Cancer incidence after immunosuppressive treatment following kidney transplantation

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Abstract

Cancer incidence is increased in renal transplant recipients due to immunosuppressant treatment that should be maintained to prevent and treat acute rejection. Use of new and very potent immunosuppressants has made it possible to reduce acute rejection incidence and improve renal graft survival, although increase of infections and post-transplant neoplasms have become clearer. On the other hand, renal transplant candidates who remain on dialysis have a greater prevalence of neoplasms than the age-matched general population, either because the neoplasm was the cause of their renal failure (multiple myeloma or kidney or urinary tract cancers) or because their renal disease entails a risk for cancer development (acquired cystic disease or analgesic nephropathy).

Practically, all de novo neoplasms have a greater incidence in renal transplant patients. Cutaneous neoplasms are the most prevalent in renal transplant recipients and their incidence increases with transplant time. Post-transplant lymphoproliferative diseases are more frequent in patients who receive greater immunosuppression (antithymocyte/antilymphocyte globulin or OKT3) or are infected de novo by Epstein Barr Virus (EBV) through the transplanted kidney. Kaposi's sarcoma has a high incidence in the renal transplanted population, does not appear in the general population, and is related with Human Herpes Virus 8 (HHV-8) infections. The incidence of tumors in non-functioning native kidneys is especially high in renal transplant due to the presence of acquired cystic disease or analgesic nephropathy.

Gold standards of post-transplant de novo renal neoplasm prevention are modulating immunosuppression and avoiding exposure to sunlight and to different oncogenic viruses (EBV, cytomegalovirus, hepatitis B and C viruses).

Introduction

Renal transplant is the treatment of end-stage renal failure that provides the best quality of life to the patient. However, the immunosuppressant treatment necessary for long-term renal transplant functioning has a series of short and long-term side effects, such as infections, increased cardiovascular risk and neoplastic diseases, which can be life-threatening for the patient.

De novo cancer is a major complication of renal transplant that causes significant short and long-term mortality. It accounts for 20% of the exitus of renal transplant patients every year and accounts for 30% of the death causes of the renal transplant recipients with a follow-up greater than 20 years [1].

The main information on cancer in the renal transplanted patient comes from the Cincinnati Transplant Tumor Registry (CTTR), elaborated by Penn since the 1970 [2], [3], [4], [5], from the Nordic Renal Transplant Registry (NRTR) that includes cases from Scandinavian countries [6], [7], [8], [9] and the Australian and New Zealand Transplant Registry (ANTR) [10], [11], [12]. In addition to these registries, there are many studies from a single center or regional registries that supply very valid information. However, this information does not always agree with that expressed in the large registries since they take ethnic and environment characteristics of each region into account.

Immunosuppression is the main risk factor for the development of short and long-term neoplasms after transplantation of any organ. However, some authors do not admit this etiopathogenic association for all the cancer types that the renal transplant recipients may develop [13]. Each organ has some epidemiological characteristics for development of post-transplant neoplasms. Specifically in the renal transplant, it is known that neoplasms are more frequent in the patient receiving dialysis than in the age-matched general population [5], [14]. On the one hand, in some patients, cancer is the cause of renal failure as, for example, patients with multiple myeloma or with surgically treated renal or urinary tract neoplasms. On the other hand, analgesic nephropathy, a known cause of end stage renal disease, is associated with a greater risk of renal cancer [15]. And finally, patients who remain on dialysis for a long time frequently acquire a cystic disease in their non-functioning native kidneys, that is associated with a higher incidence of renal carcinoma [14], [16].

Furthermore, renal donor and recipient characteristics have been changing in recent years. Renal transplant recipient and cadaveric donor age is increasing [17]; thus, cancer prevalence in the older recipients as well as danger of transmission of unnoticed neoplasm from older donors will be higher.

We are going to divide this exposition into three classical sections to describe the epidemiology of neoplasms in renal transplant: (1) renal transplant candidates with cancer; (2) tumors transmitted from the organ donor; (3) de novo neoplasms in the renal transplant recipient. In this latter section, we will distinguish early appearing and late appearing neoplasms.

Section snippets

Renal transplant candidates with neoplasm

In a retrospective study, Penn [18], [19] observed that after renal transplant, recurrence of previously existing and treated neoplasms in the recipients was 22%. A total of 54% of the recurrences were cancers treated in the two pre-transplant years, 33% in those treated 2–5 years before and only 13% in those treated more than 5 years before.

Table 1, Table 2 summarize the recurrence incidence of pre-existing tumors in the recipient before the renal transplant and waiting times recommended

Donor transmitted cancer

Any background of malignant neoplasm in donors should be an absolute contraindication to the donation of their organs. However, the scarcity of organs for transplant and the long waiting lists for transplant have led to the consideration of donors with central nervous system (CNS) cancers that only rarely metastasize as well as donors with background of cured neoplasm and donors with in situ cancers discovered when the organs are procured. Some of these organs have been transplanted after the

De novo neoplasms after renal transplant

According to the CTTR, the most prevalent de novo neoplasms in organ transplant recipients are skin cancers and post-transplant lymphoproliferative disease (PTLD). Cutaneous neoplasms predominate in the renal recipient on the contrary to in the non-renal organ recipient in which the most prevalent neoplasms are the PTLD [4] (Table 8). This different distribution of the de novo neoplasms in renal and non-renal transplant recipients may be explained by the greater follow-up time and the lower

Dr. Amado Andrés carried out his medical studies in the “Autónoma” University of Madrid, graduating in 1981. Later, he studied the nephrology speciality in the Hospital 12 de Octubre of Madrid and obtained his PhD in Medicine in 1992. Since 1988, he has been working in renal transplant area in the nephrology department of the Hospital 12 de Octubre. Since 1989, he has been the general transplant coordinator in the Hospital 12 de Octubre. He has published more than 200 articles in journals and

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    Dr. Amado Andrés carried out his medical studies in the “Autónoma” University of Madrid, graduating in 1981. Later, he studied the nephrology speciality in the Hospital 12 de Octubre of Madrid and obtained his PhD in Medicine in 1992. Since 1988, he has been working in renal transplant area in the nephrology department of the Hospital 12 de Octubre. Since 1989, he has been the general transplant coordinator in the Hospital 12 de Octubre. He has published more than 200 articles in journals and books on his speciality. His research lines are focused on the study of expanded donor pool, older donors kidney transplant and management of several immunosuppressive therapies. He has directed several research projects on these issues as well as some doctorate thesis.

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