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

ABSTRACT

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.

KEYWORDS:

• Glomerulonephritis
• Prednisone
• Genetic polymorphism
• Steroid-resistant
• Pharmacogenetics
• Personalized medicine
• Steroids

Article highlights

• Identifying molecular pathways involved in pharmacokinetics of steroids provides benefits in glucocorticoid therapy.

• Progress in pharmacogenetic will provide substantial improvements in patients treatment and prediction of response to steroid therapy.

• Polymorphisms in glucocorticoid receptors, their transportation and metabolizing enzymes affect drug clearance.

• Genetic testing is beneficial to determine personalized GC regimens and creates insights into the treatment responses.

• Despite its usefulness in patient treatment, genetic testing is not a common test throughout the world.

• Further experiments are required to recognize effective polymorphisms in different ethnics and populations.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

M.A., N.S. and S.Z.V set up the study. SM.H, H.MS, M.B., Z.N.S.F. and SM.H.K. were involved in literature review and preparing the draft. S.Z.V and M.A. revised the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This paper was not funded.