Malignancy in Chinese end-stage renal disease patients before and after kidney transplantation

Abstract

Although cardiovascular disease and infection remain the most common causes of death in patients suffering from end-stage renal disease (ESRD), malignancies are now increasing as a cause of death among these patients. In my studies, the risks of all cancers were shown to be elevated in both Chinese chronic dialysis and kidney transplant patients. The standardized incidence ratios (SIR)s of dialysis patients and transplant recipients were 1.44 and 2.94 respectively. Kidney cancer had the highest SIR in dialysis patients while non-Hodgkin lymphoma had the highest SIR in transplant recipients. Similar increase in cancer mortality was also shown in kidney transplant recipients, especially with certain types of cancers. However, an elevated standardized mortality ratio (SMR) could not be demonstrated in dialysis patients except for kidney cancer. Similar to most regions of the developed world, diabetic nephropathy (DN) was the most common etiology leading to ESRD in Hong Kong, and was found to be associated with increased incidence of cancers of colorectum, liver and larynx in my study. The development of cancers in patients with ESRD can be multifactorial. Long-term immunosuppression is an important contributor to the increased number of posttransplant cancers in kidney transplant recipients. The ultimate aim of immunosuppression is to minimize the risk of acute rejection without increasing the incidence of malignancy and other complications. Calcineurin inhibitors (CNIs), namely cyclosporine and tacrolimus, are commonly used in kidney transplant recipients. In my prospective, randomized and paired kidney study, tacrolimus-treated patients had a lower incidence of acute rejection and better long-term renal function when compared with cyclosporine-treated patients. At the same time, the incidence of malignancies was comparable between both groups of patients. On the other hand, it remains unclear how immunosuppression should be adjusted for patients who developed posttransplant cancers. My retrospective study shows that the use of mammalian target of rapamycin inhibitors together with CNI minimization could be a reasonable option in these patients in view of the relatively stable renal function, very low rejection rate and low cancer recurrence rate. Besides adjustment of immunosuppression, cancer surveillance can also play a significant role in reducing the cancer burden in kidney transplant recipients. I demonstrated that half of the patients with renal cell carcinoma (RCC) had acquired cystic kidney disease (ACKD) and the prognosis of patients was better if RCC could be detected early. Thus we should consider screening all kidney transplant recipients for ACKD and RCC regularly. Furthermore, I found that all Chinese kidney transplant recipeints with hepatocellular carcinoma (HCC) had chronic viral hepatitis and the presence of chronic HBV infection was associated with a 78-fold higher relative risk for HCC. Hence, regular HCC surveillance in all Chinese HBV kidney transplant recipients is highly recommended. In conclusion, this series of studies can allow us to have a better understanding of cancer risk and the various modifiable risk factors in Chinese ESRD patients which are important for improvement of clinical outcome in these patients.