Abstract
Acute crystalline nephropathy is closely related to tubulointerstitial injury, but few studies have investigated glomerular changes in this condition. Thus, in the current study, we investigated the factors involved in glomerular and tubulointerstitial injury in an experimental model of crystalline-induced acute kidney injury (AKI). We treated male Wistar rats with a single injection of sodium oxalate (NaOx, 7 mg⋅100 g–1⋅day–1, resuspended in 0.9% NaCl solution, i.p.) or vehicle (control). After 24 h of treatment, food and water intake, urine output, body weight gain, and renal function were evaluated. Renal tissue was used for the morphological studies, quantitative PCR and protein expression studies. Our results revealed that NaOx treatment did not change metabolic or electrolyte and water intake parameters or urine output. However, the treated group exhibited tubular calcium oxalate (CaOx) crystals excretion, followed by a decline in kidney function demonstrated along with glomerular injury, which was confirmed by increased plasma creatinine and urea concentrations, increased glomerular desmin immunostaining, nephrin mRNA expression and decreased WT1 immunofluorescence. Furthermore, NaOx treatment resulted in tubulointerstitial injury, which was confirmed by tubular dilation, albuminuria, increased Kim-1 and Ki67 mRNA expression, decreased megalin and Tamm–Horsfall protein (THP) expression. Finally, the treatment induced increases in CD68 protein staining, MCP-1, IL-1β, NFkappaB, and α-SMA mRNA expression, which are consistent with proinflammatory and profibrotic signaling, respectively. In conclusion, our findings provide relevant information regarding crystalline-induced AKI, showing strong tubulointerstitial and glomerular injury with a possible loss of podocyte viability.
Highlights
Oxalate is an end product of hepatic metabolism of glyoxylate, amino acids and carbohydrates (Gambardella and Richardson, 1977; Poore et al, 1997; Knight et al, 2011)
To confirm the establishment of the experimental model of NaOx-induced acute crystalline nephropathy, hematoxylin and eosin staining was performed and the staining revealed medullary casts and calcium oxalate (CaOx) crystals, which were confirmed by urinary sediment analysis (Figure 1A)
NaOx treatment induced a significant increase in glomerular desmin immunostaining (Figures 2A,B), decreased the WT1 immunofluorescence signal (Figures 2C,D) and Tamm–Horsfall protein (THP) protein expression and distribution in both cortical and increased nephrin mRNA expression (Figure 2E) in comparison medullary regions of the kidney in comparison to those observed to the control group
Summary
Oxalate is an end product of hepatic metabolism of glyoxylate, amino acids and carbohydrates (Gambardella and Richardson, 1977; Poore et al, 1997; Knight et al, 2011). In. Frontiers in Physiology | www.frontiersin.org de Araújo et al. Sodium Oxalate – Induced AKI addition, transcellular transport of oxalate is mediated by SLC26 anion exchangers expressed on both apical and basolateral membranes of intestinal epithelial cells (Efe et al, 2019; Knauf et al, 2019). Oxalate is primarily excreted by the kidneys via glomerular filtration and tubular secretion, the last one being mediated by the SLC26A anion exchanger expressed in the basolateral membrane (Robijn et al, 2011) and the Cl−/oxalate exchanger SLC26A6 expressed mainly in the brush-border membrane of proximal tubule cells (Bergsland et al, 2011; Knauf et al, 2019) and in the apical membrane of distal nephron cells (Kujala et al, 2005)
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