Although modern immunologic assessments and potent immunosuppression markedly decreased the acute rejection rate in KT, it fails to suppress chronic rejection due to immunologic and non-immunologic factors; this has becomes a major obstacle for long-term graft survival. Furthermore, as both graft and patient survival improve, KT patients, who are often in the early stages of CKD, become exposed to chronic immunosuppression. Therefore, KT patients can develop many medical complications such as cardiovascular events, metabolic complications, infection, malignancy, and mineral bone disorders as well as chronic rejection. Indeed, chronic medical complications have become a major cause of morbidity and mortality in KT patients.
Antibody-mediated injury is an important cause of immunologic injury in chronic rejection or chronic allograft nephropathy. Because noncompliance is one of main causes of antibody formation, compliance monitoring together with antibody monitoring is included in our prospective study. Hypertension, hyperlipidemia, and diabetes, so called non-immunologic risk factors for chronic allograft nephropathy, are common after KT and are reported to induce chronic damage to allografts.
The nonimmunologic risk factors for chronic allograft nephropathy are among traditional risk factors for cardiovascular disease. Cardiovascular events have been reported to be the most common cause of death in KT patients in Western countries. However, many studies show that racial/ethnic disparities exist in mortality and cardiovascular outcome among CKD patients [18–21]. Transplant outcomes seem to differ according to racial differences [22, 23]. Asian KT patients generally have better renal allograft survival and a lower burden of cardiovascular disease than other racial groups. The KNOW-KT, the first large-scale cohort study in Asian KT patients, aims to explore allograft survival rate, cardiovascular events, and metabolic profiles and to investigate the risk factors in Asian or Korean KT patients.
Risk for malignancy is higher in CKD patients than in the general population . Moreover, the risk for malignancy is higher in KT patients than in CKD patients due to chronic immunosuppression. The relative prevalence of common malignancy differs according to region. For example, gastric and hepatic cancers are the most common types of cancer in Korea, whereas they are not as common in Western countries. Therefore, malignancy patterns in KT patients could differ between Asian and Western countries. Infectious complications are also one of the main complications after transplantation. There may be differences in immunosuppressive protocols or prophylaxis policy due to differences in health insurance coverage or disease prevalence. These potential differences could result in different patterns of infection in Korean KT patients. Analysis of local infection profiles can help in redirecting prophylactic policy for KT patients in a specific country.
The KNOW-KT will evaluate the complication profiles of mineral-bone disorders across various renal functions. The KNOW-KT will also evaluate the socio-economic burden and impact on the quality of life. Comparison of the KNOW-KT with other large-scale KT cohorts through international collaboration may provide a platform for future research.
Various biomarkers from the serum and urine samples will be explored for the risk prediction of adverse consequences. Genetic and epigenetic factors will be sought. Interaction between donor factors and recipient factors is a unique feature in transplant cohorts and cannot be seen in conventional CKD cohorts. Especially, analysis of bio-samples from both living donors and DDs together with recipient bio-samples could be one of the strengths of the present cohort study.
The Collaborative Transplant Study (CTS) based in Europe , the Scientific Registry of Transplant Recipients (SRTR) in USA , and the Australia and New Zealand Dialysis and Transplant (ANZDATA) registry are large-scale registries . All these large cohorts have strengths related to the large sample size and the fact that they are representative as nationwide database, whereas they also have limitations inherent to as registry data, such as simplicity of the outcome data and the heterogeneity of clinical follow-up data. They usually do not collect bio-samples that are matched with clinical data. However, the KNOW-KT clearly defined outcomes and carefully monitors study processes in order to meet predefined protocols and establish a bio-bank together with clinical data.
There are a few limitations in the KNOW-KT. First, the KNOW-KT will enroll a relatively small number of patients compared with the larger-scale registry database or the cohort studies in Western countries. Therefore, we should expand out cohort later in order to confirm some of the findings. Second, all routine laboratory and sampling procedures are processed in individual local transplant centers, although transport and storage of biospecimens are managed by a central laboratory. However, standards, laboratory methods, measurement units, and detection limits are generally consistent among these local laboratories; therefore, the discrepancies among procedures at individual laboratories will only have limited effects on the quality of collected data, if any. Third, we do not mandatorily collect kidney biopsy samples; instead, it depends on the policy of individual center. Nevertheless, the KNOW-KT is the first large-scale KT cohort study in Asian KT patients. Future larger-scale studies could confirm the major findings of this study.
As the first large-scale Asian KT cohort study to be performed longitudinally for up to 9 years, the KNOW-KT will help clarify the natural course, complication profiles, and the risk factors of the Asian KT population. Analyzing this cohort and comparing with other cohort studies in Western countries will provide information about the impact of race on transplant outcomes and a comprehensive insight into KT.