Analysing, predicting and improving outcomes for kidney transplant recipients

Abstract

Kidney failure is a growing global health burden. Kidney transplantation offers the best treatment for eligible patients, however long-term outcomes remain suboptimal due to chronic rejection and premature death, particularly from cardiovascular disease, infection, and cancer. As the transplant population becomes older, more obese, and more comorbid, understanding how these factors influence outcomes is important. Clinical registries and non-inferiority trials are increasingly relied upon to support research and guide policy. This thesis evaluates the reliability of registry data, the impact of evolving transplant population characteristics on outcomes, and the quality of evidence from non-inferiority trials. Deterministic linkage between ANZDATA and the A2309 clinical trial showed excellent agreement for key variables. In recipients aged ≥70 years, transplantation provided a survival benefit beyond 9 months compared to remaining on dialysis. Among 1,522 paired deceased-donor transplants, obesity was associated with higher risks of delayed graft function, graft failure, and death. In 65,712 kidney failure patients, obesity was linked to lower cancer incidence and mortality, with site-specific variation. The systematic review of 44 non-inferiority trials in kidney transplantation identified substantial deficiencies in trial design and reporting, including inadequate justification of non-inferiority margins, inappropriate use of risk measures, poor handling of missing data, and frequent misinterpretation of results. Overall, the ANZDATA Registry provides reliable data for outcome evaluation. Transplantation benefits selected elderly patients despite early risk, while obesity presents complex effects on graft and cancer outcomes. The major deficiencies in non-inferiority trial design and reporting highlight an urgent need for stricter editorial standards, better trialist awareness, and stronger guideline adherence to improve the quality of evidence in our field.