Beneficial role of ketoconazole in kidney recipients

 The Americans journal of Kidney Disease (2001:37:510-517) has reported the results of a study on the long term administration of the antifungal agent ketoconazole to kidney transplant recipient treat with Cyclosporine A. This study was conducted at the University of Mansoura in Egypt. The study comprised of 51 kidney transplant recipients who received both Cyclosporine A and Ketoconazole and 49 similar control subjects who were given Cyclosporine only. It was found at Cyclosporine a dose requirements were significantly reduced in the test group at all points throughout the study. The test group also had fewer fungal skin infection and low levels of serum Cholesterol, low-density lipoproteins and triglycerides than the control subjects.

The frequency of acute rejection episodes was similar in both groups; however the control subjects had a poorer response to treatment, chronic graft dysfunction, and while less frequent in the ketoconazole group in the first post-transplant year, was equally prevalent in both groups by the end of the study. The prevalence of hepatotoxicity also was similar in both groups. Cyclosporine an induced nephrotoxicity initially was worse in the ketoconazole group, but it rapidly improved after reduction in cyclosporine a dosage. 

Report from India about feasibility of stopping Cyclosporine in renal transplant recipients

Dr. Anant Kumar and his colleagues, from the Sanjay Gandhi Postgraduate institute of Medical Science in Luck know have been working on a study to determine the outcome of withdrawing Cyclosporine A in renal transplant recipients. The study revealed that in renal transplantation from a living related donor, 12 months of Cyclosporine should be very slow, over a period of 3 months. In addition, the doses of azathioprine and prednisolone should be stepped up before reduction in the Cyclosporine dose is started.

The study comprised of 252 patients in a live related transplant program. 99 patients “marking up the early Cyclosporine withdrawal” group, stopped taking the drug 9 months after transplantation over a 4 week period,44 patients making up the “late Cyclosporine withdrawal “group stopped the drug a median of 16 months post op over an 8 week period. The remaining 109 patients continued on low-dose Cyclosporine indefinitely

Early Cyclosporine withdrawal was associated with a significant risk of acute and chronic rejection. Acute rejection episodes occurred in roughly 54% of patients in the early withdrawal group and 31% of the low-dose group as against only 23% of the last withdrawal group. More than 40% of patients who had acute rejection episodes after stopping Cyclosporine early eventually lost their grafts due to uncontrolled acute rejection or chronic rejection

As far as long-term low dose Cyclosporine A therapy was concerned, Dr. Kumar and his colleagues, found that it had the highest need for antihypertensive medication, thereby demonstrating that long-term low dose Cyclosporine A had no beneficial effects in terms of grafts function and provided inferior blood pressure control.

Of interest is the fact that withdrawing Cyclosporine A after 1 year has apparently been proven feasible in cadaveric renal transplantation, as well.