Ammonium glycyrrhizinate in the complex treatment of steroid-dependent nephrotic syndrome in children
Authors:   Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow Moscow, Russian Federation, Morozov S.L. ,   Pirogov Russian National Research Medical University, Moscow, Russian Federation, Piruzieva O.R. ,   Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow Moscow, Russian Federation, Lepaeva T.V. ,   Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow Moscow, Russian Federation, Nikishina T.A. ,   Veltischev Research and Clinical Institute for Pediatrics and Pediatric Surgery, Pirogov Russian National Research Medical University, Moscow Moscow, Russian Federation
Published: March 2023

The development of resistance to steroid therapy and the formation of dependence (“withdrawal syndrome”) due to secondary adrenal insufficiency on the background of long-term treatment with prednisolone is a topical issue in the management of patients with nephrotic syndrome (NS). Patients and methods. This observational study included 40 children aged 5 to 10 years diagnosed with steroid-dependent nephrotic syndrome (SDNS). The patients were divided into two groups: the study group (n = 20) and the control group (n = 20). All patients received prednisolone in alternating regimens followed by its withdrawal and mofetilic acid medication; patients in the study group additionally received ammonium glycyrrhizinate (AG) over a 24-week course. The follow-up period was 24 weeks with 5 on-site visits (day 0; weeks 2, 4, 12, and 24), during which the cases of disease exacerbations, their duration, the level of proteinuria, and the development of side effects were recorded. The expression levels of ABCB1, NR3C1, CYP3A4, NR1I2 genes were assessed at the 1st and 5th visits in the study group. Results. In the first 1.5 months after prednisolone withdrawal, no child in the study group experienced a recurrence of NS against the background of ammonium glycyrrhizinate therapy, while the control group had a 25% frequency of NS recurrence (n = 5 ) ( p = 0.043). In the study group, the median length of NS remission after prednisolone withdrawal was more than 2.5 months (85.2 ± 39.9 days), while in the control group, NS recurrence occurred more than 2.5 times faster, and remission was only 33 ± 12.3 days (p = 0.009). No statistically significant differences in gene expression (ABCB1, NR3C1, CYP3A4, NR1I2) were found before and after AG treatment in patients in the study group. Conclusion. The inclusion of ammonium glycyrrhizinate during the period of prednisolone therapy withdrawal in patients with SDNS helps to reduce the recurrence rate (glucocorticosteroid withdrawal syndrome) of the disease and significantly prolongs the length of remission. The long-term use of the medication does not lead to an increase in the expression of genes associated with the development of hormone resistance. Key words: children, steroid-dependent nephrotic syndrome, prevention, prednisolone, ammonium glycyrrhizinate