Stable graft function after reduction of calcineurin inhibitor dosage in paediatric kidney transplant patients.
BACKGROUND
Chronic calcineurin inhibitor (CNI) toxicity contributes to the development and progression of chronic allograft nephropathy (CAN), which is still the major cause of transplant dysfunction and graft loss. Reduction in dosage of CNI may delay the development of CAN, leading to longer graft survival.


METHODS
Therefore, 19 paediatric kidney transplant patients under immunosuppressive therapy with CNI (12/19 ciclosporin A, CSA, 7/19 tacrolimus, Tac), mycophenolat mofetil and some patients on steroids were included in a prospective study. Over a period of 9 months CNI dosage was stepwise reduced from CSA trough levels of 100-150 ng/ml to 50-70 ng/ml and Tac trough levels of 5-8 ng/ml to 2-3 ng/ml, respectively.


RESULTS
Glomerular filtration rate was stabilized in patients after CSA and Tac reduction. One borderline rejection occurred in a patient prior to reduction of Tac. In patients on CSA, one interstitial cellular rejection (BANFF IA) was noted. Reduction of CNI had no significant effects on blood pressure, lipid status and the infection frequency.


CONCLUSIONS
In paediatric kidney transplant patients, reduction of CNI down to low trough levels stabilizes renal function. However, the risk of acute rejection episodes may be increased. Therefore, further studies based on protocol biopsies within a randomized trial are warranted.
Plank
Christian
C
Klinik für Kinder und Jugendliche, Friedrich-Alexander-Universität Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen, Germany.
Benz
Kerstin
K
Amann
Kerstin
K
Nüsken
Kai-Dietrich
KD
Dittrich
Katalin
K
Rascher
Wolfgang
W
Sauerstein
Katja
K
Stuppy
Anja
A
Klare
Bernd
B
Dötsch
Jörg
J
D000293:Adolescent; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D065095:Calcineurin Inhibitors; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000493:pharmacokinetics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D007223:Infant; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology / Q000601:surgery; D016030:Kidney Transplantation; D008055:Lipids / Q000097:blood; D008297:Male; D008775:Methylprednisolone / Q000493:pharmacokinetics / Q000494:pharmacology; D011446:Prospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D008055:Lipids; D016572:Cyclosporine; D016559:Tacrolimus; D008775:Methylprednisolone