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Small intestine resection increases oxalate and citrate transporter expression and calcium oxalate crystal formation in rat hyperoxaluric kidneys.
- Source :
-
Clinical science (London, England : 1979) [Clin Sci (Lond)] 2020 Oct 16; Vol. 134 (19), pp. 2565-2580. - Publication Year :
- 2020
-
Abstract
- Short bowel (SB) increases the risk of kidney stones. However, the underlying mechanism is unclear. Here, we examined how SB affected renal oxalate and citrate handlings for in vivo hyperoxaluric rats and in vitro tubular cells. SB was induced by small intestine resection in male Wistar rats. Sham-operated controls had no resection. After 7 days of recovery, the rats were divided into control, SB (both fed with distilled water), ethylene glycol (EG), and SB+EG (both fed with 0.75% EG for hyperoxaluric induction) groups for 28 days. We collected the plasma, 24 h of urine, kidney, and intestine tissues for analysis. Hypocitraturia was found and persisted up to 28 days for the SB group. Hypocalcemia and high plasma parathyroid hormone (PTH) levels were found in the 28-day SB rats. SB aggravated EG-mediated oxalate nephropathy by fostering hyperoxaluria and hypocitraturia, and increasing the degree of supersaturation and calcium oxalate (CaOx) crystal deposition. These effects were associated with renal up-regulations of the oxalate transporter solute carrier family 26 (Slc26)a6 and citrate transporter sodium-dependent dicarboxylate cotransporter-1 (NaDC-1) but not Slc26a2. The effects of PTH on the SB kidneys were then examined in NRK-52E tubular cells. Recombinant PTH attenuated oxalate-mediated cell injury and up-regulated NaDC-1 via protein kinase A (PKA) activation. PTH, however, showed no additive effects on oxalate-induced Slc26a6 and NaDC-1 up-regulation. Together, these results demonstrated that renal NaDC-1 upregulation-induced hypocitraturia weakened the defense against Slc26a6-mediated hyperoxaluria in SB kidneys for excess CaOx crystal formation. Increased tubular NaDC-1 expression caused by SB relied on PTH.<br /> (© 2020 The Author(s).)
- Subjects :
- Animals
Calcium blood
Calcium Oxalate blood
Crystallization
Cyclic AMP-Dependent Protein Kinases metabolism
Dicarboxylic Acid Transporters metabolism
Hyperoxaluria urine
Kidney metabolism
Kidney pathology
Male
Models, Biological
Parathyroid Hormone blood
Rats, Wistar
Signal Transduction
Up-Regulation
Calcium Oxalate metabolism
Carrier Proteins metabolism
Hyperoxaluria metabolism
Intestine, Small surgery
Oxalates metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1470-8736
- Volume :
- 134
- Issue :
- 19
- Database :
- MEDLINE
- Journal :
- Clinical science (London, England : 1979)
- Publication Type :
- Academic Journal
- Accession number :
- 33006369
- Full Text :
- https://doi.org/10.1042/CS20200973