Safety and efficacy of prednisolone, mizoribine and lisinopril combination therapy for severe childhood IgA Nephropathy

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Abstract
Background Angiotensin-converting enzyme inhibitors such as lisinopril have long been used for childhood IgA Nephropathy (cIgAN). A two-year combined regimen including prednisolone + mizoribine + warfarin + dipyridamole was shown in our previous randomized control trial to be better for severe cIgAN than prednisolone + mizoribine (without warfarin or dipyridamole) in proteinuria remission. However, to avoid warfarin nephropathy and to shorten the duration of prednisolone use, we consider a new two-year combined regimen of prednisolone + mizoribine + lisinopril. Methods Between July 1976 and December 2022, among 567 biopsy-proven cases of cIgAN, there were 93 cases of severe cIgAN treated with prednisolone + mizoribine. We investigated clinicopathological differences between the 77 cases of cIgAN (82.8%) with the previous treatment and the other 16 patients with the new treatment regimen. After 1:1 propensity score matching was performed to account for between-group differences (amount of proteinuria, eGFR, and the percentage of patients with C0, C1, and C2), we analyzed 15 matched pairs. Results Clinicopathological presentations did not significantly differ between the groups. Kaplan-Meier analysis of proteinuria remission showed that the patients with the new treatment achieved significantly higher (90.0 vs. 64.1% at 11 yrs, p = 0.01), and faster (1.0 vs. 4.0 yrs, p = 0.03) proteinuria remission than those with the previous treatment. Proteinuria recurrence was not significantly different between the groups. Conclusions We suggested the superiority of 2-year combined regimen of prednisolone + mizoribine + lisinopril for severe cIgAN in achieving early proteinuria remission and shortening prednisolone use without recurrence of proteinuria.

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