2 Clinical need and practice
2.1 End-stage renal disease, or established renal failure, is defined as an irreversible decline in kidney function that is severe enough to be fatal without renal replacement therapy. The most common causes of chronic renal damage leading to established renal failure are diabetes mellitus, arteriosclerosis, hypertension, glomerulonephritis and microscopic vasculitis. Acute renal failure from traumatic injury or infection may also lead to established renal failure. In children, it is usually caused by congenital structural abnormalities, but may be genetic or the result of glomerulonephritis.
2.2 People with established renal failure can become tired and nauseated and lose their appetite, leading to weight loss. Pruritus may also occur. Signs of established renal failure include fluid retention, pallor and raised blood pressure, which are accompanied by lowered haemoglobin levels and abnormal levels of biochemical markers. Established renal failure leads to death unless renal replacement therapy is provided, through haemodialysis, peritoneal dialysis or a kidney transplant.
2.3 In the UK in 2005 there were 41,776 adults and 748 children (younger than 18 years) on renal replacement therapy. This is a 28% increase in patient numbers since 2000. In the UK in 2005, the median age at which people started renal replacement therapy was 65 years. Survival in the 1st year after starting renal replacement therapy for all patients regardless of age was 79%. Five-year survival rates varied depending on age. In people aged 18–34 years 58% were alive 5 years after starting renal replacement therapy, and 12% in people aged 75 years or older.
2.4 Kidney transplantation, which involves implanting a kidney from a donor, is the preferred therapeutic option where it is possible. Kidneys for transplantation may come from living donors or deceased organ donors. Deceased organ donors may be certified as dead either by brainstem criteria (deceased heart-beating donors) or after cardiac arrest (non-heart-beating donors). The availability of kidneys from deceased heart-beating donors has decreased by about 20% in the last decade. Kidneys from deceased heart-beating donors are allocated nationally; kidneys from non-heart-beating donors are allocated locally.
2.5 Non-heart-beating donors are categorised according to the Maastricht criteria, and described as controlled (where cardiac death is expected, but the criteria for brainstem death are not fulfilled) or uncontrolled (where cardiac death is unexpected). Kidneys from non-heart-beating donors (particularly those categorised as uncontrolled) may have long periods of warm ischaemic time, that is, the time that the organ spends deprived of oxygen before it is cooled and retrieved. As a result, kidneys from non-heart-beating donors can have higher rates of delayed graft function (the graft does not function immediately) or primary non-function (the graft never functions) than those from heart-beating donors. Primary non-function and early graft failure are associated with an increased risk of death in the ensuing months. Kidney function is also affected by cold ischaemic time (the duration of storage in cold conditions between retrieval and transplantation), but cooling the organ reduces the metabolic rate and thereby decreases the rate of damage to the organs compared with warm ischaemia.
2.6 Kidneys from 'extended criteria' deceased heart-beating donors may also be used to expand the donor pool. These are kidneys from donors who are aged over 60 years, or are over 50 years and have two or more of: a history of hypertension, a history of cerebral vascular accident, or terminal creatinine levels greater than 133 micromoles/litre. Like kidneys from non-heart-beating donors, kidneys from extended criteria donors are also associated with higher rates of delayed graft function and primary non-function than those from non-extended criteria donors.
2.7 Successful kidney transplantation removes the need for dialysis, but immunosuppressant drugs are needed permanently to prevent rejection of the graft. Complications of immunosuppression include increased risk of infections and malignancy, especially skin cancer and lymphoproliferative disorders. Nephrotoxicity is a particular complication of some immunosuppressive regimens. Post-transplantation diabetes mellitus is a potentially serious side-effect of treatment. Other treatment side-effects, depending on the drugs used, may include hirsutism, alopecia, tremors, mood swings or gastrointestinal intolerance.
2.8 In the UK in 2005, 76% of people accepted for renal replacement therapy started treatment with haemodialysis and 21% started treatment with peritoneal dialysis. Only 3% of patients received a kidney transplant before they started dialysis. There is increasing demand for kidney transplants; the waiting list has increased by 48% since 1998. Demand for kidneys outstrips supply. In the UK in 2006, 1403 kidneys from deceased donors were transplanted (from 765 deceased kidney donors); 6384 people were awaiting transplantation. Therefore, there is a need to increase kidney donation and to make donated kidneys function in the best possible way.