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Purpose: The present study aims to explore the effects of tacrolimus on proteinuria in patients with idiopathic membranous nephropathy (IMN) and recommend an appropriate dosage schedule via machine learning method., Methods: The E max model was constructed to analyze the effects of tacrolimus on proteinuria in patients with IMN. Data were mined from published literature and machine learning was built up with E max model, among which the efficacy indicator was proteinuria change rates from baseline. 463 IMN patients were included for modeling, and tacrolimus therapeutic window concentrations were 4-10 ng/ml., Results: In machine learning model, the E max from tacrolimus effecting proteinuria in IMN patients was -72.7%, the ET 50 was 0.43 months, and the time to achieving 25% E max , 50% E max , 75% E max , and 80% (plateau) E max of tacrolimus on proteinuria in patients with IMN were 0.15, 0.43, 1.29, and 1.72 months, respectively., Conclusion: For achieving better therapeutic effects from tacrolimus on proteinuria in patients with IMN, tacrolimus concentration range need to be maintained at 4-10 ng/ml for at least 1.72 months., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

BACKGROUND Universal agreement about the optimum therapeutic approach for adults with nephrotic syndrome caused by idiopathic membranous nephropathy (IMN) is lacking. OBJECTIVE To establish the long-term outcomes of a 6-month course of steroids and cyclophosphamide in patients with IMN and nephrotic syndrome. DESIGN Patients aged >16 years who had nephrotic syndrome (proteinuria >3.5g/day, or proteinuria ≥2.5g/day accompanied by serum albumin <25g/I [<2.5g/dl], edema and hyperlipidemia) caused by biopsy-confirmed IMN of ≥6 months' duration were recruited for this prospective, open-label single-center Indian study. Exclusion criteria included malignancy and renal vein thrombosis. INTERVENTION Participants were randomized to receive supportive therapy (diuretics, antihypertensive agents and restriction of sodium intake) or a 6- month course of alternating months of treatment with steroids (intravenous methylprednisolone 1g/day for 3 days followed by oral prednisolone 0.5 mg/kg/day for 27 days) and oral cyclophosphamide 2 mg/kg/day. Administration of angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers was not permitted in the first year of the study. Patients assigned to supportive therapy were permitted to switch to steroid-cyclophosphamide treatment 2 years after randomization. Follow-up continued for ≥10 years and analysis was by intention to treat. OUTCOME MEASURES The main end points were doubling of serum creatinine level, progression to end-stage renal disease (ESRD), and death. RESULTS Of the 104 patients who were enrolled between March 1993 and February 1995, 93 completed the study (46 in the supportive therapy group; 47 in the steroid-cyclophosphamide group). Demographic and laboratory characteristics were similar in the two groups at baseline. Compared with patients assigned to supportive therapy, patients assigned to steroid-cyclophosphamide treatment had higher rates of 10-year dialysis-free survival (89% vs 65%; P=0.016), 10-year survival free of any end point (79% vs 44%; P=0.0006) and remission ([reduction of proteinuria to <2g/day or to 50% of baseline] 72% vs 35%; P<0.0001). Among the patients who achieved remission, relapses occurred in 4 of 16 (25%) of those assigned to supportive therapy and 8 of 34 (24%) of those assigned to steroid-cyclophosphamide treatment. Of the 15 patients assigned to supportive therapy who switched to cyclophosphamide-steroid treatment, 7 (47%) achieved remission. At 10 years, the steroid-cyclophosphamide group had a lower prevalence of hypertension, edema and hypercholesterolemia, and a higher mean quality of life visual analog scale score, than did the supportive therapy group (P<0.01 for all). The most frequent complication was infection, which occurred in 11 patients randomized to supportive therapy and 7 patients randomized to steroid-cyclophosphamide treatment. CONCLUSION A 6-month course of cyclophosphamide and steroids produces better long-term outcomes than does supportive therapy in patients with nephrotic syndrome caused by IMN. [ABSTRACT FROM AUTHOR]

The studies of idiopathic membranous nephropathy (IMN) require sufficiently long duration of follow-up to understand the effect of treatment on the development of end-stage renal disease (ESRD) in IMN. The aim was to assess the remission rates with steroids and cyclophosphamide regimen for IMN at the end of 10 years of follow-up. A prospective, open-label study performed in Nephrology department of a state run tertiary care centre in a southern state of India. Adult (age >18 years) patients with biopsy-proven IMN of at least 6-month duration were included in the study. Patients received a 6-month course of alternate months of steroid and cyclophosphamide. The patients were followed for 10 years. Study end points were doubling of serum creatinine, development of ESRD, or death. A total of 58 IMN patients were recruited from 1997 to 2001. Out of 58 patients included, only 48 patients could complete the treatment schedule in six months. The remission rate at the end of 10 years was 58.6% (34 in 58 patients). The probability of dialysis-free survival in our study was 89.6% at the end of 10 years follow-up. The regimen of steroids and cyclophosphamide in IMN had a remission rates not as high as reported before. It was associated with high relapse rates and more infections.