Losartan Monotherapy vs Combination Regimens in IgA Nephropathy: A Systematic Review and Network Meta-analysis

Background: IgA nephropathy (IgAN) is a disorder in which Immunoglobulin A (IgA) antibodies build up, causing kidney damage. Losartan, an Angiotensin Receptor Blocker (ARB), has shown promise in patients with IgAN. However, a comparison of losartan with other IgAN therapies is missing. This study investigates the efficacy of losartan compared to different regimens. Methods: A systematic search of four electronic databases was conducted till January 2025. The study was registered in PROSPERO (CRD42025634499). Risk of bias assessment was performed using the ROB-2 tool. Results: The study included five RCTs in the quantitative analysis. Although losartan + temocapril ranked first in systolic blood pressure (SBP) and diastolic blood pressure (DBP) reductions at 12 months [surface under the cumulative ranking curve (SUCRA) = 97% and 86%, respectively], pairwise comparisons versus losartan were not statistically significant, so clinical superiority is uncertain. Additionally, compared to temocapril, losartan + temocapril and losartan demonstrated statistically significant reductions in SBP at 12 months. Regarding proteinuria reduction, none of the interventions demonstrated a statistically significant difference compared to losartan at 3 and 6 months. However, mizoribine and mizoribine + losartan showed a statistically significantly greater reduction in proteinuria than losartan at 12 months. Conclusions: Among patients with IgAN from East Asian cohorts, mizoribine and mizoribine + losartan best reduced proteinuria at 12 months. Regarding BP, losartan + temocapril best reduced SBP and DBP at 12 months. However, clinical superiority is uncertain, and estimates were imprecise due to limited power.