Background <p>Idiopathic nephrotic syndrome (INS) is a significant kidney disorder in pediatrics. Early diagnosis of minimal change disease (MCD) is difficult in children with nephrotic syndrome (NS). Angiopoietin-like protein 4 (ANGPTL4), found on the surface of podocytes, has been linked to nephrotic syndrome (NS) and plays a role in triggering proteinuria. Macrophage migration inhibitory factor (MIF) functions as a crucial modulator of the innate immune system and partly counteracts glucocorticoid-induced immune system inhibition. This study aimed to assess the role of ANGPTL4 and MIF as biomarkers in steroid responsiveness of INS.</p> Methods <p>This cross-sectional comparative study involved 70 children with NS and 40 healthy children as a control group.</p> Results <p>Urinary MIF/creatinine levels were significantly elevated in steroid-resistant nephrotic syndrome (SRNS) relative to in steroid-sensitive nephrotic syndrome (SSNS) and controls (<i>p</i> &lt; 0.001). However, ANGPTL4 levels were significantly elevated in the SSNS group relative to the SRNS and control groups (<i>p</i> &lt; 0.001). Regarding plasma MIF and urinary MIF/creatinine levels, there were no significant differences between MCD and FSGS, whereas ANGPTL4 levels were significantly elevated in MCD relative to FSGS (<i>p</i> &lt; 0.001).</p> Conclusions <p>Elevated levels of serum and urinary MIF levels were consistent with SRNS. Furthermore, ANGPTL4 was found to be highly upregulated in SSNS, unlike SRNS, which serves as a potential marker to distinguish between these two diseases.</p> Graphical abstract <p></p>