S.L. MOROZOV^{1, 2}, V.S. PAKHOMOVA¹, V.V. DLIN

¹Scientific-Research Clinical Institute for Pediatrics and Pediatric Surgery named after Academician Yu.E. Veltishchev, Moscow

²Russian National Research Medical University named after N.I. Pirogov, Moscow

 Contact details:

Morozov S.L. — PhD (Medicine), Leading Researcher of the Department of Hereditary and Acquired Kidney Diseases named after Prof. M.S. Ignatova, Associate Professor of the Department of Hospital Pediatrics № 2

Address: 2 Taldomskaya St., Moscow, Russian Federation, 125412, tel.: +7-903-138-77-32, e—mail: mser@list.ru

 Idiopathic nephrotic syndrome is considered the most common glomerulopathy in childhood. Approximately 70–80% of patients will have relapses of nephrotic syndrome after steroid therapy, and half of them will have frequent relapses of the disease, or will develop dependence on steroid therapy, which subsequently requires a decision on steroid-sparing therapy. Currently, there are no methods to predict a patient’s response to a drug before its prescription, and the choice of steroid-sparing immunosuppressive therapy is most often determined by the preferences of the physician, rather than the individual characteristics of the patient. In this regard, it becomes relevant to develop new strategies and approaches aimed at increasing the therapy effectiveness, reducing the frequency of relapses, and minimizing side effects of drugs. In recent years, a new term has appeared in the scientific literature — «pharmacotranscriptomics», aimed at finding RNA biomarkers to predict individual reactions based on the transcriptome profile. This modern field offers new approaches to understanding individual responses to drug therapy based on gene expression analysis and identification of factors influencing these responses. In this paper, we report data from a study aimed at determining the significance of gene expression of interest in cyclosporine metabolism, viewed as pharmacotranscriptomic markers of therapy efficacy in children with steroid-dependent and steroid-resistant nephrotic syndrome. Analysis of genes associated with cyclosporine response revealed that of the genes studied, CYP3A4 and PPIA demonstrated significant differences between patients who achieved remission and those who relapsed during therapy. This result is particularly important since we for the first time characterized the expression profile of these genes in patients receiving calcineurin inhibitors.

Key words: children, nephrotic syndrome, calcineurin inhibitors, cyclosporine, RNA, expression, CYP3A4, PPIA.

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