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MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome

  • Pharmacodynamics
  • Published:
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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.

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Acknowledgments

We thank all the members of Nefrokid Study Group, whose collaboration was essential in order to perform the study. The following institutions participated in the study: Ospedale della Gruccia Montevarchi (Arezzo); Ospedale San Donato Arezzo; Ospedale di Asola - Asola (MN); Policlinico-ospedale Giovanni XXIII, Bari; AUO di Bologna, Policlinico S.Orsola-Malpighi; Ospedale dei Bambini di Brescia; AUSL Modena Presidio Ospedaliero Carpi, Ospedale Ramazzini; AUSL di Cesena Ospedale Maurizio Bufalini; Ospedale di Circolo di Desio (MI); Ospedale di Esine (BS); A.O.Universitaria di Ferrara, Arcispedale S. Anna; Azienda Ospedaliera Universitaria Meyer Firenze; Ospedale Gaslini, Genova; Ospedale Santa Maria della Scaletta, AUSL di Imola; Ospedale “C. Poma” - Mantova; Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico - Milano; Ospedale dei Bambini “Vittore Buzzi” - Milano; Azienda Ospedaliero-Universitaria Policlinico di Modena; Fondazione MBBM, S. Gerardo - Monza; ARNAS Civico, Di Cristina e Fatebenefratelli, Palermo; AO San Salvatore Pesaro; Ospedale Guglielmo da Saliceto, Piacenza; Ospedale Santa Maria degli Angeli, Pordenone; AO. Santa Maria Nuova di Reggio Emilia; Ospedale degli Infermi Rimini; Ospedale Generale Provinciale di Saronno (VA); Nuovo Ospedale Civile Sassuolo; Ospedale di Circolo Galmarini - Tradate (VA); Ospedale Pediatrico “Burlo Garofalo,” Trieste; Ospedale “Filippo Del Ponte” - Varese; Ospedale di Vimercate (MI).

Funding

EC was supported by the Italian Society of Pharmacology grant SIF-MSD Italy 2015. We would also thank the charity organization “Il Sogno di Stefano” and The Nando Peretti Foundation for their generous financial support.

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Authors and Affiliations

  1. Department of Life Sciences, University of Trieste, Trieste, Italy

    Eva Cuzzoni, Marco Pelin & Gabriele Stocco

  2. Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, 34127, Italy

    Raffaella Franca, Diego Favretto & Giuliana Decorti

  3. Institute for Maternal Health - IRCCS “Burlo Garofolo”, Trieste, Italy

    Sara De Iudicibus, Annalisa Marcuzzi, Marianna Lucafò & Giuliana Decorti

  4. Nephrology and Dialysis Unit, Department of Pediatrics, Azienda Ospedaliera Universitaria Sant’Orsola, Bologna, Italy

    Elena Monti, Claudio La Scola, Francesca Mencarelli & Andrea Pasini

  5. Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy

    William Morello, Luciana Ghio & Giovanni Montini

  6. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    William Morello & Giovanni Montini

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  1. Eva Cuzzoni
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Contributions

Eva Cuzzoni designed the research, wrote the manuscript, planned and performed experiments, and analyzed data; Raffaella Franca wrote and revised the manuscript; Sara De Iudicibus designed the research and analyzed data; Annalisa Marcuzzi performed experiments and analyzed data; Marianna Lucafò performed experiments and analyzed data; Marco Pelin performed experiments; Diego Favretto performed experiments; William Morello enrolled patients and revised the manuscript, Luciana Ghio enrolled patients and revised the manuscript, Claudio La Scola enrolled patients and revised the manuscript, Francesca Mencarelli enrolled patients and revised the manuscript, Andrea Pasini designed the research, enrolled patients and revised the manuscript; Giovanni Montini designed the research, enrolled patients and revised the manuscript; Giuliana Decorti analyzed data and revised the manuscript; Gabriele Stocco analyzed data, wrote and revised the manuscript.

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Correspondence to Giuliana Decorti.

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Cuzzoni, E., Franca, R., De Iudicibus, S. et al. MIF plasma level as a possible tool to predict steroid responsiveness in children with idiopathic nephrotic syndrome. Eur J Clin Pharmacol 75, 1675–1683 (2019). https://doi.org/10.1007/s00228-019-02749-3

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