Abstract: Objective  To explore the diagnosis and differential diagnosis of IgA nephropathy. Methods  The clinical data of 2 children with IgA nephropathy were retrospectively analyzed. The pertinent literatures were reviewed. Results  In 2 males aged 6 and 7 years, the clinical features were a large amount of proteinuria (mainly albumin), low serum albumin, high cholesterol, and persistent microscopic hematuria, which were in line with the diagnosis of nephrotic syndrome. The effects of hormone and immunosuppressive therapy were poor. Renal pathology immunofluorescence and light microscopy findings were in accord with mild to moderate mesangial proliferative IgA nephropathy (M1E0S0T0). Electron microscope showed glomerular basement membrane lesions (layering, breakage, and uneven thickness), which could not exclude Alport syndrome. Further gene detection confirmed a pathogenic mutation of COL4A5. Conclusions  It is rare that IgA nephropathy is combined IgA nephropathy at the same time. Attention should by paid to those who had a poor effect of treatment or had a related family history in IgA patients because it is possible that IgA nephropathy and IgA nephropathy may occurred at the same time.