transplant recipients. Earlier studies reported a significant incidence of wound healing complications and lymphocele. This resulted in the uncomfortable willingness of transplant clinicians to use these agents in the immediate posttransplant period. As evidence and experience evolved over time, much useful information became available about the optimal use of these agents. Understandably, mTOR-I effects wound healing through their antiproliferative properties. However, there are a lot of other immunological and nonimmunological factors which can also contribute to wound healing complications. These risk factors include obesity, uremia, increasing age, diabetes, smoking, alcoholism, and protein-energy malnutrition. Except for age, the rest of all these risk factors are modifiable. At the same time, mycophenolic acid derivatives, steroids, and antithymocyte globulin (ATG) have also been implicated in wound healing complications. A lot has been learnt about the optimal dose of mTOR-I and their trough levels, its combinations with other immunosuppressive medications, and patients’ profile, enabling clinicians to use these agents appropriately for maximum benefits. Recent randomized control trials have further increased the confidence of clinicians to use these agents in immediate posttransplant periods.

Relevance of NLRP3 Inflammasome-Related Pathways in the Pathology of Diabetic Wound Healing and Possible Therapeutic Targets

“…The effect of rapamycin on wound healing whether delaying or promoting wound healing has been of concern [ 118 ]. Although rapamycin impairs wound healing in kidney transplantation that is associated with their antiproliferative properties [ 119 ], it is also regarded as a potential therapeutic drug for DW healing that suppresses the phosphorylation of mTOR and subsequent NF- κ B-mediated NLRP3 inflammasome [ 120 ]. The effects of the Wnt signaling pathway on the wound healing process could be attributed to the promotion of angiogenesis and amelioration of the inflammatory response [ 121 ].…”

Immunomodulators for Non-Melanoma Skin Cancers: Updated Perspectives

“…Wound healing complications have also been observed with the use of mTOR inhibitors, 66 and special consideration must be made to reduce the risk of post-operative complications, especially in patients with other risk factors for poor wound healing. 67 …”

“…Wound healing complications have also been observed with the use of mTOR inhibitors, 66 and special consideration must be made to reduce the risk of post-operative complications, especially in patients with other risk factors for poor wound healing. 67 Currently, the NCCN guidelines version 2.2022 for the management of cSCC note that consideration should be given to either reduce the level of immunosuppression and/or incorporate mTOR inhibitors into the immunosuppressive regimen of SOTRs in cases of life-threatening skin cancer, or the rapid development of multiple tumors. (Table 1) Expert consensus suggests that revision of immunosuppression should also be considered in SOTRs at risk for significant disease burden or poor outcomes from cSCC.…”