Therapeutic trough mycophenolic acid levels positively correlate with omega-3 fatty acids in leukocytes of children with idiopathic nephrotic syndrome - A pilot study

Sep 28, 2026

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Therapeutic trough mycophenolic acid (MPA) levels were evaluated for their relationship with endoleukocyte fatty acid omega-3 and omega-6 profiles in children with idiopathic nephrotic syndrome (INS). Eighteen pediatric participants, including steroid-sensitive and steroid-resistant subgroups, had fatty acid composition assessed by gas chromatography and trough MPA measured by immunometric assay. In steroid-sensitive patients, higher trough MPA correlated with increased endoleukocyte omega-3 and DHA and decreased omega-6. In steroid-resistant subjects, no such correlations or favorable n-6/n-3 shift were detected, even with adequate MPA levels.

LanguageEnglish

CategoryHealthcare

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Pages9

Reading Time23 min

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Introduction

Idiopathic nephrotic syndrome and treatment context

Immunological mechanisms and drug targets

Mycophenolate mofetil and mycophenolic acid mechanism

Fatty acids and immune modulation

TYPE Original Research PUBLISHED 18 December 2025 DOI 10.3389/fphar.2025.1672304 OPEN ACCESS EDITED BY Johan Vande Walle, Ghent University, Belgium REVIEWED BY Jumpei Saito, National Center for Child Health and Development (NCCHD), Japan Sudarsan K, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), India *CORRESPONDENCE Stefano Turolo, [stefano.turolo@policlinico.mi.it](stefano.turolo@policlinico.mi.it) RECEIVED 24 July 2025 REVISED 26 November 2025 ACCEPTED 11 December 2025 PUBLISHED 18 December 2025 CITATION Turolo S, Edefonti A, Syren M-L, Bellotti AS, Morello W, Collino F, Agostoni C and Montini G (2025) Therapeutic trough mycophenolic acid levels positively correlate with omega-3 fatty acids in leukocytes of children with idiopathicnephrotic syndrome. a pilot study. Front. Pharmacol. 16:1672304 . doi: 10.3389/fphar.2025.1672304 COPYRIGHT © 2025 Turolo, Edefonti, Syren, Bellotti, Morello, Collino, Agostoni and Montini. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Therapeutic trough mycophenolic acid levels positively correlate with omega-3 fatty acids in leukocytes of children with idiopathic nephrotic syndrome. a pilot study Stefano Turolo 1*, Alberto Edefonti 1, Marie-Louise Syren 2, Anita S. Bellotti 1, William Morello 1, Federica Collino 2,3, Carlo Agostoni 2,4 and Giovanni Montini 1,2,3 1Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico. Pediatric Nephrology, Dialysis and Transplant Unit, Milan, Italy, 2Dipartimento di Scienze Cliniche e di Comunità, Dipartimento di Eccellenza 2023-2027, University of Milano, Milan, Italy, 3Laboratory of Translational Research in Paediatric NephroUrology, and Paediatric Nephrology, Dialysis and Transplant Unit, Fondazione Ca’ Granda IRCCSOspedale Maggiore Policlinico, Milan, Italy, 4Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Pediatric Immuno-rheumatology Unit, Milan, Italy The pathogenesis of idiopathic nephrotic syndrome (INS) in most pediatric cases involves immune cell dysfunction, mediated, among other factors, by biologically active polyunsaturated fatty acids-dependent compounds in the blood and cell membranes. The immunosuppressive drug mycophenolate mofetil (MMF) is commonly used to maintain remission in patients with steroid-dependent nephrotic syndrome. The aim of this pilot study was to investigate the effect of trough blood mycophenolic acid (MPA) levels on the endoleukocyte fatty acid omega-3 and omega-6 series. Eighteen pediatric subjects with INS were enrolled, including 12 steroid-sensitive and 6 steroid-resistant children. Fatty acid (FA) profile was analyzed by gas-chromatography, and MPA blood level was evaluated by immunometric assay. Among steroid-sensitive patients, a positive correlation was observed between endoleukocyte omega-3 FA (n-3) and trough blood MPA levels, and a negative correlation was found between endoleukocyte omega-6 FA (n-6) and trough blood MPA levels. In addition, a positive correlation was found between endoleukocyte anti-inflammatory DHA and trough blood MPA levels. In contrast, in steroid-resistant subjects no correlation between endoleukocyte n-6/n-3 ratio and trough blood MPA levels was observed. In conclusion, adequate trough MPA drug levels may have contributed to switch the FA pathway to a more favorable endoleukocyte n-6/n-3 ratio and DHA levels, possibly supporting the natural anti-inflammatory activities of n-3 FA. In steroidresistant NS, despite adequate MPA levels, no promotion of the anti-inflammatory activity of the n-3 series was

FAQs

What was the aim of this pilot study?

To investigate how trough blood mycophenolic acid levels relate to endoleukocyte omega-3 and omega-6 fatty acid series in children with idiopathic nephrotic syndrome.

How were fatty acids and MPA levels measured?

Fatty acid profiles were analyzed by gas chromatography, and trough MPA blood levels were evaluated using an immunometric assay.

What correlations were observed in steroid-sensitive versus steroid-resistant children?

Steroid-sensitive patients showed a positive correlation between endoleukocyte omega-3 (and DHA) and trough MPA, and a negative correlation between endoleukocyte omega-6 and trough MPA. Steroid-resistant patients showed no correlation with the endoleukocyte n-6/n-3 ratio or trough MPA.

Sep 28, 2026

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