Molecular basis of mechanisms of steroid resistance in children with nephrotic syndrome

Acta Biochim Pol. 2013;60(3):339-44. Epub 2013 Aug 1.

Abstract

Steroid therapy, due to a wide range of anti-inflammatory properties of steroids, is a basic field of treatment in many human diseases including the nephrotic syndrome in children. However, not all patients respond positively to therapy which divides them into steroid sensitive (SS) and steroid resistance (SR) individuals. Many potential factors associated with steroid resistance have been identified so far. It seems that genetic factors associated with glucocorticoid receptor α (GRα), the structure of heterocomplex of GR as well as glycoprotein P or cytochrome P450 may play a role in the induction of glucocorticoid resistance. Here we described several of the molecular mechanisms, which can regulate glucocorticoid sensitivity and resistance. Moreover, we presented genetic defects, which can lead to various effects of treatment and, in a longer perspective, enable clinicians to individualize therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Anti-Inflammatory Agents / therapeutic use*
  • Child
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Tolerance / genetics*
  • Genetic Predisposition to Disease
  • Glucocorticoids / therapeutic use*
  • Humans
  • Kidney / metabolism
  • Kidney / pathology
  • Metabolism, Inborn Errors / genetics*
  • Metabolism, Inborn Errors / metabolism
  • Metabolism, Inborn Errors / pathology
  • Mutation
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / metabolism
  • Nephrotic Syndrome / pathology
  • Polymorphism, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Receptors, Glucocorticoid / deficiency*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Anti-Inflammatory Agents
  • Glucocorticoids
  • Protein Isoforms
  • Receptors, Glucocorticoid
  • glucocorticoid receptor alpha
  • Cytochrome P-450 Enzyme System

Supplementary concepts

  • Glucocorticoid Receptor Deficiency