Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence

J Am Soc Nephrol. 2014 Jun;25(6):1342-8. doi: 10.1681/ASN.2013080852. Epub 2014 Feb 7.

Abstract

Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Distribution
  • Age of Onset
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Drug Resistance
  • Female
  • Humans
  • Infant
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation*
  • Male
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / epidemiology
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / surgery*
  • Recurrence
  • Renal Dialysis
  • Risk Factors
  • Steroids / therapeutic use*
  • Transcriptome

Substances

  • Biomarkers
  • Steroids