MicroRNAs in idiopathic childhood nephrotic syndrome.

Background: miRNAs are non-coding RNA that are recognized as biomarkers of kidney disorders. There is limited information on the differential expression of miRNA and their target genes in idiopathic nephrotic syndrome of childhood.

Methods: We enrolled patients, 2-18 years old, with steroid-sensitive nephrotic syndrome, either at onset or during relapse, and steroid-resistant disease, at diagnosis of steroid-resistance. Patients with steroid-sensitive disease were off immunosuppressive medications, while those with steroid-resistance were on therapy with prednisolone at enrollment. Controls were healthy children attending the hospital for vaccinations or for minor non-infectious, non-kidney ailments. Following RNA extraction from whole blood, differential expression of 2549 miRNAs was examined to identify differentially expressed miRNA, defined as those with absolute log₂ fold change > 2 and adjusted P < 0.05. Target genes, predicted using miRNet, were compared against the genes for nephrotic syndrome in the NCBI database, and the ontology of selected genes was examined using DAVID.

Results: Comparison of miRNA expression in 36 patients and 12 controls led to the identification of 62 and 12 differentially expressed miRNA in patients with steroid-sensitive and steroid-resistant disease, respectively. Of 76 miRNAs that were differentially regulated between the two disease categories, 26 were unique to steroid-sensitive disease and 11 to steroid-resistance. Of 5955 and 2813 genes targeted by the miRNAs specific to steroid-sensitive and steroid-resistant nephrotic syndrome, respectively, 79 were relevant in context of the disease.

Conclusion: Steroid-sensitive and steroid-resistant nephrotic syndrome have distinct miRNA expression profiles, which can be examined as biomarkers and in pathogenetic pathways.