NOMINATE/ Minimisation of Immunosuppression in Kidney Transplantation
Status:
Not yet recruiting
Trial end date:
2027-02-20
Target enrollment:
Participant gender:
Summary
Kidney transplantation provides the optimal form of kidney replacement therapy for the
majority of people with end-stage kidney disease, and has now become the commonest form of
kidney replacement therapy. However, donor and recipient demographics have changed
considerably over the past few decades: increasingly older donor kidneys are transplanted
into progressively older recipients with greater comorbidities. Increasing age remains a
major risk factor for death after kidney transplantation, with the commonest causes of deaths
for recipients aged 70 and over being cardiovascular, infection, and malignancies.
Immunosuppressant drugs which are critical for the maintenance of the transplanted organ can
contribute to increased morbidity and mortality, by direct effects or through lowered
immunity predisposing to infection. Cytomegalovirus (CMV) is one of the most common
opportunistic infections that affects renal transplant patient outcome and can be monitored
prospectively. Hence, minimising immunosuppression, especially in older recipients, may
result in better graft and patient outcomes as many side-effects are dose dependant. However,
to date drug doses have never been adjusted based on age, despite significant changes that
occur to immune responsiveness as patients grow older. In addition , researchers have not had
a biomarker to help define appropriate immunosuppressive levels for each individual.
The investigators therefore aim to study the effect of reducing the target immunosuppression
drug levels( of tacrolimus and mycophenolate) in kidney transplant recipients >60 years,
using CMV viraemia as a main outcome measure, and investigating rates of rejection and
development of de novo donor-specific anti-HLA antibodies. The investigators will assess the
clinical utility of donor-derived cell free DNA (dd-cfDNA) as a means to guide
immunosuppression minimisation. The investigators propose that the use of lower doses of
immunosuppression will result in fewer infection-related complications, translating to
improved patient outcomes. The research will be carried out in kidney transplant centres
where prospective CMV monitoring is practiced.