Remission of resistant MPGN type I with mycophenolate mofetil and steroids

Abstract

Very few studies have been published on how to treat children with membranoproliferative glomerulonephritis type I (MPGN I), and as yet there is only one report on the use of mycophenolate mofetil (MMF) in children with MPGN I. We report a 12-year-old boy who presented with edema, hypertension, nephrotic range proteinuria, and microscopic hematuria following an upper respiratory tract infection. Laboratory tests revealed a serum creatinine of 90 micromol/l, albumin of 20 g/l, and a C3 of 0.11 g/l (normal range: 0.7-1.4). Renal biopsy showed the presence of MPGN I. Upon failure to induce remission with prednisone, we started the patient on MMF at 500 mg/day (300 mg/m(2)), increasing up to a final dose of 2 g/day (1200 mg/m(2)), with a MMF metabolite mycophenolic acid (MPA) target range of 2-5 mg/l. Prednisone was subsequently reduced to alternate day therapy and gradually weaned to 7.5 mg on alternate days over 9 months. Within 4 months of starting MMF therapy, there was significant improvement in serum creatinine (decrease from 156 to 64 micromol/l), serum albumin (increase from 23 to 40 g/l), and proteinuria (decrease from 13 g/day to 40 mg/day). Twelve months following the introduction of MMF into his therapeutic regimen, he remains in remission with no further relapses. In summary, this case suggests that there may be potential benefit for use of MMF in children with refractory MPGN I, which supports the rationale for prospectively evaluating MMF treatment in a treatment trial of refractory MPGN I.

Paediatric use of mycophenolate mofetil

“…Table 1 summarizes published studies of MMF used for an unlicensed indication or off‐label in children under the age of 13 years. Some of these studies investigated the implications of pharmacokinetics and plasma concentrations of MPA on clinical outcome [14–16]. For example, the low AUC for MPA in the paediatric study by Dorresteijn et al .…”

Membranoproliferative glomerulonephritis

“…In idiopathic MPGN, preliminary studies suggest that the combination of MMF and corticosteroid can, in the short term, reduce proteinuria and may preserve renal function [28, 29]. …”

Membranoproliferative glomerulonephritis and C3 glomerulopathy in children: change in treatment modality? A report of a case series

“…Because of progressive proteinuria on PDN, MMF was started [ 25 ]. Daily proteinuria initially decreased from 4 to 2 g. However, impaired renal function and nephrotic-range proteinuria persisted with elevated alternative pathway activity.…”

“…Additional treatment consisted of prednisolone (PDN), in accordance with the dosage regimen for treatment of children with steroid-resistant nephrotic syndrome [ 41 , 42 ]. Further immunosuppressive treatment [cyclosporine A (CSA) and mycofenolate mofetile (MMF)] [ 25 , 42 ] was administered to patients who failed to attain partial or full remission of proteinuria. Eculizumab has been available in our hospital since 2013, but costs were not covered by all insurances, as this drug is still off-label for MPGN/C3G treatment.…”