The action of transplanting an organ initiates an inflammatory response, a process which can lead to organ rejection. Once the donor blood supply is cut off from the organ, tissue ischaemia ensues: hypoxic conditions deplete cells of ATP which leads to cell death and inflammatory mediator release. Although revascularisation is crucial for salvaging the organ, reperfusion itself can cause tissue damage both locally and systemically. So-called ‘marginal’ organs are at a higher risk of IRI, as they are sourced from an extended donor pool. For example, the donor may be elderly or have significant co-morbidities.

Hyperacute rejection occurs almost immediately following transplantation resulting in swelling and discoloration of the donor organ, which is catastrophic for the patient. It is due to pre-formed cytotoxic antibodies present in the host, specific for donor antigens. Fortunately, hyperacute rejection is rare owing to careful cross-matching.

Acute rejection arises in as many as 50 % of grafts less than six months post-transplant and is characterised by a T-cell response, accompanied by a number of inflammatory mediators such as tumour necrosis factor-alpha (TNFα), interferon-gamma (IFNγ) and interleukin-2 (IL-2).

A T-cell-mediated response can only take place if the T-cell has received two signals: signal one occurs at the T-cell receptor interaction with antigen, which is presented by MHC on antigen-presenting cells (APC) (Fig. 25.1). Signal two is provided by co-stimulatory molecules on the APC, which bind to various complimentary molecules on the T-cell surface. If signal one occurs in the absence of signal two T-cell anergy, or unresponsiveness, ensues (i.e. no immune response). However, if co-stimulatory cell-cell interactions occur between the T-cell and the APC (signal two), then a full T-cell response is initiated. This two signal model is significant in the development of new anti-rejection medications (see below).

Chronic rejection occurs more than six months post-transplant. Contributing features include antibody release by plasma cells that ultimately destroy the graft, and as such is an irreversible process. Usually the result of vascular occlusion, chronic rejection is characterised by antibody responses to vascular endothelial cells and the subsequent response of these cells, such as smooth muscle proliferation and interstitial scarring.

To prevent organ rejection, transplant recipients are placed on anti-rejection medication, or immunosuppression. Unfortunately, there are no specific methods to prevent an immune response which is directed only to the grafted organ, meaning a non-specific dampening of the entire immune system is required.

In 2013/14, 3032 kidney transplants took place in the UK while 5881 patients were on the waiting list [9].

Kidney transplants are usually indicated in end-stage renal disease (eGFR < 15 mL/min), with common causes including:

Dialysis is offered at this stage but is only a short-term, non-curative solution. Ultimately, patients will require a transplant, which offers the best chance of long-term survival. Most studies demonstrate significantly lower mortality in kidney transplant recipients, compared with haemodialysis patients [11]. In addition, the quality of life of kidney transplant recipients is significantly superior. Absolute contraindications include active infection and malignancy, whereas relative contraindications include patient age and other significant co-morbidities.