A STUDY TO EVALUATE TROUGH CONCENTRATION OF TACROLIMUS IN CHILDREN WITH STEROID RESISTANT NEPHROTIC SYNDROME

Abstract

Nephrotic Syndrome (NS) is a common kidney disorder in adults and children. It is responsible for significant morbidity and mortality among children globally. The prevalence of childhood NS varies in different population from 12–16/100,000 children affecting all ages and ethnic background. In western countries, the incidence of Nephrotic Syndrome is a 2-3/100,000 child which is slightly higher in population with south Asian origin i.e. 2- 7/100,000. In United States, 2-7 cases per 100,000 children younger than 16 years are reported annually. However, in India the exact incidence and prevalence of this disease are still unknown. The corticosteroids are used as first line treatment of NS. The most of the children with NS initially respond to steroids and achieve remission of proteinuria following 4- 6 weeks of treatment with steroids. However, 10-15% patients do not achieve complete remission and are categorised as steroid resistant Nephrotic Syndrome (SRNS) patients. Recent studies have indicated significant increase in the number of steroid resistant Nephrotic Syndrome particularly in Southeast Asia. SRNS is predominantly treated with calcineurin inhibitors (CNI) drugs like Cyclosporine and Tacrolimus. The Tacrolimus is an immunosuppressive drug that is being prescribed mainly to avoid rejection of organ transplantation. A rigorous literature review revealed that despite its significant clinical use, the pharmacokinetics data and its correlation with therapeutic efficacy is very limited in relation to the Indian paediatric population. It is pertinent to mention that in India, no major studies have been published to find out the trough concentration of Tacrolimus in children with SRNS. The therapeutic dose of Tacrolimus for the treatment of SRNS is extrapolated from kidney transplant patients which appear to be relatively high in the treatment of SRNS. Further, the Tacrolimus has a very narrow therapeutic range which means that a minor decrease in drug dose may affect the treatment and on the other side a minor increase in drug dose may cause nephrotoxicity. The clinical management of SRNS remains a challenging task for nephrologist due to various side effects related to immunosuppression such as infections, nephrotoxicity, cytopenia neurotoxicity and malignancies. Further, the hypoalbuminemia in SRNS may lead to reduced protein binding, and gut edema can lead to uneven absorption of the drug vi which may also be a cause of an altered volume of drug distribution or clearance. Hence, regular therapeutics monitoring of drug is utmost important for the safety and efficacy during the treatment. As the AUC of drug requires multiple samplings, so due to these ethical and procedural limitations the Trough concentrations monitoring of drug has become the popular method in children for monitoring the toxicity and efficacy in clinical practice today.