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.

Highlights

  • MTOR-I effects wound healing through their antiproliferative properties

  • Medications implicated in wound healing complications other than Mammalian target of rapamycin inhibitors (mTOR-I) include mycophenolic acid derivatives [15, 16], steroids [17], and antithymocyte globulin (ATG) [18]

  • Randomized studies which looked at these wound healing complications were thoroughly reviewed. is review focuses on the mechanism of these wound healing complications, how mTOR. is kinase (mTOR)-I affects wound healing, risk factors for wound healing, and the way forward for optimal use of mTOR-I in light of the evidence available from randomized control trials

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Summary

Objective

To study if growth inhibition of MMF on human tenon fibroblasts is mediated by guanosine depletion. Seventy-one percent of obese SRL patients experienced complications compared with 24.3% (p 0.025) of nonobese SRL patients [67] Another retrospective analysis assessed risk factors for wound healing complications in patients receiving de novo SRL, low-dose CsA, and corticosteroid. Multivariate analysis showed that body mass index (BMI) > 26 (odds ratio 2.498, p 0.027) was a significant risk factor for wound healing complications in patients taking SRL. In a prospective randomized trial using high-dose SRL (15–20 ng/mL), wound healing complications increased across all BMI, except patients with a BMI less than or equal to 24 kg/m2. EVL targeting a trough concentration of 3–8 ng/ml avoided the increased rates of lymphocele seen previously, though wound healing events/complications were still slightly higher as compared to MPA (19.8% vs.16.2%) [53]. Later indepth analysis of TRANSFORM data by Tedesco et al found no significant association when wound healing complications were compared with mean EVL concentration during the periods from day 4 to week 4, day 4 to month 2, and day 4 to month 12 [69]

Is It mTOR-I Only?
Mycophenolic Acid Derivatives
Steroids
Uremia and Renal Dysfunction
4.10. Protein-Energy Malnutrition
Review of Randomized Control Trials on mTOR-I
Emergency or Elective Surgery in Patients on mTOR-I
Way Forward for the Use of mTOR-I
Findings
Conclusion
Full Text
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