Long‐term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Abstract

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.

Posttransplant metabolic syndrome in children and adolescents after liver transplantation: A systematic review

“…Fifty percent of the 16 studies included in this review relied on the use of antihypertensive medications as evidence of hypertension, and 13% provided no definition 22, 23, 27, 33‐45. Estimates of the prevalence of hypertension from these studies vary from 4% to 100% (Table 2).…”

“…Six studies (37%) applied age‐ and sex‐specific BP percentiles in addition to medication regimens. Three of the 4 studies that used percentiles to report the prevalence of hypertension 5 to 10 years after transplantation estimated the prevalence to be 20% to 28%27, 33, 40; 1 study reported a lower prevalence 34. The 2 studies that reported hypertension 1 year after transplantation estimated a prevalence of 58% to 64%, although the majority of these children were receiving CSA 35, 36.…”

Pharmacogenetics in immunosuppressants: impact on dose requirement of calcineurin inhibitors in renal and liver pediatric transplant recipients

“…CsA and TAC serve as a cornerstone of immunosuppressive regimens in pediatric solid organ transplantation [5]. Both drugs have similarity of mode of action, efficacy, and side effects; however, they are chemically unrelated and have certain differences affecting the choice of either of them in immunosuppressive treatment [5,6].…”

“…Both drugs have similarity of mode of action, efficacy, and side effects; however, they are chemically unrelated and have certain differences affecting the choice of either of them in immunosuppressive treatment [5,6].…”

Pediatric Liver Transplantation

“…CNI share a number of side effects in common including nephrotoxicity, neurotoxicity, and hyperlipidemia [57]. There are, however, some differences between tacrolimus and cyclosporin.…”