The successful treatment of rapidly progressive idiopathic membranoproliferative glomerulo-nephritis Type 1 in a 4-year-old male pediatric patient.

A multivariate analysis [4] revealed that the presence of crescent formation on initial biopsy irrespective of type of membranoproliferative glomerulonephritis (MPGN) was independently associated not only with end-stage renal disease but also with post-transplantation recurrence. In this study, we reported on a 4-year-old male pediatric patient requiring hemodialysis due to rapidly progressive idiopathic MPGN Type 1 with severe nephrotic syndrome and extensive cellular crescent formation on initial biopsy. The patient had been treated intravenously (i.v.) with 9 pulses of methylprednisolone, followed by daily prednisolone, resulting in the withdrawal of dialysis within 1 month. However, since active lesions in the second renal biopsy such as cellular crescents still remained and nephrotic range proteinuria had persisted for more than 2 months, the patient received additional 3 i.v. pulses of methylprednisolone, followed by combinations of alternate-day prednisolone, mizoribine, dipyridamole and warfarin, which lead to complete remission in a short-period of time. The patient has been off the combination therapy for 10 months because the third biopsy prior to the termination of this regimen showed decreased inflammatory activity. There is currently no established protocol for children with crescentic MPGN due to a rarity of its clinicopathological presentation. This case report indicates that early treatment with multiple pulses of methylprednisolone followed by the short-term combination therapy may be of benefit for children with rapidly progressive idiopathic MPGN Type 1, even when both diffuse crescentic changes and nephrotic syndrome are present at onset.

Mycophenolate mofetil therapy for childhood-onset steroid dependent nephrotic syndrome after long-term cyclosporine: extended experience in a single center.

BACKGROUND: Mycophenolate mofetil (MMF) is being used increasingly in children with steroid-dependent nephrotic syndrome (SDNS). However, there is limited information on the optimal therapeutic range for mycophenolic acid (MPA), the active metabolite of MMF, in these patients. METHODS: 26 patients with SDNS (mean age 13.1 years, 19 with minimal change disease and 7 with focal segmental glomerulosclerosis) who had received MMF for at least 6 months after longterm cyclosporine (CsA, mean 56 months) at Saitama Children's Medical Center between September 2002 and August 2008 were analyzed. MMF was introduced at an initial dose of 250 mg/12 h, adjusted to maintain target predose MPA at greater than 2 microg/ml (maximum 1 g twice daily) gradually over 4 weeks. After the introduction of MMF, the dosages of both CsA and prednisolone (PSL) were tapered off if possible. RESULTS: The mean MMF dose required was 34 +/- 6 mg/kg, which maintained the mean predose MPA levels of 3.1 mg/ml. In 26 patients, treatment with MMF for a mean follow-up period of 19 months (range 7 - 42), resulted in a reduction of the mean PSL dose from 0.33 +/- 0.23 to 0.17 +/- 0.11 mg/kg per day (p < 0.01) and mean CsA dose from 3.2 +/- 1.7 to 1.3 +/- 1.8 mg/kg per day (p < 0.01). The mean 12-monthly relapse rates decreased from 2.5 +/- 1.4 to 0.8 +/- 1.2 episodes (p < 0.01). In 20 patients treated with MMF (77%), the dose of PSL and/or CsA was successfully tapered with a reduction in the relapse rates. In 6 patients, however, CsA therapy was reintroduced or its dose was increased because of treatment failure. The patients whose average predose MPA levels were less than 3 microg/ml were significantly likely to have treatment failure (p < 0.05). 2 patients reduced the MMF dosage because of anemia or herpes labialis. However, no severe gastrointestinal discomfort was seen in any patients. Despite long-term CsA therapy, marked tubulointerstitial fibrosis developed during MMF therapy in surveillance biopsies of only one of these five patients. CONCLUSIONS: Therapy with MMF based on the predose MPA levels can be a less toxic alternative to CsA or in some cases a useful additional medication to allow for a reduction in the CsA and/or PSL dosage.