Abstract: Objective To explore the relationship between IgA nephropathy S1 with podocyte hypertrophy or apical lesions and glucocorticoid reactivity and compare clinical efficacy of MMF plus small-dose glucocorticoid with tacrolimus alone in patients with glucocorticoid-resistant IgAN and S1 with podocyte hypertrophy or apical lesions. Methods From 2015 to 2020, 52 patients of primary IgAN and 21 subjects with glucocorticoid-resistant IgAN and S1 with podocyte hypertrophy or apical lesions were reviewed with regards to glucocorticoid therapy sensitivity and pathological typing. The differences in clinical biochemical parameters,adverse events and prognoses were recorded. Results Pathological type was S1 with podocyte hypertrophy or apical lesions rather than patients with non-S1 with podocyte hypertrophy or apical lesions were more prone to be glucocorticoid-resistant. In glucocorticoid-resistant IgAN patients of pathological type S1 with podocyte hypertrophy or apical lesions, tacrolimus alone improved proteinuria level and better stabilized renal function(three months:67.49±25.81 vs 36.30±63.06, P=0.039; six months:77.15±16.06 vs 40.19±30.39, P=0.012). However, no significant inter-group difference existed in the levels of serum albumin and hemoglobin. Conclusion IgAN patients with podocyte hypertrophy or apical lesions are more prone to be glucocorticoid-resistant. For glucocorticoidresistant IgAN patients of S1 with podocyte hypertrophy/apical lesions, tacrolimus is significantly superior in relieving proteinuria to MMF plus low-dose glucocorticoid.