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A novel approach to the treatment of chronic allograft nephropathy
M R Weir1, L Anderson, J C Fink
1Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA.
Background:
Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft failure. Both nonimmunologic and immunologic mechanisms contribute to this deterioration.
Methods:
Twenty-eight cyclosporine (CsA)-treated renal transplant recipients (21 cadaveric, 5 living, 2 simultaneous kidney-pancreas) with progressive deterioration of renal function were prospectively enrolled in a clinical trial and had their immunosuppressive regimen changed 24.3+/-7.7 months after transplant. All patients had their CsA dose reduced by 50%, azathioprine was discontinued, and mycophenolate mofetil was added to the medical regimen. The mean creatinine of the patients at the initiation of the change in immunosuppression was 3.5+/-1.2 mg/dl (range 1.9 to 6.2 mg/dl).
Results:
Before the change in immunosuppression, the mean loss in renal function as indicated by the least-squares slope of the reciprocal of creatinine versus time was -0.006+/-0.002 (mg/dl)-1 per month. The change in immunosuppression significantly decreased the rate of loss in renal function for most patients when compared with their pretreatment values with a mean slope of 0.007+/-0.003 (mg/dl)-1 per month (P=0.003). Renal function improved in 21 of 28 patients. Only one patient had continued deterioration of renal function. In a multivariate analysis adjusting for CsA dose, mean arterial blood pressure, and baseline creatinine, the change in immunosuppression was significantly associated with improved renal function (P=0.02). There were no acute rejections after the immunosuppression change.
Conclusions:
We conclude that adding mycophenolate mofetil and reducing CsA in patients with chronic deterioration of graft function is well tolerated and results in a short-term improvement in renal function.
Insights
Changing immunosuppression by reducing cyclosporine (CsA) and adding mycophenolate mofetil improved kidney transplant graft function in patients with declining renal function, showing positive short-term outcomes.
Area of Science:
- Nephrology
- Immunosuppression Therapy
- Transplantation Medicine
Background:
- Progressive renal function decline is a primary cause of kidney transplant graft failure.
- Both nonimmunologic and immunologic factors contribute to graft dysfunction.
Purpose of the Study:
- To evaluate the efficacy of modifying immunosuppression in kidney transplant recipients experiencing progressive renal function deterioration.
- To assess the safety and impact of switching from azathioprine to mycophenolate mofetil combined with reduced cyclosporine dosage.
Main Methods:
- A prospective clinical trial involved 28 kidney transplant recipients with declining renal function.
- The immunosuppressive regimen was altered: cyclosporine (CsA) dose reduced by 50%, azathioprine discontinued, and mycophenolate mofetil added.
- Changes were initiated approximately 24 months post-transplant in patients with mean creatinine levels of 3.5 mg/dl.
Main Results:
- The modification significantly decreased the rate of renal function loss (P=0.003).
- Renal function improved in 21 out of 28 patients, with only one experiencing further decline.
- Multivariate analysis confirmed the association between the immunosuppression change and improved renal function (P=0.02), with no acute rejections observed.
Conclusions:
- Adding mycophenolate mofetil and reducing CsA is well-tolerated in kidney transplant recipients with chronic graft function decline.
- This immunosuppression adjustment leads to short-term improvement in renal function.
- The strategy offers a viable option for managing deteriorating graft function post-transplant.