Abstract
Background and Aims
One of the major immunosuppression-related complications of kidney transplant (KT) is the increased risk of cancer development. KT patients have at least a twofold higher risk of developing or dying from cancer than the general population. Indeed, malignancy is currently the second most common cause of death after cardiovascular disease in these patients. After the substantial rise in post-transplant graft survival in the last decades, the present study aims to evaluate the post–KT cancer incidence, the mortality risk and associated risk factors in two transplant centres over a long period of time.
Method
A retrospective cohort study used clinical and epidemiological information among KT patients transplanted between 1993 and 2017 in two renal transplant centres in Italy and diagnosed with de novo cancers (DNC). Data on vital status and graft loss were available for most subjects and assessed in December 2019. Survival analyses were performed using parametric survival models assuming a Weibull distribution of the baseline hazard; these models were used to test the association between predictors measured at baseline and a) time from KT to development of DNC, and b) time from development of DNC to death, loss to follow-up or administrative censoring, whichever occurred first. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained. Kaplan–Meier curves were generated. A p-value < 0.05 was considered as statistically significant. Data were analyzed using Stata.
Results
In the present study, 201 DNCs were diagnosed in subjects who underwent KT between 1993 and 2017. Median follow-up after kidney transplantation was 12.1 years (IQR: 7.0–17.5). The proportion of subjects who received allograft from deceased donor was 89%, 61% had 4 or more mismatches, 68% were male. At the time of KT, the average age was 52.4±12.3 years and renal replacement therapy (RRT) vintage was 39 months (IQR: 22–69). The incidence rate of DNC for the whole cohort was 145 per 1,000 person-years, with a median time to cancer from KT of 5.5 years (IQR: 2.8–10.5) [Figure 1]. Skin cancers accounted for most cases (59%), followed by solid tumors (30%), post-transplant lymphoproliferative disorders (6%), Kaposi’s sarcoma (3%) and other malignancies (2%). In the multivariable model, increasing age was significantly associated with time to development of DNC (HR for 1 year 1.03, 95% CI 1.01, 1.04; p = 0.001). Induction therapy with a combination of rabbit antithymocyte globulin and basiliximab resulted to be a risk factor for time to DNC (HR compared with none 3.16, 95% CI 2.04, 4.91; p < 0.001). None of the following pre- and peri-transplant predictors was significantly associated with time to DNC: RRT vintage and technique, episodes of acute rejection, chronic kidney disease etiology, presence of delayed graft function, type of donor (deceased or living), number of mismatches. The incidence rate of death for the whole cohort was 47 per 1,000 person-years [Figure 2]. According to type of cancer, death incidence rate was 73, 56, 34 per 1,000 person-years for solid tumors, non-solid and non-skin tumors (i.e PTLD, Kaposi and other tumors) and skin cancer, respectively. In multivariable analysis, age at time of cancer (HR for 1 year 1.04, 95% CI 1.00, 1.07; p = 0.037) and previous acute rejection (HR 2.51, 95% CI 1.23, 5.11; p = 0.011) were significantly associated with time to death.
Conclusion
In a large sample of KT recipients with DNC, age and type of induction therapy were significantly associated with time to development of cancer. Age and previous acute rejection were significant predictors of death after DNC. Epidemiological studies could help in risk estimation of graft and patient survival after cancer development and guide in post KT clinical care.
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