Posted by Mary E. on June 03, 1999 at 08:38:33:
Combined kidney and pancreatic transplantation
Ideal for patients with uncomplicated type 1 diabetes and chronic renal failure
Diabetes mellitus is the single most common cause of end stage renal failure in Western societies. Despite rigorous glycaemic control, dietary changes, exercise, and use of disease modifying drugs, some patients with diabetes, mostly but not exclusively those with type 1 disease, will develop renal failure requiring dialysis.1 In the first five years after transplantation, kidney graft survival is similar in diabetic and non-diabetic populations,2 but overall mortality in the diabetic group is three times that in non-diabetic transplant recipients.3 Accelerated coronary atherosclerosis, sudden death related to autonomic neuropathy, and infection account for much of this excess mortality. Strict control of blood glucose with intensive insulin therapy reduces, but does not eliminate, these risks.1 In the United States simultaneous kidney and pancreas transplantation is now regarded by many clinicians as the treatment of choice for uraemic diabetic patients in the absence of advanced coexisting vascular disease or after its correction.4-5 Is it time for the rest of the world to follow suit?
Since 1980 nearly 9000 pancreatic transplants have been performed worldwide,6 over two thirds of them in the United States; current trends suggest an annual rate exceeding 1500. In contrast, in the United Kingdom and elsewhere pancreatic transplantation has been viewed more critically. This concern has been fuelled by the high rate of surgical complications, with increased perioperative morbidity and mortality, and by the perceived risks associated with the requirement for increased immunosuppression to prevent organ rejection7: fewer than 200 patients have received pancreatic transplants in the United Kingdom.
The addition of a pancreatic transplant at the time of renal transplantation establishes a return to normal carbohydrate metabolism. 4 5 Quality of life is improved through the abolition of dietary restrictions, freedom from exogenous insulin and blood glucose monitoring, and removal of fear of hypoglycaemia. Combined kidney and pancreas transplantation produces patient and pancreatic graft survival rates of 92% and 79% at 1 year and 81% and 67% at 5 years, respectivelyresults comparable to cadaveric kidney transplantation in non-diabetic patients.2-6 Most importantly, early results show that not only does patient survival improve by at least 10% at five years but that long term kidney graft survival is also better after combined organ grafting than after renal transplantation and continued exogenous insulin.2-8 Moreover, when diabetic patients receive a kidney transplant histological changes of diabetic nephropathy recur within two years,9 progressing to end stage disease after 10 years. Successful pancreatic transplantation prevents recurrence of diabetic nephropathy in kidney grafts.
Careful patient selection is crucial as good results are achieved only in those who, at the time of transplantation, have not developed ischaemic heart disease, cerebrovascular disease, or major peripheral vascular disease. 4 5 Improvement, or at least stabilisation, of diabetic retinopathy, neuropathy, and vasculopathy is a further benefit of pancreatic transplantation, provided that irreversible ischaemic damage has not already occurred.5 The incidence of sudden death among patients with autonomic neuropathy is also reduced.
Advances in surgical practice and the development of effective immunosuppressive agents have contributed largely to the success of simultaneous kidney and pancreas transplantation. 10 11 The adoption of enteric drainage in preference to bladder drainage of pancreatic exocrine secretion has eliminated bladder and duodenal leaks, urethritis, and chemical cystitis and has reduced the incidence of recurrent acute pancreatitis, a common cause of graft loss. 10 11 Surgical practice has also evolved from systemic venous drainage of pancreas transplants via the iliac vein to portal venous drainage. This overcomes the problem of near hypoglycaemia experienced by some patients and avoids systemic hyperinsulinaemia, which has been linked to atherogenesis.10 Recently introduced immunosuppressive agents such as tacrolimus and mycophenolate mofetil have played an important part by substantially reducing graft losses due to rejection.10 The long term consequences of such immunosuppression, especially in relation to the risks of developing malignancy, remain to be clarified, but concerns about a high rate of infection having an impact on graft and patient survival appear to be overstated.12
Improved outcomes in simultaneous kidney and pancreas transplantation in diabetic patients with end stage renal failure warrant a reappraisal of the cautious approach so far adopted by many transplant centres outside the United States.
A Kumar, Senior registrar in renal medicine.
C G Newstead, Consultant renal physician.
J P A Lodge, Consultant transplant surgeon.
A M Davison, Professor of renal medicine.
Departments of Renal Medicine and Organ Transplantation, St James's University Hospital, Leeds LS9 7TF
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© British Medical Journal 1999