TY - JOUR
T1 - Urinary cytokines and steroid responsiveness in idiopathic nephrotic syndrome of childhood
AU - Woroniecki, Robert P.
AU - Shatat, Ibrahim F.
AU - Supe, Katarina
AU - Du, Zhongfang
AU - Kaskel, Frederick J.
PY - 2007/11
Y1 - 2007/11
N2 - Background/Aim: Steroid-resistant nephrotic syndrome (SRNS) has been associated with activation of TGF-β1 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-β1 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-β1 (p = 0.21). However, urinary TGF-β1 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-β1 was able to differentiate between FSGS and MCD but was not a biomarker of steroid responsiveness.
AB - Background/Aim: Steroid-resistant nephrotic syndrome (SRNS) has been associated with activation of TGF-β1 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-β1 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-β1 (p = 0.21). However, urinary TGF-β1 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-β1 was able to differentiate between FSGS and MCD but was not a biomarker of steroid responsiveness.
KW - Focal segmental glomerulosclerosis
KW - Intercellular adhesion molecule 1
KW - Protein array
KW - Steroid resistance
KW - Transforming growth factor β
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U2 - 10.1159/000109396
DO - 10.1159/000109396
M3 - Article
C2 - 17914249
AN - SCOPUS:36249032609
SN - 0250-8095
VL - 28
SP - 83
EP - 90
JO - American Journal of Nephrology
JF - American Journal of Nephrology
IS - 1
ER -