Steroid-resistant nephrotic syndrome: pharmacogenetics and epigenetic points and views

Introduction: Glucocorticoids (GCs) are the first-line therapy for patients with nephrotic syndrome (NS), a common glomerular disease, that cause complete remission in most of the cases. In response to the treatment, NS patients are divided into glucocorticoid-sensitive and -resistant. This variation is due to the differences in pharmacokinetics and pharmacodynamics of GCs in each patient that affect the response to the treatment modality. Since the genetic variations in drug-metabolizing enzymes and transporter proteins significantly impact the pharmacokinetics, efficacy and safety of the applied medications, this review highlights the basic mechanisms of genetic variations involved in GCs metabolism in drug-resistant NS patients.Areas covered: This review explains the pharmacogenetic variations that influence the profile of GCs responses and their pharmacokinetics in NS patients. Moreover, the epigenetic variations including histone modifications and miRNA gene regulation that have an influence on GCs responses will review. A comprehensive literature search was performed using different keywords to the reviewed topics.Expert opinion: The accumulative data suggest the importance of pharmacogenetic studies to develop personalized therapies and increase the GCs responsiveness in these patients. It is imperative to know that genetic testing does not give absolute answers to all existing questions in steroid resistance.