BACKGROUND AND METHODS: Results of a total of 46 pediatric (mean age; 9.0 years), living-related, cyclosporine-treated renal allograft recipients were analyzed retrospectively to study 1), the effects of an acute rejection on the long-term allograft function and 2), the relationship between the cyclosporine blood levels and the frequency of acute rejections. In addition, sequential allograft biopsies (100 days, one, two and three years post-transplant) were performed in all cases to see if clinical symptoms correlated with histological changes. RESULTS: After a mean follow up of 3.3 (range 1-6) years, 15 of 22 (68%) recipients who had no signs of acute rejection, 6 of 12 (50%) who had acute rejections but responded completely to therapy, and none of the remaining 12 cases who failed to recover completely from acute rejections showed good allograft functions and normal histology on biopsy. Thirty-four of 46 cases had no clinical signs of rejection at 100-day allograft biopsy. Yet, histological changes compatible with acute rejection were noted in 11 of 34. Treatments of the rejection were promptly started on these patients and the prognosis was excellent in six cases. The mean blood trough levels of cyclosporine were significantly lower in patients who developed an acute rejection during the first week following transplantation as compared to those without rejection episodes during the same period, 165.5 ng/ml and 204.1 ng/ml, respectively. Furthermore, the mean blood cyclosporine trough levels in patients who experienced rejections during two, three and five weeks after transplantation were definitely lower than those who did not experience such episodes; 124.5 ng/ml, 101 ng/ml and 149.3 ng/ml versus 241.7 ng/ml, 217.7 ng/ml and 201.1 ng/ml respectively, although the number of the cases was too small to reach statistical significance. CONCLUSION: The results indicate that the long-term allograft function would depend on whether there were episodes of acute rejections, and/or how the allograft responded to the treatments. Since the introduction of cyclosporine has made it difficult to detect acute rejections by clinical findings alone such as blood chemistry or urinalysis, the role of routine allograft biopsies is very important in renal transplantation. It seems likely that low blood levels and/or acute decline of cyclosporine during early postransplant period could increase the possibility of episodes of acute rejection. Since it is well documented that cyclosporine induces less renal parenchymal damages in children, the blood through levels of the drug should be kept at between 200 and 300 ng/ml within 5 weeks of transplantation in order to reduce the risk of acute rejections and to improve the chance of long-term allograft survival.
BACKGROUND AND METHODS: Results of a total of 46 pediatric (mean age; 9.0 years), living-related, cyclosporine-treated renal allograft recipients were analyzed retrospectively to study 1), the effects of an acute rejection on the long-term allograft function and 2), the relationship between the cyclosporine blood levels and the frequency of acute rejections. In addition, sequential allograft biopsies (100 days, one, two and three years post-transplant) were performed in all cases to see if clinical symptoms correlated with histological changes. RESULTS: After a mean follow up of 3.3 (range 1-6) years, 15 of 22 (68%) recipients who had no signs of acute rejection, 6 of 12 (50%) who had acute rejections but responded completely to therapy, and none of the remaining 12 cases who failed to recover completely from acute rejections showed good allograft functions and normal histology on biopsy. Thirty-four of 46 cases had no clinical signs of rejection at 100-day allograft biopsy. Yet, histological changes compatible with acute rejection were noted in 11 of 34. Treatments of the rejection were promptly started on these patients and the prognosis was excellent in six cases. The mean blood trough levels of cyclosporine were significantly lower in patients who developed an acute rejection during the first week following transplantation as compared to those without rejection episodes during the same period, 165.5 ng/ml and 204.1 ng/ml, respectively. Furthermore, the mean blood cyclosporine trough levels in patients who experienced rejections during two, three and five weeks after transplantation were definitely lower than those who did not experience such episodes; 124.5 ng/ml, 101 ng/ml and 149.3 ng/ml versus 241.7 ng/ml, 217.7 ng/ml and 201.1 ng/ml respectively, although the number of the cases was too small to reach statistical significance. CONCLUSION: The results indicate that the long-term allograft function would depend on whether there were episodes of acute rejections, and/or how the allograft responded to the treatments. Since the introduction of cyclosporine has made it difficult to detect acute rejections by clinical findings alone such as blood chemistry or urinalysis, the role of routine allograft biopsies is very important in renal transplantation. It seems likely that low blood levels and/or acute decline of cyclosporine during early postransplant period could increase the possibility of episodes of acute rejection. Since it is well documented that cyclosporine induces less renal parenchymal damages in children, the blood through levels of the drug should be kept at between 200 and 300 ng/ml within 5 weeks of transplantation in order to reduce the risk of acute rejections and to improve the chance of long-term allograft survival.
Authors: K Morita; T Seki; H Kakizaki; I Takeuchi; T Yamashita; T Chikaraishi; K Kanagawa; T Hirano; K Nonomura; T Koyanagi Journal: Int Urol Nephrol Date: 1998 Impact factor: 2.370