In this study, we designed a prospective, open-label randomized trial to compare the effect of preprandial once-a-day administration of CyA with that of conventional twice-a-day administration for IMN with associated SRNS. Blood CyA concentrations

at C0 and C2 were also evaluated during treatment. Methods This study was C59 wnt molecular weight registered at the University Hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR) under trial identification no. UMIN C000000369 and was approved by the Clinical Study Review Board at Fukuoka University Hospital (approval no. 03-129). The study was conducted in accordance with the principles of the declaration of Helsinki. Written informed consent was obtained before patient enrollment and after a thorough explanation of the trial’s objectives, duration, and structure. The availability of alternative drugs, the possibility of adverse reactions, privacy measures, and the voluntary nature of the trial, including the right to withdraw without repercussions, were all carefully explained. The institutional review boards at the collaborating institutions also approved the protocol when requested. Patients

SRNS patients (age 16–75 years) with IMN diagnosed by renal biopsy were enrolled through computerized registration from kidney centers in Japan between 2004 and 2007. Membranous nephropathy secondary to systemic diseases, e.g., diabetic nephropathy and collagen diseases, were excluded at registration. Nephrotic see more syndrome (NS) was defined according to the standard criteria in Japan acetylcholine [3]—(1) urine protein (UP) excretion >3.5 g/day; (2) serum albumin <3.0 g/dL or serum total protein <6.0 g/dL; (3) presence of edema; and (4) total cholesterol >250 mg/dL. At least the first and second criteria were necessary for the diagnosis. SRNS was determined when patients did not achieve complete remission (CR) or incomplete remission (ICR) 1 (as described in ‘Clinical assessment’ section) after 4 weeks of prednisolone (PSL) therapy at 40–60 mg/day. The inclusion and exclusion criteria are listed in Table 1. Table 1 Inclusion and exclusion criteria Inclusion criteria  1. Age between 16 and 75 years  2. UP >3.5 g/day and serum albumin

level <3.0 g/dL  3. PSLalone treatment for >4 weeks did not decrease UP into <1 g/day  4. Membranous nephropathy was diagnosed by renal biopsy.  5. No history of treatment with CyA-MEPC before registration  6. Informed consent form voluntarily signed by the participant Exclusion criteria  1. Patients with creatinine clearance <50 mL/min or serum creatinine >2 mg/dL  2. Patients that received other immunosuppressants within 1 month before the study commencement  3. Patients treated with nephrotoxic and hyperkalemic Smad3 phosphorylation agents during the study period  4. Patients with a malignant tumor or a history of a recurrent malignant tumor  5. Patients with hypertension uncontrolled with antihypertensive drugs  6. Patients with malabsorption syndrome, cerebral dysfunction, or epilepsy  7.