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Abstract: Objective To investigate the relationship between the interaction of microRNA-146a-5p (miR-146a-5p) and microRNA-21 ( miR-21) and its effect on the risk and severity ofprimary nephrotic syndrome (NS). Methods A total of 103 patients with NS from August 2021 toAugust 2023 were selected as the study group, and another 103 healthy volunteers who underwent physical examination during the same period were selected as the control group. Compare the different pathological types [minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS)] and the degree of renal injury in the two groups, and study the relative expression levels of serum miR-146a-5p and miR-21 in patients. Analyze the diagnostic value and interactive effects of miR-146a-5p and miR-21 on NS, and further analyze the correlationbetween miR-146a-5p, miR-21, and disease severity. Results The relative expression level ofmiR-146a-5p in the study group was lower than that in the control group, and the relative expressionlevel of miR-21 was higher than that in the control group (P < 0. 05). The relative expression levels of serum miR-146a-5p and miR-21 in patients with different pathological types or different degrees ofrenal injury in the study group showed significant differences (both P< 0. 05). The AUC of the combined diagnosis of NS by miR-146a-5p and miR-21 was 0. 923 (95 % CI: 0. 877 - 0. 955), thesensitivity was 78. 64 % , and the specificity was 90. 29 % , which were significantly better than those of miR-146a-5p and miR-21 alone. The optimal cut-off value was used to divide miR-146a-5p and miR-21 into high expression group and low expression group. The low expression of miR-146a-5p and high expression of miR-21 had a positive interaction on the risk of NS development, which was a sub-multiplication model. miR-146a-5p was negatively correlated with NS pathological types andthe degree of kidney injury (r = - 0. 613, - 0. 657, P< 0. 05), while miR-21 was positively correlated with NS pathological types and the degree of kidney injury (r = 0. 664, 0. 702, P< 0. 05). Conclusion The abnormal expression of miR-146a-5p and miR-21 in the serum of NS patients isassociated with the degree of kidney injury in patients. In addition, miR-146a-5p and miR-21 have a positive interactive effect on the risk of NS, and their simultaneous exposure can increase the risk of NS.

Key words: miR-146a-5p, miR-21, interaction, primary nephrotic syndrome, kidney function