Urinary cytokines and steroid responsiveness in idiopathic nephrotic syndrome of childhood.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
Our data indicate that urinary TGF-beta(1) was able to differentiate between FSGS and MCD but was not a biomarker of steroid responsiveness.
Woroniecki
Robert P
RP
Pediatric Nephrology, The Children's Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY 10467, USA. rworonie@aecom.yu.edu
Shatat
Ibrahim F
IF
Supe
Katarina
K
Du
Zhongfang
Z
Kaskel
Frederick J
FJ
D000293:Adolescent; D015415:Biomarkers / Q000652:urine*; D002648:Child; D024141:Collagen Type IV / Q000378:metabolism; D003937:Diagnosis, Differential; D004351:Drug Resistance; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000652:urine; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000652:urine; D008297:Male; D009402:Nephrosis, Lipoid / Q000188:drug therapy / Q000652:urine; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000652:urine*; D040081:Protein Array Analysis; D013256:Steroids / Q000627:therapeutic use*; D053773:Transforming Growth Factor beta1 / Q000652:urine*
D015415:Biomarkers; D024141:Collagen Type IV; D013256:Steroids; D053773:Transforming Growth Factor beta1; D018799:Intercellular Adhesion Molecule-1