Vanin-1 in Renal Pelvic Urine Reflects Kidney Injury in a Rat Model of Hydronephrosis

Abstract

Urinary tract obstruction and the subsequent development of hydronephrosis can cause kidney injuries, which results in chronic kidney disease. Although it is important to detect kidney injuries at an early stage, new biomarkers of hydronephrosis have not been identified. In this study, we examined whether vanin-1 could be a potential biomarker for hydronephrosis. Male Sprague-Dawley rats were subjected to unilateral ureteral obstruction (UUO). On day 7 after UUO, when the histopathological renal tubular injuries became obvious, the vanin-1 level in the renal pelvic urine was significantly higher than that in voided urine from sham-operated rats. Furthermore, vanin-1 remained at the same level until day 14. There was no significant difference in the serum vanin-1 level between sham-operated rats and rats with UUO. In the kidney tissue, the mRNA and protein expressions of vanin-1 significantly decreased, whereas there was increased expression of transforming growth factor (TGF)-β1 and Snail-1, which plays a pivotal role in the pathogenesis of renal fibrosis via epithelial-to-mesenchymal transition (EMT). These results suggest that vanin-1 in the renal pelvic urine is released from the renal tubular cells of UUO rats and reflects renal tubular injuries at an early stage. Urinary vanin-1 may serve as a candidate biomarker of renal tubular injury due to hydronephrosis.

Vanin 1: Its Physiological Function and Role in Diseases

“…This swelling of the kidney is caused by a build-up of urine, which in turn is caused by urinary tract obstruction. Hosohata et al [71] investigated the potential of vanin 1 as a biomarker in a unilateral ureteral obstruction (UUO) rat model, which is also used to develop renal fibrosis in mice and rats. On day 7 after UUO, urinary vanin 1 levels were significantly higher than those in urine from sham-operated rats, suggesting a potential cleavage of vanin 1 from the membrane or a higher expression of its soluble form.…”

Mechanism of Albuminuria Reduction by Chymase Inhibition in Diabetic Mice

“…The sections were mounted on adhesive glass slides (Matsunami Glass Ind., Kishiwada, Japan) and deparaffinized with lemosol (Wako Pure Chemicals, Osaka, Japan). The glomerulus histological change was assessed using PAS staining [ 48 ]. Mast cells were stained with 0.05% toluidine blue (Chroma-Gesellschaft, Stuttgart, Germany) [ 47 ].…”

“…Immunohistological examinations were performed using an anti-nephrin antibody (LS-B1382, LSBio, Seattle, WA, USA) and anti-MMCP-4 antibody (ab92368, Abcam, Cambridge, UK) according to a protocol described elsewhere [ 48 ]. In brief, to suppress endogenous peroxidase activity and nonspecific binding, the deparaffinized sections were incubated with 3% hydrogen peroxide and protein-blocking solution for 5 min at room temperature, respectively.…”

Roles Played by Biomarkers of Kidney Injury in Patients with Upper Urinary Tract Obstruction

“…Vanin-1 in cellular membranes is anchored to glycosylphosphatidylinositol. The anchor may be cleaved and soluble vanin-1 then secreted or released into the extracellular matrix in response to various stimuli [ 102 ].…”

“…Urine vanin-1 levels are increased in patients with drug-induced AKI [ 103 ] and UUTO [ 23 ], and in rat models with high salt-induced kidney damage [ 104 ], diabetic nephropathy [ 105 ], and UUTO [ 102 ]. UUTO inhibits urine flow and increases intratubular pressure, causing renal tubular damage.…”