Cancer after kidney transplantation

Cancer is a major cause of mortality and morbidity after transplantation. The overall risk of cancer among transplant recipients is at least 2.5–3-fold greater than that of the age- and gender-matched general population. The increased risk is also type specific, and is greatest among virus-related neoplasms such as Kaposi sarcoma, post-transplant lymphoproliferative disease, and vulvovaginal cancers, with an excess risk of at least 9–20 times greater than that of the general population. Cancer prognoses are also poor in transplant recipients, with less than 10% surviving 5 years after initial diagnoses. Despite the increased cancer risk, little is known about the efficacy of treatment, the screening strategies, and the outcomes of patients with cancer and kidney transplants. Uncertainties also exist as to how the various types of modern immunosuppression impact on recipients’ overall long-term survival and quality of life. This chapter discusses the incidence and prognoses of patients with de novo cancer after transplantation, the epidemiology of donor cancer transmission, the outcomes of transplanting patients with a prior history of cancer, as well as the different approaches to cancer screening and management after kidney transplantation.

Overall and Site-Specific Cancer Mortality in Patients on Dialysis and after Kidney Transplant

Journal of the American Society of Nephrology ◽

10.1681/asn.2018090906 ◽

2019 ◽

Vol 30 (3) ◽

pp. 471-480 ◽

Cited By ~ 25

Author(s):

Eric H. Au ◽

Jeremy R. Chapman ◽

Jonathan C. Craig ◽

Wai H. Lim ◽

Armando Teixeira-Pinto ◽

...

Keyword(s):

General Population ◽

Kidney Cancer ◽

Cancer Mortality ◽

De Novo ◽

Cancer Death ◽

Transplant Recipients ◽

Non Hodgkin Lymphoma ◽

Increased Risk ◽

Standardized Mortality Ratios ◽

Background Patients with ESRD have a substantially increased cancer risk, but few studies have examined the patterns of cancer mortality along a patient's journey from dialysis to transplantation.MethodsWe identified all Australian patients on dialysis and patients with transplants from 1980 to 2014 from the Australia and New Zealand Dialysis and Transplant Registry. Using standardized mortality ratios (SMRs), we compared cancer mortality among patients on dialysis and patients with transplants versus the general population (overall and by age, sex, year, and site); we also performed a subgroup analysis excluding patients with preexisting cancers.ResultsWe followed 52,936 patients on dialysis and 16,820 transplant recipients for 170,055 and 128,352 patient-years, respectively. There were 2739 cancer deaths among patients on dialysis and 923 cancer deaths among transplant recipients. Overall, cancer SMRs were 2.6 for patients on dialysis and 2.7 for transplant recipients. For patients on dialysis, SMRs were highest for multiple myeloma (30.5), testicular cancer (17.0), and kidney cancer (12.5); for transplant recipients, SMRs were highest for non-Hodgkin lymphoma (10.7), kidney cancer (7.8), and melanoma (5.8). Some 61.0% of patients on dialysis and 9.6% of transplant recipients who experienced cancer death had preexisting cancer. The SMRs for de novo cancer was 1.2 for patients on dialysis and 2.6 for transplant recipients.ConclusionsPatients on dialysis and transplant recipients experienced >2.5-fold increased risk of cancer death compared with the general population. This increased risk was largely driven by preexisting cancers in patients on dialysis and de novo cancers in patients with transplants.

Post-transplant cancer: An epidemiological evaluation

Journal of Onco-Nephrology ◽

10.1177/2399369320953869 ◽

2020 ◽

Vol 4 (3) ◽

pp. 145-152

Author(s):

Anna Francis ◽

Eric Au ◽

Wai H Lim ◽

Germaine Wong

Keyword(s):

General Population ◽

Lymphoproliferative Disease ◽

Excess Risk ◽

Current Evidence ◽

Solid Organ ◽

Transplant Recipients ◽

Post Transplant ◽

Risk Of Death ◽

Increased Risk ◽

Kidney transplantation is a lifechanging event for patients with end-stage kidney disease (ESKD) because it improves the quality of life and survival of these patients. However, it is not a cure and is not without complications. Transplant recipients have an excess risk of premature death (largely from cancer and cardiovascular disease (CVD)) by at least 10-times compared to the general population. Published work has identified cancer as one of the most important and feared outcomes in transplant recipients and is a key research priority recognised by both patients and health professionals. There is also convincing epidemiological evidence, suggesting the overall risk of developing cancer in the transplant population is approximately 2 to 3-fold higher compared to the age-matched general population. Unlike CVD, where the death rates have fallen considerably over the past decade in this population in response to better screening, preventative and intervention approaches, the excess risk of cancer-related deaths in transplant recipients remains at least 10-fold higher compared to cancer patients in the general population. The causes of the increased risk of death are unknown but may be a consequence of possible differences in tumour biology under the influence of immunosuppression. In this review, we will discuss the epidemiology of overall and site-specific cancer risk and death across different countries. We will also focus on the current evidence on the prevention and screening in our at-risk transplant candidates. Finally, management strategies of common cancers such as skin, post-transplant lymphoproliferative disease and solid organ cancers such as colorectal, breast and lung cancer will be evaluated.

De Novo Cancer Incidence after Kidney Transplantation in South Korea from 2002 to 2017

Journal of Clinical Medicine ◽

10.3390/jcm10163530 ◽

2021 ◽

Vol 10 (16) ◽

pp. 3530

Author(s):

Boyeon Kim ◽

Minjin Kang ◽

Yoonjung Kim ◽

Hyung Soon Lee ◽

Banseok Kim ◽

...

Keyword(s):

Kidney Transplantation ◽

South Korea ◽

Cancer Incidence ◽

Proportional Hazards ◽

De Novo ◽

Cancer Development ◽

National Database ◽

Monitoring Methods ◽

Increased Risk ◽

Advances in patient care and immunosuppressive drugs have improved graft survival, resulting in an increase in kidney transplantation (KT); however, persistent immunosuppression is thought to cause late occurrence of cancer. This population-based study consisted of a total of 14,842 patients whose data from the years 2002 to 2017 were collected from the National Health Information Database in South Korea. Malignancies occurred in 7.6% of the total KT patients. Prostate and thyroid cancers were the most common in males and females, respectively. From the age-adjusted incidence analysis, Kaposi’s sarcoma showed the highest standardized incidence ratio in both male and female patients. According to the linear regression model, cancer incidence in KT recipients under immunosuppressive conditions increased by approximately 0.1% each month. Patients’ age over 39 and the use of prednisolone as an initial steroid regimen were associated with increased risk of cancer development after KT. Our regression and proportional hazards models will help clinicians to predict the approximate cancer incidence risk when monitoring KT recipients. Based on the largest available national database, screening or monitoring methods for cancer detection and prevention can be established for KT patients by considering the factors involved in cancer development.

Cancer and mTOR inhibitors in kidney transplantation recipients

PeerJ ◽

10.7717/peerj.5864 ◽

2018 ◽

Vol 6 ◽

pp. e5864

Author(s):

Chih-Chin Kao ◽

Jia-Sin Liu ◽

Yu-Kang Chang ◽

Ming-Huang Lin ◽

Yen-Chung Lin ◽

...

Keyword(s):

Kidney Transplantation ◽

De Novo ◽

Mtor Inhibitors ◽

Cancer Development ◽

Cumulative Exposure ◽

National Database ◽

Risk Of Death ◽

Increased Risk ◽

De Novo Cancer ◽

Background Previous studies show that mTOR inhibitors decrease the risk of cancer development after kidney transplantation. However, the effect of cumulative doses of mTOR inhibitors on cancer after kidney transplantation is not well known. Methods In the current study, patients were registered into a national database in Taiwan. Between year 2000 and 2013, 4,563 patients received kidney transplantation. They were divided into two groups, according to mTOR inhibitors usage. The cumulative dose of mTOR inhibitors was recorded. Patients were followed-up until de novo cancer development, death, or the end of 2014. Results Patients were divided into two groups: mTOR inhibitors users (study group, n = 828) and mTOR inhibitors non-users (control group, n = 3,735). The median follow-up duration was 7.8 years. The risk of de novo cancer (hazards ratio (HR) 0.80, 95% CI [0.60–1.09], p = 0.16) and risk of death (HR 1.14, 95% CI [0.82–1.60], p = 0.43) was not different between mTOR inhibitor user and non-user groups. Neither high- nor low-dose exposure to mTOR inhibitors was associated with increased risk of cancer or mortality. Analysis of cancer subtypes showed no influence by mTOR inhibitors. In addition, the cause of mortality was not significantly different between the two groups. Discussion We could not find the association of mTOR inhibitors use and risk of de novo cancer development or mortality in patients with kidney transplantation in Chinese patients. Cumulative exposure to mTOR inhibitors did not change the results.

Cardiovascular calcifications in kidney transplant recipients

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab053 ◽

2021 ◽

Author(s):

Manuel Alfredo Podestà ◽

David Cucchiari ◽

Paola Ciceri ◽

Piergiorgio Messa ◽

José-Vicente Torregrosa ◽

...

Keyword(s):

Kidney Transplantation ◽

Kidney Transplant ◽

De Novo ◽

Immunosuppressive Drugs ◽

Current Evidence ◽

Transplant Recipients ◽

Increased Risk ◽

Cardiovascular Calcifications

AbstractVascular and valvular calcifications are highly prevalent in kidney transplant recipients (KTRs) and are associated with an increased risk of cardiovascular events, which represent the leading cause of long-term mortality in these patients. However, cardiovascular calcification has been traditionally considered as a condition mostly associated with advanced chronic kidney disease stages and dialysis, and comparatively fewer studies have assessed its impact after kidney transplantation. Despite partial or complete resolution of uraemia-associated metabolic derangements, KTRs are still exposed to several pro-calcifying stimuli that favour the progression of pre-existing vascular calcifications or their de novo development. Traditional risk factors, bone mineral disorders, inflammation, immunosuppressive drugs and deficiency of calcification inhibitors may all play a role, and strategies to correct or minimize their effects are urgently needed. The aim of this work is to provide an overview of established and putative mediators involved in the pathogenesis of cardiovascular calcification in kidney transplantation, and to describe the clinical and radiological features of these forms. We also discuss current evidence on preventive strategies to delay the progression of cardiovascular calcifications in KTRs, as well as novel therapeutic candidates to potentially prevent their long-term deleterious effects.

De Novo Malignancies after Kidney Transplantation

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.14570920 ◽

2021 ◽

pp. CJN.14570920

Author(s):

David Al-Adra ◽

Talal Al-Qaoud ◽

Kevin Fowler ◽

Germaine Wong

Keyword(s):

Kidney Transplantation ◽

De Novo ◽

Treatment Strategies ◽

Lymphoproliferative Disease ◽

High Risk Population ◽

Kidney Transplants ◽

Optimal Care ◽

Living With Cancer ◽

Risk Of Cancer ◽

Age And Sex

Cancer is an important outcome after kidney transplantation because it is the second leading cause of death in most Western countries. The excess risk of cancer after transplantation is approximately two to three times higher than the age- and sex-matched general population, driven largely by viral- and immune-related cancers. Once cancer develops, outcomes are generally poor, particularly for those with melanoma, renal cell carcinoma, and post-transplant lymphoproliferative disease. More importantly, effective screening and treatment strategies are limited in this high-risk population. In this review, we begin with a patient’s journey that maps the experience of living with a kidney transplant and understand the patient’s knowledge, education, and experience of cancer in the context of transplantation. The epidemiology and burden of cancer in recipients of kidney transplants, along with the up-to-date screening and treatment strategies, are discussed. We also focus on the current understanding of optimal care for recipients of kidney transplants who are living with cancer from the patients’ perspectives.

De Novo Cancers Arising in Organ Transplant Recipients are Associated With Adverse Outcomes Compared With the General Population

Transplantation Journal ◽

10.1097/tp.0b013e3181a238f6 ◽

2009 ◽

Vol 87 (9) ◽

pp. 1347-1359 ◽

Cited By ~ 110

Author(s):

Yun Miao ◽

Jason J. Everly ◽

Thomas G. Gross ◽

Amit D. Tevar ◽

M Roy First ◽

...

Keyword(s):

General Population ◽

De Novo ◽

Organ Transplant ◽

Adverse Outcomes ◽

Transplant Recipients ◽

Organ Transplant Recipients

Correlation of Prolonged Total Ischemic Time with Body Mass Index in Kidney Transplant: A Single Center Report

BioScientia Medicina ◽

10.32539/bsm.v5i11.367 ◽

2021 ◽

Vol 5 (11) ◽

pp. 1009-1013

Author(s):

Eriawan Agung Nugroho ◽

Erwin Wibowo ◽

Prathita Amanda Aryani

Keyword(s):

Body Mass Index ◽

Kidney Transplantation ◽

Kidney Transplant ◽

Body Mass ◽

The Body ◽

Health Concern ◽

Transplant Recipients ◽

Ischemic Time ◽

Increased Risk

Background: Chronic kidney disease (CKD) is a rising health concern worldwide, especially in Indonesia. The treatment of choice for end-stage renal disease is Kidney Transplantation.1 Numerous studies showed that prolonged total ischemic ischemic time may cause hypoxia of the graft tissue and increased risk of ischemia and reperfusion injury (IRI) and delayed graft function (DGF).2 Body mass index of kidney transplant recipients may cause prolonged duration of the procedure, as well as prolonged total ischemic time. This study aimed to determine the correlation between prolonged total ischemic time with body mass index. Method: This was an observational and cross-sectional analysis at Kariadi General Hospital Semarang involving patients who underwent kidney transplantation from January 2016 to December 2019. The total ischemic time was recorded intraoperatively. The Body Mass Index data were provided by medical records. The program used to statistically analyze the data was SPSS 23.0, and Spearman was used for hypothesis testing. Result: This study included 25 kidney transplant recipients. The mean total ischemic time was 43,27 ± 6,63 minutes. There was a significant positive correlation between prolonged ischemic time and body mass index (r= 0,506 ; p= 0,010). Conclusion: Prolonged total ischemic time was positively correlated with increased body mass index and these results are statistically significant.

Venous Thromboembolism and the Risk of Death and Graft Loss in Kidney Transplant Recipients

American Journal of Nephrology ◽

10.1159/000480304 ◽

2017 ◽

Vol 46 (4) ◽

pp. 343-354 ◽

Cited By ~ 6

Author(s):

Ngan N. Lam ◽

Amit X. Garg ◽

Greg A. Knoll ◽

S. Joseph Kim ◽

Krista L. Lentine ◽

...

Keyword(s):

Retrospective Study ◽

Venous Thromboembolism ◽

General Population ◽

Kidney Transplant ◽

Graft Loss ◽

Transplant Recipients ◽

Risk Of Death ◽

Increased Risk

Background: The implications of venous thromboembolism (VTE) for morbidity and mortality in kidney transplant recipients are not well described. Methods: We conducted a retrospective study using linked healthcare databases in Ontario, Canada to determine the risk and complications of VTE in kidney transplant recipients from 2003 to 2013. We compared the incidence rate of VTE in recipients (n = 4,343) and a matched (1:4) sample of the general population (n = 17,372). For recipients with evidence of a VTE posttransplant, we compared adverse clinical outcomes (death, graft loss) to matched (1:2) recipients without evidence of a VTE posttransplant. Results: During a median follow-up of 5.2 years, 388 (8.9%) recipients developed a VTE compared to 254 (1.5%) in the matched general population (16.3 vs. 2.4 events per 1,000 person-years; hazard ratio [HR] 7.1, 95% CI 6.0-8.4; p < 0.0001). Recipients who experienced a posttransplant VTE had a higher risk of death (28.5 vs. 11.2%; HR 4.1, 95% CI 2.9-5.8; p < 0.0001) and death-censored graft loss (13.1 vs. 7.5%; HR 2.3, 95% CI 1.4-3.6; p = 0.0006) compared to matched recipients who did not experience a posttransplant VTE. Conclusions: Kidney transplant recipients have a sevenfold higher risk of VTE compared to the general population with VTE conferring an increased risk of death and graft loss.

P1761SIDE EFFECTS OF MTOR INHIBITORS DEPEND ON THE BASELINE METABOLIC STATUS OF KIDNEY TRANSPLANT RECIPIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1761 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

David Cucchiari ◽

Alicia Molina-Andujar ◽

Enrique Montagud-Marrahi ◽

Jordi Rovira ◽

Fritz Diekmann

Keyword(s):

Kidney Transplantation ◽

Side Effects ◽

Kidney Transplant ◽

De Novo ◽

Mtor Inhibitors ◽

Metabolic Status ◽

Transplant Recipients ◽

Post Hoc Analysis ◽

Post Hoc

Abstract Background and Aims Biologically, the cellular activity of the mTOR complexes depends on the balance between the catabolic and the anabolic inputs. Hence, we hypothesized that the metabolic side effects of mTOR inhibitors (mTORi) in kidney transplantation depend on the baseline metabolic status of the patient. Method The analysis included all the patients that have been transplanted in our Center between June 2013 to December 2016, completed one year of follow-up and did not change medication during the first year after kidney transplantation (per-protocol population, n=298). Outcomes chosen include de novo diabetes, 1-year difference from baseline in glycated hemoglobin (HbA1c), triglycerides and total cholesterol. Kidney transplant recipients were treated either with an mTORi (either Sirolimus or Everolimus, n=134) or Mycophenolic Acid (MPA, n=164). Both drugs were always accompanied by tacrolimus and steroids. Patients were stratified according to the treatment received (mTORi versus MPA) and the baseline metabolic status (diabetes mellitus type 2 and obesity). Differences among groups were analyzed with exact Fisher test and ANOVA test with LSD post-hoc analysis. Results We observed a strong difference for 1-year change in HbA1c depending on the baseline metabolic status of the patients (P<0.001 between groups, Figure 1a). The worst results were observed for patients with baseline diabetes. Among these, obese patients treated with mTORi had the higher increase in HbA1c (3.04 ± 1.18% from baseline, P<0.01 with all groups at post-hoc analysis). De-novo diabetes was more frequent in patients taking mTORi (23.4 vs. 13.1%), albeit not significantly (P=0.100) and without differences taking into account obesity as a covariate. Triglycerides increased substantially in patients without baseline diabetes and treated with mTORi (P<0.05). Surprisingly, in diabetic patients no differences were observed in triglycerides between mTORi and MPA groups (Figure 1b). There were no differences in the increase in total cholesterol among groups (P=0.155) (Figure 1c). Conclusion We observed that the 1-year increase in HbA1c and triglycerides attributable to mTORi after kidney transplantation depends on the baseline metabolic status of the patients. We propose that the metabolic side effects of mTORi depend on the balance between anabolic and catabolic inputs of every kidney transplant recipient.