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[Mycophenolate mofetil in treatment of childhood nephrotic syndrome--preliminary report]
Joanna Kwinta-Rybicka1, Katarzyna Wilkosz, Ewa K Wierzchowska-Słowiacze
1Klinika Nefrologii Dzieciecej Uniwersyteckiego, Szpitala Dzieciecego w Krakowie. sekr.nef@wp.pl
Insights
Mycophenolate mofetil (MMF) effectively reduces steroid and cyclosporine use in children with nephrotic syndrome (NS), particularly steroid-dependent cases. This immunosuppressant shows promise for managing difficult NS cases with a favorable safety profile.
Area of Science:
- Pediatric Nephrology
- Immunosuppressive Therapy
- Pharmacology
Background:
- Nephrotic syndrome (NS) management in children presents challenges, especially for steroid-resistant (SR) and steroid-dependent (SD) forms.
- Prolonged steroid, cyclosporine (CsA), and alkylating agent use risks severe complications.
- Mycophenolate mofetil (MMF), an inosine monophosphate dehydrogenase inhibitor, is increasingly explored for NS treatment.
Purpose of the Study:
- To assess the efficacy and safety of MMF in children with SR and SD NS.
- To evaluate MMF's role in reducing reliance on steroids and CsA.
- To investigate MMF's impact on renal function and adverse events in pediatric NS patients.
Main Methods:
- A study involving 19 children (7-19.5 years) with NS, categorized into SD, SD with SR episodes, and SR groups.
- MMF administered orally (180-600 mg/m2/dose, twice daily) for 4-16 months.
- Clinical outcomes (proteinuria, improvement, medication tapering) and renal function (serum cystatin C) were monitored.
Main Results:
- MMF enabled discontinuation of other medications in 4 patients and dose reduction in 15 (prednisone) and 9 (CsA).
- Significant reduction in mean prednisone dose (22.8 to 3.6 mg/m2/48h) in SD group (p=0.018).
- Significant reduction in mean CsA dose (4.3 to 2.9 mg/kg/24h) (p=0.008) and improved renal function (cystatin C decrease, p=0.007).
- Adverse events included abdominal pain (2 patients), GI upset (1), and CMV infection (1).
Conclusions:
- MMF demonstrates significant benefit in steroid-dependent NS patients.
- MMF facilitates reduction of steroid and CsA dosages in children with NS.
- MMF appears to be a safe and effective immunosuppressive option for pediatric NS, particularly for steroid-dependent cases.
Abstract:
The management of nephrotic syndrome (NS) in children remains a clinical challenge for pediatricians and pediatric nephrologists. Especially, the treatment of patients with steroid-resistant (SR) and steroid-dependent (SD) nephrotic syndrome, because they are at risk for developing complications from prolonged exposure to steroids, CsA and alkylating agents. Mycophenolate mofetil (MMF) is a selective and reversible inhibitor of inosine monophosphate dehydrogenase used above all in transplantology and recently also in patients with nephrotic syndrome. The aim of this study was to tentatively assess the usefulness and the safety of MMF as an immunosuppressive agent in children with steroid-resistant NS, in whom remission was not obtained with previous treatment regimens, and those with steroid-dependent NS, in whom severe adverse reactions were observed in steroid and cyclosporine therapy. The study included 19 children with NS (11 girls, 8 boys) aged 7 to 19.5 years (a mean of 13.5), treated at the Deptartment of Pediatric Nephrology. The duration of disease was from 1 to 16 years (a mean of 9.3). The patients were divided into 3 groups: I--9 children with steroid-dependent NS; II--6 children with steroid-dependent NS and episodes of steroid-resistance; III--4 children with steroid-resistant NS. All patients in groups II and III required multi-drug therapy (prednisone, cyclosporine A, methylprednisolone, chlorambucil, cyclophosphamide) before MMF was introduced. MMF was administered orally: 180-600 mg/m2 body surface/dose, twice daily. The follow-up period lasted for 4 to 16 months (a mean of 7.7). The clinical outcome analysis included decrease or disappearance of proteinuria, clinical improvement and/or possibility of tapering therapy intensity, especially the dosage of steroids and/or CsA. Also, renal function was monitored with serum cystatine C concentration. Particular attention was paid to adverse effects of MMF upon the gastro- intestinal tract and/or opportunistic infections. All medication (apart from MMF) could be discontinued in 4 patients; in 15 cases, prednizone dose was reduced and in 9 cases CsA dose was reduced or discontinued. In group I (SD) steroid treatment could be reduced from a mean prednisone dose of 22.8 to 3.6 mg/m2/48 hours (p=0.018), in groups II and III, in spite of 50 % reduction of a mean prednisone dose, the difference did not reach statistical significance. During MMF therapy Csa treatment could be reduced from a mean CsA dose 4.3 to 2.9 mg/kg/24 hours (p=0.008). Improvement or preservation of stable renal function was observed in all patients--cystatin C levels decreased significantly from a mean 1.35 to 0.96 mg/l (p=0.007). Adverse reaction to MMF (abdominal pain) was observed in 2 patients (nausea, vomiting, diarrhoea in 1, CMV infection in 1). The initial clinical observation of MMF treatment in nephrotic patients shows its best effect in the group of patients with steroid-dependent NS. MMF can safely be used in children with NS. The introduction of MMF allows for reduction of other chronically used medications, especially CsA and steroids.
