期刊
KIDNEY INTERNATIONAL
卷 85, 期 6, 页码 1444-1453出版社
ELSEVIER SCIENCE INC
DOI: 10.1038/ki.2013.531
关键词
child; dexamethasone suppression test; frequent relapses; glucocorticoid receptor; nephrotic syndrome; prednisolone
资金
- Dutch Kidney Foundation [C03.2072]
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-9 beta) or increased (Bc/I) glucocorticoid sensitivity. Here, in a prospective, well-defined cohort of children with nephrotic syndrome, we evaluated both carriage of GR-9 beta + TthIII-1 and Bc/I 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-9 beta + 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-9 beta + TthIII-1 carriers than in noncarriers. There were no significant differences in therapeutic outcomes between carriers and noncarriers of the Bc/I haplotype. Results of the dexamethasone test showed no associations with clinical outcome. Thus, the GR-9 beta + TthIII-1 haplotype of the glucocorticoid receptor gene offers new insights into the clinical course of children with nephrotic syndrome.
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