Long-term mizoribine intermittent pulse therapy, but not azathioprine therapy, attenuated histologic progression in a patient with severe lupus nephritis

Sir, – Mizoribine (MZR) is 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 (MMF). We previously reported the efficacy and safety of a new MZR treatment regimen, namely, oral MZR intermittent pulse therapy, which we considered to 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 [Tanaka et al. 2003, 2005, 2006]. In an experimental setting, MZR has been reported to attenuate tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction via suppression of infiltration of the interstitium by macrophages [Sato et al. 2001]. We encountered a Japanese adolescent with severe lupus nephritis (WHO Class IV-G), in whom posttreatment renal biopsy confirmed marked attenuation of histologic progression following long-term intermittent MZR pulse therapy. Based on the records of sequential renal biopsies and of the clinical course available to us of our patient, we found that the previously administered treatment with azathioprine (AZP), prior to the start of the MZR pulse regimen, did suppress the lupus activity, but could not attenuate the histologic progression of the disease in our patient. This letter might lend further support, from the histologic standpoint, to the efficacy of long-term MZR intermittent pulse therapy for selected patients with severe lupus nephritis. Case report