Malignancies are the third cause of graft loss after kidney transplantation. According to the literature [1,2,3,4] the risk of cancer is 20 times higher than in the general population for non-melanocytic skin neoplasms and 15 times for tumors of the native kidney. Other types of neoplasms occur from 5 to 10 times more frequently than in non-transplanted patients. Malignancies have a negative effect on graft outcomes for both mortality and morbidity related to the tumor itself, and for the reduction of immunosuppression that may facilitate the development of acute or chronic rejection. In this study we wanted to investigate the rates of malignancies and their influence in terms of graft outcomes and if the different immunosuppressive regimens have influence on the development of malignancies in our cohort of transplanted patients.

      We conducted a retrospective observational cohort study to evaluate the occurrence of cancer in our population of kidney-transplanted patients. In our analysis, all transplanted patients in our nephrology unit were stratified in two groups (patients who developed a cancer after transplantation, and patients without cancer). Statistical analysis by means of χ ², T test, odds Ratio when appropriate was performed to evaluate any difference between the two groups in terms of demographic characteristics, graft loss, renal function. Hence, patients with a diagnosis of malignancies after transplantation were stratified in groups according to immunosuppressive regimen to evaluate any difference in terms of rates of malignancies between different anti-rejection drugs. A Cox proportional hazard regression was performed to evaluate if age at transplantation, sex, being re-transplanted, induction therapy with Basiliximab or Thymoglobulin, use of mTOR achieved statistical significance as neoplastic risk factors at the multivariate analysis.

      Of the 750 transplants of our center from 1991 to 2011, 90 patients (12%) developed a malignancy. The tumor was diagnosed after 3,6 ± 2,9 years after transplantation. Patients with neoplasm were male in 72% of cases and older (mean age at transplantation 51,1 ± 10,5 years Vs 47,1 ± 12,6 P <0.01 in nonneoplastic patients). 51% of tumors were of cutaneous origin, (22.2 % squamous cell, 18.8% basal cell, 12,2 Kaposi’s sarcoma) 11 patients had carcinoma of native kidney (12.2%). Each of the other types of cancer were less frequent. (PTLD 5.5%, thyroid 4.4%, breast 3.3%, , bladder 3.3% and prostate 5.5 %). 41 kidneyswere lostin patientswith cancer (45.5%) compared to 186 of the 660 who did not develop tumors (28%) p <0.005 odds ratio: 2.1. In 28 of the 41 cases, graft loss was due to the death with a functioning kidney. The average time of loss of the kidney was 3.0 ± 2.6 years after diagnosis of cancer and 6.2 ± 3.3 years after transplantation. 22 of the 49 patients still in follow-up have chronic renal insufficiency defined as creatinine> 1.4 mg / dL. We observed no cases of malignancies in patients receiving immunosuppressive treatment with mTor, cyclosporine and steroids compared with 22% of patients on cyclosporine, azathioprine and steroids, 13% of those on cyclosporine, mycophenolate, and steroids and 14.2% of patients on cyclosporine and steroids (P <0.05) although the duration of follow up was different between treatment groups (tab 1) . The higher cancer incidence per patient-year was for patients receiving tacrolimus. At the multivariate analysis, only being retransplanted resulted in an increased hazard ratio for developing a malignancy (14.2, p <0.05) while the use of m-TOR had a protective effect (hazard ratio 0,36, p <0,05).

Table 1

Table 1: Type of Neoplasm and Immunosuppressive Regimens

      The onset of cancer after kidney transplantation is a major cause of graft loss because of the higher mortality and morbidity related to the tumor itself. Furthermore, the reduction in immunosuppressive therapy usually made after the diagnosis of cancer can trigger the onset of acute or chronic rejection. Since skin and native kidney are more frequently involved, we strongly recommend following anti neoplastic screening measures (especially yearly dermatologic consulting and renal ultrasound) to recognize early lesions. In our series, the use of m-TOR appears to be protective against the development of malignancies. Since M-tor based protocols were started more recently in our institution, patients with m-tor based regimens have shorter follow up in our series. Nonetheless, since the development of neoplasms is an early event after transplantation the time of our observation can be considered sufficient to confirm an anti-neoplastic protection of m-TOR. Larger, metacentric, prospective studies are needed to confirm these results.