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Developments and dilemmas in renal transplantation
A H Wilkinson1, J T Rosenthal, G M Danovitch
1Department of Medicine, UCLA School of Medicine, USA.
Abstract:
The number of patients waiting for a kidney transplant is about three times greater than the number of transplants performed each year. This article highlights current immunosuppression protocols and the newer immunosuppressive drugs under investigation in a number of multicenter trials. These hold out the promise of reducing the frequency of acute rejection and of prolonging graft survival. They are divided into three groups. The first, like cyclosporine, interferes with the action of interleukin 2. The second, like azathioprine, are antimetabolites; and the third, new monoclonal antibodies. The use of antibody-induction therapy is compared with standard regimens. There are risks related to prednisone withdrawal protocols and inadequate cyclosporine dosing that may lead to accelerated graft loss. Cardiovascular disease is a significant problem in older diabetic patients for whom coronary angiography is recommended. A defined set of risk factors is outlined that predicts which younger diabetic patients should have a cardiovascular evaluation. Chronic liver disease is a growing problem and rational strategies are emerging from studies of patients with biopsy-proven active hepatitis. The presence of hepatic inflammation is associated with progressive liver disease and patients must be made aware of this risk when seeking transplantation. A large number of studies of various prophylactic regimens are starting to provide data on the cost-effective reduction of cytomegalovirus disease in transplant recipients. It is recommended that patients receiving antibody therapy also receive preemptive gangciclovir. The issue of chronic allograft rejection is discussed briefly. The most important predictors of chronic allograft rejection are the frequency of acute rejection, inadequate immunosuppression, and infections.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
New immunosuppressive drugs show promise for reducing kidney transplant rejection and improving graft survival. Research explores novel therapies and compares them with standard protocols to enhance patient outcomes in transplantation.
Area of Science:
- Transplantation immunology
- Nephrology
- Immunopharmacology
Background:
- Significant disparity exists between kidney transplant demand and organ availability.
- Acute rejection and chronic allograft nephropathy are major challenges in transplantation.
- Cardiovascular disease and chronic liver disease pose risks for transplant candidates.
Purpose of the Study:
- To review current immunosuppression protocols in kidney transplantation.
- To highlight novel immunosuppressive drugs and antibody-induction therapies.
- To discuss risk factors for graft loss, cardiovascular events, and liver disease in transplant recipients.
Main Methods:
- Review of multicenter trials investigating new immunosuppressive drugs.
- Comparison of antibody-induction therapy with standard immunosuppression regimens.
- Analysis of risk factors for graft loss, cardiovascular disease, and hepatic inflammation.
Main Results:
- Newer immunosuppressants targeting interleukin 2 and antimetabolites offer potential for improved outcomes.
- Antibody-induction therapy presents an alternative to standard immunosuppression protocols.
- Risk factors for accelerated graft loss, cardiovascular events in diabetic patients, and progressive liver disease are identified.
Conclusions:
- Novel immunosuppressive agents and strategies hold promise for reducing acute rejection and prolonging kidney graft survival.
- Careful management of immunosuppression, including cyclosporine dosing and prednisone withdrawal, is crucial.
- Prophylaxis against cytomegalovirus (CMV) disease, particularly with ganciclovir during antibody therapy, is recommended.