ISSN: 2251-8363    eISSN: 2251-8819  
J Nephropathol. 2018;7(3):188-196.
doi:10.15171/jnp.2018.39

Original Article

Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis

Maria Gracia Caletti 1, Juan Ibañez 1, Paulo Caceres Guido 2, Lilien Chertkoff 3, Mara Bonetto 3, Veronica Araoz 3, Paula Schaiquevich 2,4 *

1 Service of Nephrology, Hospital de Pediatría Prof. Dr. JP Garrahan, Buenos Aires, Argentina
2 Clinical Pharmacokinetics Unit, Hospital de Pediatría Prof. Dr. JP Garrahan, Buenos Aires, Argentina
3 Laboratory of Molecular Biology, Genetics Department, Hospital de Pediatría Prof. Dr. JP Garrahan, Buenos Aires, Argentina
4 National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina
*Corresponding author: Paula Schaiquevich, Email; Email: paulas@conicet.gov.ar

Abstract

Background: Pediatric patients with steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) may relapse and current second line agents include mycophenolate mofetil. However, there is no current information about the use of the sodium salt of mycophenolic acid (SMPA) in this population.

Objectives: We conducted a prospective study on the efficacy and pharmacokinetics of SMPA in children with FSGS.

Patients and Methods: Patients without NPHS2 pathogenic variants received SMPA at dosages between 460 to 720 mg/m2/d for 12 months after previous treatments failure. Clinical and biochemical assessments were performed. Blood samples were obtained after the first dose and at steady state (3 months after the onset of treatment) and total and free mycophenolic acid (MPA) was quantitated using HPLC-UV.

Results: Two patients showed partial remission after the 12-month period of SMPA treatment with a notable decrease in proteinuria and an increase in serum albumin levels. Maximum MPA concentrations after the first dose and at steady state were 11.6 µg/mL and 10.5 µg/mL, respectively, without drug accumulation. Maximum MPA free levels after the first dose and at steady state were 192.9 and 120.6 ng/mL, respectively. MPA levels became undetectable after 4 hours of the administration in all cases.

Conclusions: SMPA is a promising agent for pediatric patients with SRNS and FSGS but SMPA schedule of treatment should be revised with shorter intervals of administration and higher doses than those used in the present study in order to attain higher systemic exposures and accumulation of the immunosuppressant drug. Further efficacy and pharmacokinetic studies should be performed to confirm these findings.

Implication for health policy/practice/research/medical education:

Pediatric patients with steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) may develop end-stage renal disease. Pharmacological treatment of these patients is still a challenge to preserve kidney function. Despite mycophenolate mofetil has been proposed as a new treatment, side-effects may lead to treatment withdrawal and data on clinical response is scarce. We here provide evidence of the safety, efficacy and pharmacokinetics of the enteric coated formulation of mycophenolate sodium in pediatric nephrotic syndrome and FSGS.

Please cite this paper as: Caletti MG, Ibañez J, Caceres Guido P, Chertkoff L, Bonetto M, Araoz V, Schaiquevich P. Administration of enteric-coated mycophenolate sodium in children with steroid-resistant nephrotic syndrome and focal segmental glomerulosclerosis. J Nephropathol. 2018;7(3):188-196. DOI: 10.15171/jnp.2018.39.

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