Off-label use of tacrolimus in children with glomerular disease: Effectiveness, safety and pharmacokinetics

Glomerular diseases are leading causes of end-stage renal disease in children. Tacrolimus is frequently used off-label in the treatment of glomerular diseases. The effectiveness, safety and pharmacokinetic data of tacrolimus in the treatment of glomerular diseases in children are reviewed in this paper to provide evidence to support its rational use in clinical practice. The remission rates in previously published studies were different. In 19 clinical trials on children with nephrotic syndrome, the overall remission rate was 52.6-97.6%. In four clinical trials on children with lupus nephritis, the overall remission rate was 81.8-89.5%. In a pilot study with paediatric Henoch-Schonlein purpura nephritis patients, the overall remission rate was 100.0%. Infection, nephrotoxicity, gastrointestinal symptoms and hypertension are the most common adverse events. Body weight, age, CYP3A5 genotype, cystatin-C and daily dose of tacrolimus may have significant effects on the pharmacokinetics of tacrolimus in children with glomerular disease. More prospective controlled trials with long follow-up are needed to demonstrate definitely the effectiveness, safety and pharmacokinetics of tacrolimus in children with glomerular diseases.