

The importance of determining the concentration of myco- phenolic acid in children with steroid-dependent nephrotic syndrome
https://doi.org/10.21508/1027-4065-2024-69-4-63-69
Abstract
Despite the significant effectiveness of steroid therapy, specialists face serious difficulties in managing patients with steroid-dependent nephrotic syndrome, which requires the prescription of immunosuppressive therapy. Among the available adjuvant drugs, mycophenolate mofetil stands out as a preferred option due to its safety profile, good tolerability, and high efficacy. Currently, only a few studies are presented in the literature on the effectiveness of the use of mycophenolic acid in children with nephrotic syndrome, which is explained by the complexity of the pharmacokinetics of the drug.
The article presents the results of a study whose purpose was to evaluate the value of determining mycophenolic acid in patients with steroid-dependent nephrotic syndrome to maintain stable clinical and laboratory remission of the disease.
The study examined 78 patients aged 1 to 18 years with steroid-dependent nephrotic syndrome. The results demonstrated that determination of mycophenolic acid concentrations in children with steroid-dependent nephrotic syndrome is an effective method for monitoring therapy for nephrotic syndrome in aunts. Determining the concentration of mycophenolic acid at the C0 point is a highly specific and sensitive method for predicting the development of relapses of the disease, while a mycophenolic acid concentration level of more than 3.2 μg/ml can serve as a minimum guideline for monitoring the use of mycophenolic acid in children with steroid-dependent nephrotic syndrome.
Keywords
About the Authors
S. L. MorozovRussian Federation
Moscow
V. V. Dlin
Russian Federation
Moscow
V. A. Obukhova
Russian Federation
Moscow
E. K. Petrosyan
Russian Federation
Moscow
I. V. Zolkina
Russian Federation
Moscow
V. P. Pakhomova
Russian Federation
Moscow
V. Yu. Voinova
Russian Federation
Moscow
References
1. Trautmann A., Boyer O., Hodson E., Bagga A., Gipson D.S., Samuel S. et al. IPNA clinical practice recommendations for the diagnosis and management of children with steroid-sensitive nephrotic syndrome. Pediatr Nephrol [Internet] 2023; 38(3): 877–919. DOI: 10.1007/s00467–022–05739–3
2. Ehren R., Benz M.R., Brinkkötter P.T., Dötsch J., Eberl W.R., Gellermann J. et al. Pediatric idiopathic steroid-sensitive nephrotic syndrome: diagnosis and therapy–short version of the updated German best practice guideline (S2e) — AWMF register no. 166–001, 6/2020. Pediatr Nephrol [Internet] 2021; 36(10): 2971–2985. DOI: 10.1007/s00467–021–05135–3
3. Morozov S.L., Kursova T.S., Petrosyan E.K., Piruzieva O.R., Dlin V.V. Mycophenolate mofetil in the treatment of primary nephrotic syndrome in children. Rossiyskiy vestnik perinatologii i pediatrii 2023; 68(2): 22–28. (in Russ.) DOI: 10.21508/1027–4065–2023–68–2–22–28
4. Morozov S.L., Aksenova M.E. Primary nephrotic syndrome in children. Prospects for personalized therapy. Prakticheskaya meditsina 2018; 8: 39–42. (in Russ.)
5. Morozov S.L., Dlin V.V. On the issue of steroid therapy for primary nephrotic syndrome in children. Prakticheskaya meditsina 2020; 18(3): 26–31. (in Russ.)
6. Ostalska-Nowicka D., Malinska A., Silska M., Perek B., Zachwieja J., Nowicki M. Mycophenolate mofetil (MMF) treatment efficacy in children with primary and secondary glomerulonephritis. aoms. 2011; 6: 1042–1048. DOI: 10.5114/aoms.2011.26618
7. Sobiak J., Resztak M., Chrzanowska M., Zachwieja J., Ostalska-Nowicka D. The Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for Mycophenolic Acid in Children with Nephrotic Syndrome. Molecules 2021; 26(12): 3723. DOI: 10.3390/molecules26123723
8. Kiang T.K.L., Ensom M.H.H. Population Pharmacokinetics of Mycophenolic Acid: An Update. Clin Pharmacokinet 2018; 57(5): 547–558. DOI: 10.1007/s40262–017–0593–6
9. Chen B., Gu Z., Chen H., Zhang W., Fen X., Cai W. et al. Establishment of High-Performance Liquid Chromatography and Enzyme Multiplied Immunoassay Technology Methods for Determination of Free Mycophenolic Acid and Its Application in Chinese Liver Transplant Recipients. Therapeutic Drug Monitoring 2010; 32(5): 653–660. URL: https://ouci.dntb.gov.ua/en/works/4gXM3ZEl/
10. Rong Y., Jun H., Kiang T.K.L. Population pharmacokinetics of mycophenolic acid in paediatric patients. Br J Clin Pharma [Internet] 2021; 87(4): 1730–1757. DOI: 10.1111/bcp.14590
11. Sobiak J., Resztak M., Ostalska-Nowicka D., Zachwieja J., Gąsiorowska K., Piechanowska W. et al. Monitoring of mycophenolate mofetil metabolites in children with nephrotic syndrome and the proposed novel target values of pharmacokinetic parameters. Eur J Pharmaceut Scie 2015; 77: 189–196. DOI: 10.1016/j.ejps.2015.06.017
12. Resztak M., Sobiak J., Czyrski A. Recent Advances in Therapeutic Drug Monitoring of Voriconazole, Mycophenolic Acid, and Vancomycin: A Literature Review of Pediatric Studies. Pharmaceutics [Internet] 2021; 13(12): 1991. DOI: 10.3390/pharmaceutics13121991
13. Ferreira P.C.L., Thiesen F.V., Pereira A.G., Zimmer A.R., Fröehlich P.E. A short overview on mycophenolic acid pharmacology and pharmacokinetics. Clinical Transplantation [Internet] 2020; 34(8): e13997. DOI: 10.1111/ctr.13997
14. Staatz C.E., Tett S.E. Clinical Pharmacokinetics and Pharmacodynamics of Mycophenolate in Solid Organ Transplant Recipients: Clinical Pharmacokinetics [Internet] 2007; 46(1): 13–58. DOI: 10.2165/00003088–200746010–00002
15. Filler G., Todorova E.K., Bax K., Alvarez-Elías A.C., Huang S-H.S., Kobrzynski M.C. Minimum mycophenolic acid levels are associated with donor-specific antibody formation. Pediatr Transplant 2016; 20(1): 34–38. DOI: 10.1111/petr.12637
16. Hackl Á., Cseprekál O., Gessner M., Liebau M.C., Habbig S., Ehren R. et al. Mycophenolate Mofetil Therapy in Children With Idiopathic Nephrotic Syndrome: Does Therapeutic Drug Monitoring Make a Difference? Therapeutic Drug Monitoring [Internet] 2016; 38(2): 274–279. URL: https://www.researchgate.net/publication/283077655_Mycophenolate_Mofetil_Therapy_in_Children_With_Idiopathic_Nephrotic_Syndrome_Does_Therapeutic_Drug_Monitoring_Make_a_Difference
17. Gellermann J., Ehrich J.H.H., Querfeld U. Sequential maintenance therapy with cyclosporin A and mycophenolate mofetil for sustained remission of childhood steroid-resistant nephrotic syndrome. Nephrology Dialysis Transplantation [Internet] 2012; 27(5): 1970–1978. DOI: 10.1093/ndt/gfr572
18. Tellier S., Dallocchio A., Guigonis V., Saint-Marcoux F., Llanas B., Ichay L. et al. Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome. Clin J Am Soc Nephrol [Internet] 2016; 11(10): 1777–1782. URL: https://www.researchgate.net/publication/305518009_Mycophenolic_Acid_Pharmacokinetics_and_Relapse_in_Children_with_Steroid-Dependent_Idiopathic_Nephrotic_Syndrome
19. Djabarouti S., Breilh D., Duffau P., Lazaro E,. Greib C., Caubet O. et al. Steady-state mycophenolate mofetil pharmacokinetic parameters enable prediction of systemic lupus erythematosus clinical flares: an observational cohort study. Arthritis Res Ther [Internet] 2010; 12(6): R217. DOI: 10.1186/ar3202
20. Weber L.T., Shipkova M., Armstrong V.W., Wagner N., Schütz E., Mehls O. et al. Comparison of the Emit immunoassay with HPLC for therapeutic drug monitoring of mycophenolic acid in pediatric renal-transplant recipients on mycophenolate mofetil therapy. Clin Chem 2002; 48(3): 517–525.
Review
For citations:
Morozov S.L., Dlin V.V., Obukhova V.A., Petrosyan E.K., Zolkina I.V., Pakhomova V.P., Voinova V.Yu. The importance of determining the concentration of myco- phenolic acid in children with steroid-dependent nephrotic syndrome. Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics). 2024;69(4):63-69. (In Russ.) https://doi.org/10.21508/1027-4065-2024-69-4-63-69