Risk Factors for the Development of Malignancies Post-Transplantation in Kidney Transplant Recipients

<b>Background/Objectives</b>: Malignancies constitute a major cause of death among kidney transplant recipients, and their incidence is increasing globally. We aimed to estimate the frequency of de novo malignancies and identify factors associated with their occurrence among kidney transplant recipients. <b>Methods</b>: Data were derived from the medical records of patients who received a kidney transplant between January 1979 and December 2023 in "Laiko" University Hospital in Athens, Greece. Κidney transplant recipients with a diagnosis of de novo malignancy were compared with recipients without malignancy and were matched for age, sex and year of transplantation. Demographic and clinical characteristics, data on immunosuppression and cancer type were recorded. Multivariate logistic regression was employed to identify possible risk factors for cancer occurrence. <b>Results</b>: Out of 2986 recipients, 268 (8.98%) developed malignancies within a median time of 8 (interquartile range-IQR: 4-16) years after transplantation. Of them, 59.3% were males, the median age at transplantation was 48 (IQR: 39-57) years and the median dialysis vintage was 31.5 (IQR: 9.5-70) months. In addition, 17.2% had a history of rejection. The majority (66.7%) received a combination of mycophenolate and a calcineurin inhibitor with or without steroids. The most frequent malignancies were lung cancer (13%) and post-transplant lymphoproliferative disease (13%), followed by Kaposi sarcoma (8.2%). At diagnosis, 37% had generalized end-stage disease and 19% had aggressive disease with poor prognosis. In multivariate analysis, a history of rejection (odds ratio-OR = 1.75, 95% CI = 1.04-2.94) and glomerulonephritis as primary kidney disease (OR = 2.23, 95% CI = 1.06-4.67) were both significantly associated with malignancy development, whereas immunosuppressive medication was not. <b>Conclusions:</b> Cancer occurrence among kidney transplant recipients was related to the cumulative burden of immunosuppression rather than a specific immunosuppressant.