Eva Cuzzoni1, Raffaella Franca2, Sara De Iudicibus3, Annalisa Marcuzzi3, Marianna Lucafò3, Marco Pelin1, Diego Favretto2, Elena Monti4, William Morello5,6, Luciana Ghio5, Claudio La Scola4, Francesca Mencarelli4, Andrea Pasini4, Giovanni Montini5,6, Giuliana Decorti7,8, Gabriele Stocco1. 1. Department of Life Sciences, University of Trieste, Trieste, Italy. 2. Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, 34127, Italy. 3. Institute for Maternal Health - IRCCS "Burlo Garofolo", Trieste, Italy. 4. Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant'Orsola, Bologna, Italy. 5. Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy. 6. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. 7. Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, 34127, Italy. decorti@units.it. 8. Institute for Maternal Health - IRCCS "Burlo Garofolo", Trieste, Italy. decorti@units.it.
Abstract
PURPOSE: Idiopathic nephrotic syndrome (INS) is the most frequent form of childhood nephrotic syndrome. Steroids represent the best therapeutic option; however, inter-individual differences in their efficacy and side effects have been reported. To date, there is no way to predict patients' resistance and/or dependence. Alterations in the cytokine profile of INS patients might contribute to proteinuria and glomerular damage and affect drug sensitivity. METHODS: The cytokine plasma levels were measured in 21 INS children at diagnosis to investigate the association among cytokines pattern and clinical response. Patients were selected on the basis of their clinical response: 7 steroid sensitive (SS), 7 dependent (SD), and 7 resistant (SR). Significant results were then analyzed in 41 additional pediatric INS patients. RESULTS: Within the 48 cytokines analyzed, macrophage migration inhibitory factor (MIF) was a good predictor of steroid response. Indeed, SR patients showed significantly higher MIF plasma levels compared with all others (p = 0.022; OR = 4.3, 95%CI = 1.2-25.4): a cutoff concentration of MIF > 501 pg/ml significantly discriminated SR patients (sensitivity = 85.7%, specificity = 71.4%). On the contrary, SD patients showed lower MIF plasma levels compared with others (p = 0.010; OR = 0.12, 95%CI = 9.2 × 10-3-6.7 × 10-1). Significant results were confirmed in the entire cohort. CONCLUSIONS: Our comprehensive cytokine analysis indicates that assessing MIF plasma levels at diagnosis could predict response to glucocorticoids in children with INS.
PURPOSE:Idiopathic nephrotic syndrome (INS) is the most frequent form of childhood nephrotic syndrome. Steroids represent the best therapeutic option; however, inter-individual differences in their efficacy and side effects have been reported. To date, there is no way to predict patients' resistance and/or dependence. Alterations in the cytokine profile of INS patients might contribute to proteinuria and glomerular damage and affect drug sensitivity. METHODS: The cytokine plasma levels were measured in 21 INS children at diagnosis to investigate the association among cytokines pattern and clinical response. Patients were selected on the basis of their clinical response: 7 steroid sensitive (SS), 7 dependent (SD), and 7 resistant (SR). Significant results were then analyzed in 41 additional pediatric INS patients. RESULTS: Within the 48 cytokines analyzed, macrophage migration inhibitory factor (MIF) was a good predictor of steroid response. Indeed, SR patients showed significantly higher MIF plasma levels compared with all others (p = 0.022; OR = 4.3, 95%CI = 1.2-25.4): a cutoff concentration of MIF > 501 pg/ml significantly discriminated SR patients (sensitivity = 85.7%, specificity = 71.4%). On the contrary, SDpatients showed lower MIF plasma levels compared with others (p = 0.010; OR = 0.12, 95%CI = 9.2 × 10-3-6.7 × 10-1). Significant results were confirmed in the entire cohort. CONCLUSIONS: Our comprehensive cytokine analysis indicates that assessing MIF plasma levels at diagnosis could predict response to glucocorticoids in children with INS.
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