Hormonal and molecular characterization of calcium oxalate stone formers predicting occurrence and recurrence

Abstract

The purpose of the study is to investigate the role of sex hormones, androgen receptors (ARs) and miRNA/CSF-1 in occurrence and recurrence of calcium oxalate (CaOx) renal urolithiasis. In this prospective study, 74 patients with CaOx stones; stone formers group (SFG) and 40 healthy subjects; control group were compared. SFG includes both de novo and recurrent cases. Steroid sex hormone plasma assay including testosterone, free testosterone, dihydrotestosterone, estradiol, and sex hormone binding globulin was analyzed. ARs, miRNA-185-5p and CSF-1 expression were compared between the groups. SFG showed significant higher ARs and miRNA-185-5p expression (3.7 ± 1.3, 1.8 ± 0.4, respectively) than control group (1 ± 0.08 and 1 ± 0.07, respectively) (p < 0.05). However, CSF-1 expression was significantly lower in stone formers than control group (0.4 ± 0.19 vs 1 ± 0.1, respectively) (p < 0.05). No differences were detected between de novo and recurrent SFG regarding sex hormones, AR, miRNA or CSF-1 expression. Our data suggest the important role of AR, miRNA and CSF-1 signaling in human nephrolithiasis pathogenesis.

Establishment and application of a nomogram diagram for predicting calcium oxalate stones in patients with urinary tract stones

“…However, CSF-1 expression was significantly lower in the stone group than in the healthy subjects. Wei Zhu et al showed that inhibition of androgen receptor (AR) expression in renal tubular epithelial cells increased macrophage recruitment/M2 polarization, which resulted in enhanced phagocytosis of CaOx crystals in the kidney, confirming that estrogens inhibit the formation of stones more than androgens do in the human body [ 23 , 24 ].…”

Establishment and application of a nomogram diagram for predicting calcium oxalate stones in patients with urinary tract stones

“…However, CSF-1 expression was signi cantly lower in the stone group than in the healthy subjects. Wei Zhu et al showed that inhibition of androgen receptor (AR) expression in renal tubular epithelial cells increased macrophage recruitment/M2 polarization, which resulted in enhanced phagocytosis of CaOx crystals in the kidney, con rming that estrogens inhibit the formation of stones more than androgens do in the human body (23,24).…”

Non-Coding RNAs in Kidney Stones

“…AR can decrease Mp colony-stimulating factor 1 (CSF-1) expression by increasing miRNA-185-5p expression to suppress M2 Mp polarization-mediated intrarenal CaOx crystal phagocytosis [72]. In a prospective study, Elshal et al found that patients (n = 74) with CaOx stones had a higher expression of ARs and miRNA-185-5p compared with healthy individuals (n = 40), while CSF-1 expression was lower in stone formers [73]. These findings suggest that the signaling pathways of AR, miRNA, and CSF-1 are significant factors in the development of kidney stones.…”

“…Some non-coding RNAs have altered expression profiles in kidney stones and may have the potential as biomarkers to aid in the diagnosis of kidney stones and to assess the extent of kidney damage and recovery after treatment [23,24,73,94]. However, none of the non-coding RNAs are currently used as routine tests for kidney stone patients.…”

“…For example, miR-223-3p was more highly expressed in urinary small Extracellular Vesicles (sEVs) from CaOx stone patients [24]. In a prospective investigation using plasma samples, miRNA-185-5p expression was significantly higher in patients with CaOx stones (n = 74) than in healthy subjects (n = 40) [73]. Five miRNAs (miR-6796-3p, miR-30d-5p, miR-3192-3p, miR-518b, and miR-6776-3p) and six lncRNAs (lnc-TIGD1L2-3, lnc-KIN-1, lnc-FAM72B-4, lnc-EVI5L-1, lnc-SERPINI1-2, and lnc-MB-6) were differentially expressed in both CaOx patients' urine and NaOx-induced HK-2 cells [23].…”