Background: Cyclophosphamide (CTX) and cyclosporine (CsA) are used in idiopathic membranous nephropathy (IMN); however, limited data comparing their efficacy are available. We aimed to determine the baseline clinicopathological predictive factors of renal outcome in patients with IMN who received CTX or CsA. We also attempted to establish simple risk scores for predicting renal outcomes in IMN patients prescribed CsA-based initial treatment. Method: We retrospectively included 516 patients with biopsy-proven IMN from January 1, 2007 to October 31, 2019. The primary outcome was no remission and a decline of renal function in IMN patients who received CTX and CsA as initial treatment. Results: The CsA group showed higher complete remission (CR) rate at 6 months, and no significant difference in accumulative total remission between the two groups was observed in the initial 12 months. Independent predictors of primary outcomes were urine protein content and serum albumin in the CTX-based group and serum creatinine, triglyceride, and focal segmental glomerulosclerosis (FSGS) lesions in the CsA-based treatment group. The area under the receiver operating characteristic curve based on a three-variable risk score in predicting primary outcome was 0.791 (95% CI 0.720–0.862). IMN patients with FSGS lesions who received CsA-based initial treatment had a higher percentage of primary outcome and a lower CR rate. Conclusion: Serum creatinine, hypertriglyceridemia, and FSGS lesions were important predictors of a worse prognosis in CsA-based initial treatment patients. Our simple risk score was able to predict renal outcomes in IMN patients receiving CsA-based initial treatment with good discrimination. Name of the registry: Chinese Clinical TrialRegistry Trial registration number: ChiCTR2200059658 May 5, 2022 Retrospectively registered URL of trial registry record: https://www.chictr.org.cn/hvshowproject.aspx?id=168696
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