Urinary cytokines and steroid responsiveness in idiopathic nephrotic syndrome of childhood

Am J Nephrol. 2008;28(1):83-90. doi: 10.1159/000109396. Epub 2007 Oct 3.

Abstract

Background/aim: Steroid-resistant nephrotic syndrome (SRNS) has been associated with activation of TGF-beta(1) and progression to chronic kidney disease. Steroid-sensitive nephrotic syndrome (SSNS) has been associated with activation of T-cells and favorable outcome. Our objective was to distinguish SRNS from SSNS and focal segmental glomerulosclerosis (FSGS) from minimal change disease (MCD) on the basis of urinary cytokine profile.

Method: We used a high-throughput cytokine array. ICAM-1 and TGF-beta(1) in urine and kidney tissue were evaluated by ELISA and immunohistochemistry (IHC), respectively.

Results: Age, gender, race, body mass index, and glomerular filtration rate were similar among groups. There were no statistically significant differences between SRNS (n = 12) and SSNS (n = 12) in regard to the presence of hypertension, treatment with ACE inhibitors, and renal histology. Arrays detected a 1- to 5.5-fold increase in urinary cytokine expression in subjects with idiopathic nephrotic syndrome (INS) as compared to controls. Using ELISA, urinary excretion of ICAM-1 was significantly higher in INS subjects than in controls (control group, n = 12; p = 0.005), but it did not differentiate SRNS from SSNS, or FSGS from MCD. IHC failed to reveal differences in renal tissue expression of ICAM-1 among controls, SRNS and SSNS. There were no significant differences among controls, and patients with SRNS and SSNS in the urinary excretion of TGF-beta(1) (p = 0.21). However, urinary TGF-beta(1) levels were significantly higher in FSGS than in MCD (p = 0.03), and IHC showed increased immunoreactivity in FSGS.

Conclusion: Our data indicate that urinary TGF-beta(1) was able to differentiate between FSGS and MCD but was not a biomarker of steroid responsiveness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biomarkers / urine*
  • Child
  • Collagen Type IV / metabolism
  • Diagnosis, Differential
  • Drug Resistance
  • Female
  • Glomerulosclerosis, Focal Segmental / drug therapy
  • Glomerulosclerosis, Focal Segmental / urine
  • Humans
  • Intercellular Adhesion Molecule-1 / urine
  • Male
  • Nephrosis, Lipoid / drug therapy
  • Nephrosis, Lipoid / urine
  • Nephrotic Syndrome / drug therapy*
  • Nephrotic Syndrome / urine*
  • Protein Array Analysis
  • Steroids / therapeutic use*
  • Transforming Growth Factor beta1 / urine*

Substances

  • Biomarkers
  • Collagen Type IV
  • Steroids
  • Transforming Growth Factor beta1
  • Intercellular Adhesion Molecule-1