Analysis of microRNA expression in patients with uric acid calculi

Uric acid calculi (UAC) account for about 10% of cases worldwide, although this varies among countries. The etiology of nephrolithiasis is multifactorial, involving both genetic and environmental factors. Kidney stones occur three times more frequently in individuals with a family history of the condition compared to those without such a history. Genetic factors also contribute to cases of UAC. Genes such as ZNF365, SLC2A9 and SLC22A12 may be associated with the development of uric acid stones. MicroRNAs (miRNAs) are small RNA molecules, that play a significant role in regulating gene expression. The aim of this study was to characterize the expression profile of miRNAs associated with the SLC2A9, SLC22A12 and ZNF365 genes in patients with uric lithiasis. Twenty-two patients with pure uric stones and 8 controls with no history of lithiasis were included, all of whom consented voluntarily. To analyze the gene expression levels of the microRNAs studied, total RNA was obtained using the miRVana^®miRNA kit, following the manufacturer's guidelines. qPCR analyses were then carried out using specific probes for the selected microRNAs. When comparing clinical characteristics, patients with nephrolithiasis had significant hyperuricemia (p < 0.0001) and more acidic urine (p = 0.0012). Lower urinary citrate excretion was also observed in patients with nephrolithiasis (p = 0.0047). With regard to microRNA expression data, statistically significant under-expression was observed in patients with calculi of microRNAs 143-3p (p = 0.015), 4770 (p = 0.0194), 4750-3p (p = 0.037), 301b-5p (p = < 0.0001) and 9-5p (p = 0.0015). In addition, microRNAs 4770 and 4750-3p were underexpressed in individuals with multiple stones (p = 0.0197, p = 0.0023 respectively). In relation to miR-4750-3p, it was also overexpressed in cases with stones larger than 2 cm (p = 0.0557). With the results of our study, we can conclude that the microRNAs 143-3p, 4770, 4750-3p, 301b-5p and 9-5p may be associated with the development of uric lithiasis. In addition, under-expression of microRNAs 4770 and 4750-3p is associated with the occurrence of multiple stones, while over-expression of miR-4750-3p is related to the formation of stones larger than 2 cm.