Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome

Abstract

Introduction Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although ∼10% to 20% of children develop steroid-resistant NS (SRNS). Unfortunately, there are no validated biomarkers able to predict SRNS at initial disease presentation. We hypothesized that a plasma cytokine panel could predict SRNS at disease presentation, and identify potential pathways regulating SRNS pathogenesis. Methods Paired plasma samples were collected from 26 children with steroid-sensitive NS (SSNS) and 14 with SRNS at NS presentation and after ∼7 weeks of GC therapy, when SSNS versus SRNS was clinically determined. Plasma cytokine profiling was performed with a panel of 27 cytokines. Results We identified 13 cytokines significantly different in Pretreatment SSNS versus SRNS samples. Statistical modeling identified a cytokine panel (interleukin [IL]-7, IL-9, monocyte chemoattractant protein–1 [MCP-1]) able to discriminate between SSNS and SRNS at disease presentation (receiver operating characteristic [ROC] value = 0.846; sensitivity = 0.643; specificity = 0.846). Furthermore, GC treatment resulted in significant decreases in plasma interferon-γ (IFN-γ), tumor necrosis factor–α (TNF-α), IL-7, IL-13, and IL-5 in both SSNS and SRNS patients. Conclusions These studies suggest that initial GC treatment of NS reduces the plasma cytokines secreted by both CD4 + T H 1 cells and T H 2 cells, as well as CD8 + T cells. Importantly, a panel of 3 cytokines (IL-7, IL-9, and MCP-1) was able to predict SRNS prior to GC treatment at disease presentation. Although these findings will benefit from validation in a larger cohort, the ability to identify SRNS at disease presentation could greatly benefit patients by enabling both avoidance of unnecessary GC-induced toxicity and earlier transition to more effective alternative treatments.

Urinary monocyte chemotactic protein 1 as a predictive marker of steroid responsiveness in children with idiopathic nephrotic syndrome

“…Our study has female predominance about 54% and that is in agreement with Agrawal et al, [10] study in which his study group has also female predominance that represent 55%. Our study showed no significant difference was found between patients & control group regarding blood pressure.…”

Steroid Responsiveness and Urinary Monocyte Chemotactic Protein-1 in Children with Nephrotic Syndrome.

“…In another study, Khatibi et al, [18] showed a higher level of uMCP-1 in SRNS patients compared to SSNS patients, indicating that uMCP-1 can predict glucocorticoid resistance. In addition, our findings were consistent with those of Agrawal et al, [19] who found that uMCP-1 may distinguish children with SRNS from those with SSNS at the time of initial disease presentation. Moreover, Angela [16] noted that patients with SRNS higher concentrations of MCP-1 in the urine compared to SSNS patients (p < 0.001).…”

Effect of Huaiqihuang Granules Combined with Comprehensive Nursing on Children with Primary Nephrotic Syndrome

“…Many studies have shown that cytokines are closely related to the pathogenesis of nephropathy [22][23][24]. In many nephropathy-related studies [25][26][27], the expression or concentration levels of serum IFN cytokines presented conflicting results. TNF levels were agreed to be significantly elevated.…”