Plasma Cytokine Profiling to Predict Steroid Resistance in Pediatric Nephrotic Syndrome.
Kidney Int Rep
; 6(3): 785-795, 2021 Mar.
Article
em En
| MEDLINE
| ID: mdl-33732993
ABSTRACT
INTRODUCTION:
Glucocorticoids (GCs) are the primary treatment for nephrotic syndrome (NS), although â¼10% 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 â¼7 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+ TH1 cells and TH2 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.
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Base de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article