Introduction: After kidney transplantation (KT), the incidence of non-melanoma skin cancer increases and ranks first among cancers. Immunosuppressive drugs have general effects such as reducing viral clearance and disrupting DNA repair mechanisms. Calcineurin inhibitors(CNI)are also reported to have direct carcinogenic effects such as increasing IL-6, TGF-ß, VEGF production and angiogenesis, and B cell proliferation.Everolimus(EVO), an immunosuppressive drug of the mTORi group has been shown to reduce IL-10 synthesis, to inhibit EBV-mediated B cell proliferation and VEGF, and act antiangiogenic; therefore, it has been approved for the treatment of some types of cancer. One of the approaches used today after the diagnosis of skin cancer is to discontinue mycophenolate mofetil(MMF)or azathioprine(AZA)and switch to a combination of tacrolimus(TAC) and EVO.There is limited data on the use of protocols that do not include CNI. This observational study aimed to investigate the results of the combination of MMF, EVO and steroid without CNI in this patient group, in terms of graft functions.
Method: The results of 18 patients who underwent KT in a single center between 2015 and 2020 and were administered a combination of MMF and EVO after discontinuing TAC were evaluated. Drug change was made for squamous cell carcinoma in 10 patients, for basal cell carcinoma in 2 patients, and for CNI toxicity in 6 patients.
Results: Fourteen of the patients were male, the average age was 49±14, and 16 of 18 patients had living donor KT. All patients were PRA negative before KT. All received ATG induction, average dose was 694mg.±271(350-1500). The primary immunosuppressive protocol consisted of steroids, MMF and TAC. Three patients had a history of acute rejection within the first 3 months after KT. The average creatinine level of the patients in the first year was 1.23 ±0,28 (0.7-1.7) mg/dl. Conversion took place on average 36 ±25,3(6.4-92) months after KT. The follow-up period after medication change was 49±27,9(5-95) months. Serum creatinine values ​​before conversion and approximately 6 months after conversion were 1.2 and 1.1 mg/dl (ns). No rejection was observed in any patient after the change. During the follow-up, short-term leukopenia was observed in 3 patients, which resolved without intervention, and as it persisted in 1 patient, the MMF dose was reduced to 1 gram. None of them developed infection. There was no significant change in hemoglobin levels. The dose of MMF used was 2 grams/day for 6 months and then 1.5 grams/day in 1 patient,1 gram/day in 2 patients and 1.5 grams/day in the others. There was no significant change in proteinuria values. The average EVO level was 4.5 ng/mL at the 1st year after conversion.
Conclusion: In the presence of skin cancer and non-immunological allograft damage, the combination of MMF and EVO with steroids did not have a negative effect on the course of graft functions and proteinuria. Its use may be considered as an alternative to the combination of TAC and EVO.