Genetic and in vivo determinants of glucocorticoid sensitivity in relation to clinical outcome of childhood nephrotic syndrome

Kidney Int. 2014 Jun;85(6):1444-53. doi: 10.1038/ki.2013.531. Epub 2014 Jan 15.


Following initial glucocorticoid treatment, the clinical course in children with nephrotic syndrome is highly variable. Intrinsic sensitivity to glucocorticoids might be a determinant of this variability. Functional polymorphisms of the glucocorticoid receptor gene NR3C1 have been associated with either relatively impaired (GR-9β) or increased (BclI) glucocorticoid sensitivity. Here, in a prospective, well-defined cohort of children with nephrotic syndrome, we evaluated both carriage of GR-9β+TthIII-1 and BclI haplotypes in 113 children and a dexamethasone suppression test in 90 children in relation to their clinical outcome over a median follow-up of 4.4 years. Carriers of GR-9β+TthIII-1 had a significantly higher incidence of steroid dependence 13/25 (52%) compared with noncarriers 19/75 (25%) with a hazard ratio adjusted for gender, age, and descent of 3.04 with 95% confidence interval 1.37-6.74. Both first and frequent relapses happened significantly more often in GR-9β+TthIII-1 carriers than in noncarriers. There were no significant differences in therapeutic outcomes between carriers and noncarriers of the BclI haplotype. Results of the dexamethasone test showed no associations with clinical outcome. Thus, the GR-9β+TthIII-1 haplotype of the glucocorticoid receptor gene offers new insights into the clinical course of children with nephrotic syndrome.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Child
  • Child, Preschool
  • Dexamethasone
  • Female
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use*
  • Haplotypes
  • Humans
  • Male
  • Nephrotic Syndrome / diagnosis
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / genetics*
  • Netherlands
  • Pharmacogenetics
  • Phenotype
  • Polymorphism, Genetic*
  • Predictive Value of Tests
  • Prednisolone / adverse effects
  • Prednisolone / therapeutic use*
  • Prospective Studies
  • Receptors, Glucocorticoid / agonists*
  • Receptors, Glucocorticoid / genetics*
  • Recurrence
  • Remission Induction
  • Risk Factors
  • Time Factors
  • Treatment Outcome


  • Glucocorticoids
  • NR3C1 protein, human
  • Receptors, Glucocorticoid
  • Dexamethasone
  • Prednisolone

Associated data

  • NTR/255