Long‐term intermittent pulse therapy with mizoribine attenuates histologic progression in young patients with severe lupus nephritis: Report of two patients (Brief Communication)

Abstract

Mizoribine (MZR), a novel selective inhibitor of inosine monophosphate dehydrogenase in the de novo pathway, whose mode of action is very similar to that of mycophenolate mofetil, has been successfully applied without serious adverse effects for the treatment of renal diseases. We have previously reported the efficacy and safety of a new MZR treatment regimen, namely, oral MZR intermittent pulse therapy, which we examined based on the observation that it might show superior efficacy to the conventional daily low-dose MZR regimen on account of the higher peak serum MZR levels, in selected patients with lupus nephritis. Two Japanese patients with severe lupus nephritis (WHO class IV-G) who were administered long-term intermittent MZR pulse therapy, and in whom pre- and post-treatment renal biopsies were reported. Post-treatment renal biopsy confirmed the marked attenuation of histologic progression by the treatment. These clinical observations may lend further support, from the histologic standpoint, to the efficacy of long-term MZR intermittent pulse therapy for selected patients with active lupus nephritis.

Mizoribine Treatment of Young Patients with Severe Lupus Nephritis: A Clinicopathologic Study by the Tohoku Pediatric Study Group

“…Our results suggested that this new treatment protocol may be beneficial and may have a higher efficacy and lower toxicity than the conventional protocol of low-dose (3–4 mg/kg) daily administration of MZR (MZR-C) [9, 10]. Moreover, we recently confirmed that our MZR-P protocol may attenuate histological progression in selected patients with DPLN [11, 12], similar to the results obtained in previously reported pediatric cases receiving long-term iv-CPA [3]. …”

Mizoribine selectively attenuates monocyte chemoattractant protein‐1 production in cultured human glomerular mesangial cell: A possible benefit of its use in the treatment of lupus nephritis

“…Since the inflamed glomeruli express 14‐3‐3 proteins and heat shock protein 60, which are known to be MZR‐binding proteins, MZR may directly interact with inflamed glomerular cells, because MZR is directly excreted unchanged into the urine . Clinically, we previously reported that post‐treatment renal biopsy specimen from patients with proliferative lupus nephritis treated with MZR, showed marked attenuation of glomerular and interstitial lesions, and significantly reduced the number of infiltrated macropharges . Ikezumi et al .…”

“…1 Clinically, MZR has been successfully used without any serious adverse effects for the long-term treatment of young patients with lupus nephritis. [1][2][3] Besides its immunosuppressive effects, MZR has recently been reported to suppress the progression of histologic chronicity in selected patients with lupus nephritis and immunoglobulin A (IgA) nephropathy. [1][2][3][4] Moreover, some experimental reports described that MZR attenuates tubulointerstitial fibrosis in rat models of unilateral ureteral obstruction, non-insulindependent diabetes and peritoneal fibrosis via suppression of macrophage infiltration of the interstitium.…”

“…Mizoribine (MZR) is a selective inhibitor of the inosine monophosphate dehydrogenase – a key enzyme in the de novo pathway of guanine nucleotides – that was developed in Japan . Clinically, MZR has been successfully used without any serious adverse effects for the long‐term treatment of young patients with lupus nephritis . Besides its immunosuppressive effects, MZR has recently been reported to suppress the progression of histologic chronicity in selected patients with lupus nephritis and immunoglobulin A (IgA) nephropathy .…”

Non-Infectious Pediatric Uveitis

“…[113] Mizoribine has been developed in Japan and has been shown to be a potent immunosuppressant in children with relapsing corticosteroid-dependent nephritic syndrome. [115][116][117] Side effects have been reported as a mild transient hyperuricemia. [114] There has also been a case report of its successful use in JRA, childhood renal sarcoidosis, and young patients with lupus nephritis.…”