Urinary Cytokines and Steroid Responsiveness in Idiopathic Nephrotic Syndrome of Childhood

Abstract

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.

NGAL distinguishes steroid sensitivity in idiopathic nephrotic syndrome

“…Major limitations of that study are that (1) the peptides in the signature were not identified, and (2) proteomic signatures have limited clinical value due to the lack of availability of affordable and practical testing procedures. A later attempt was made to determine if a urinary cytokine panel could distinguish steroid responsiveness in pediatric idiopathic NS [25]. While the authors demonstrated that a high-throughput cytokine array, including ICAMI, could distinguish patients with NS from controls, it did not differentiate steroid responsiveness.…”

TGF-beta signal transduction in chronic kidney disease

“…Increased urinary TGF-beta is detected in patients with some forms of nephrotic syndrome (6), IgA nephropathy (7), and focal segmental glomerulosclerosis (FSGS) (7, 8). Interestingly, while detection of TGF-beta in the urine can differentiate between FSGS and the non-fibrotic process of minimal change disease (8), TGF-beta levels cannot be used predict response to corticosteroid therapy, despite the fact that some anti-fibrotic treatments may reduce these levels (9). In human FSGS (10) and in experimental models of renal fibrosis (11), TGF-beta is closely associated with ECM accumulation.…”

Chemokines as Potential Markers in Pediatric Renal Diseases

“…For instance, CCL2/MCP-1 and CXCL8/IL-8 are the chemokines more commonly associated with pediatric renal diseases [7,11,12,15,16,19,20,46,47,55,58,[65][66][67][68][69][73][74][75].…”

“…Araya and coworkers evaluated 23 patients with MCNS and 8 healthy controls and detected that MCNS patients have impaired T regulatory cells with low levels of IL-10 [8]. Woroniecki and coworkers studying 24 children with INS reported that urinary levels of the fibrogenic cytokine TGF-might differentiate between FSGS and MCNS, but it seemed not to be a biomarker of steroid responsiveness [46]. Our research group measured plasma and urinary chemokines in 32 children with INS divided according to steroid responsiveness into 12 healthy controls [7].…”