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  • Title: Urinary cytokines and steroid responsiveness in idiopathic nephrotic syndrome of childhood.
    Author: Woroniecki RP, Shatat IF, Supe K, Du Z, Kaskel FJ.
    Journal: Am J Nephrol; 2008; 28(1):83-90. PubMed ID: 17914249.
    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.
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