Tacrolimus treatment in childhood refractory nephrotic syndrome: A retrospective study on efficacy, therapeutic drug monitoring, and contributing factors to variable blood tacrolimus levels.

Abstract

Tacrolimus, an immunosuppressive drug, was recommended by the 2012 KDIGO guidelines to treat nephrotic syndrome (NS) in children and adults. However, it has high interpatient pharmacokinetic variability and exposure levels should be monitored, although there are no specified target concentrations. This retrospective study aimed to review efficacy and safety after concomitant treatment with tacrolimus and prednisone, and to identify factors that contribute to the variable blood-trough-concentration-to-dose (C0/Dose) ratio in children with refractory NS (RNS). A 6-month therapy induced complete or partial remission in 95% of patients. One-year follow-up indicated a high remission rate and low nephrotoxicity. Under maintenance dosages, approximately 95% of the C0 values were 2-7 ng/mL. Body weight (BW), age, CYP3A5 polymorphisms were the factors affecting the C0/Dose ratio. The C0/Dose ratio in patients with a BW of <20 kg was 1.5-fold than that in patients with BW of ≥40 kg. Moreover, the C0/Dose ratio in patients aged 1-≤6 and 6-≤12 years was significantly lower than that in patients aged 12-≤18 years, by 25% and 48%, respectively. There were no significant association between CYP3A5 genotyping and C0/Dose ratio in younger children (1-≤6 years), rather than older children (6-≤18 years). In conclusion, routine CYP3A5 genotyping should be considered in children aged over 6 years and exposure levels (C0) of 2-7 ng/mL may be feasible when tacrolimus is combined with low-dose prednisone to treat childhood RNS.

• Authors: Hong-Li Guo, Jing Xu, Jie-Yu Sun, Ling Li, Hui-Lei Guo, Xia Jing, Ze-Yue Xu, Ya-Hui Hu, Ze-Jun Xu, Fang Sun, Xuan-Sheng Ding, Feng Chen, Fei Zhao
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 81 Pg. 106290 (Apr 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32058933 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Immunosuppressive Agents
• Cytochrome P-450 CYP3A
• Prednisone
• Tacrolimus

Topics

• Adolescent
• Child
• Child, Preschool
• Cytochrome P-450 CYP3A (genetics)
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Genotype
• Humans
• Immunosuppressive Agents (therapeutic use)
• Infant
• Male
• Monitoring, Physiologic
• Nephrotic Syndrome (drug therapy)
• Polymorphism, Genetic
• Prednisone (therapeutic use)
• Retrospective Studies
• Tacrolimus (blood, therapeutic use)