Kidney Week

Abstract: TH-PO1062

Alteration of Renal Claudins in Rats with Hypercalciuria

Session Information

• Mineral Disease: Ca/Mg/PO4
  November 02, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Mineral Disease

• 1201 Mineral Disease: Ca/Mg/PO4

Authors

• Kim, Gheun-Ho, Hanyang University College of Medicine, Seoul, Korea (the Republic of)

Gheun-Ho Kim,

• Oh, Il hwan, Hanyang University College of Medicine, Seoul, Korea (the Republic of)

Il hwan Oh,

Background

Ninety-eight to 99% of the filtered load of calcium is reabsorbed by the renal tubules. Whereas most of the calcium reabsorption passively occurs in the proximal tubule through tight junctions, the distal nephron has been known as the major site for regulation of calcium excretion. Claudins form the conductive and selective part of the tight junctions along the nephron and may be involved in regulatory events in the control of calcium transport. This study was undertaken to test if the renal expression of claudins are altered in the different settings of hypercalciuria.

Methods

Male Spraugue-Dawley rats were used for three different animal protocols: CaCO₃, NaCl, and NH₄Cl loading. The rats were randomly divided into control (n=6) and treated (n=6) group in each experiment, and a daily fixed amount of food flurry was given to each rat. The control diet contained 0.8% calcium and 0.3% NaCl, and the treated diet had additional CaCO₃ (6%), NaCl (7%), or NH₄Cl (7.2 mmol/220 g BW) for 7 days. Plasma and urine data were followed, and kidneys were harvested for immunoblotting and qPCR analysis at the end of our animal experiment.

Results

Hypercalciuria was successfully induced by CaCO₃, NaCl, and NH₄Cl loading, and fractional excretion of calcium was significantly increased by the loading of CaCO₃ (5.00 ± 0.92 vs. 0.27 ± 0.08%, P < 0.05), NaCl (2.07 ± 0.57 vs. 0.25 ± 0.27%, P < 0.05), and NH₄Cl (0.90 ± 0.36 vs. 0.27 ± 0.12%, P < 0.05). The abundance of claudin-2 protein was not significantly altered by CaCO₃ or NaCl loading, but both claudin-2 protein (85 ± 9 vs. 100 ± 11%, P < 0.05) and mRNA (49 ± 23 vs. 100 ± 17%, P < 0.05) expression were significantly decreased by NH₄Cl loading. In response to CaCO₃ loading, the protein abundance of claudin-4 (47 ± 17 vs. 100 ± 12 %, P<0.05) and occludin (59 ± 17 vs. 100 ± 25%, P<0.05) were decreased, suggestive of changes in distal nephron. Interestingly, claudin-7 protein was decreased by NaCl loading (29 ± 14 vs. 100 ± 34%, P<0.05).

Conclusion

We confirmed that hypercalciuria in metabolic acidosis is associated with claudin-2 down-regulation in the proximal tubule. However, hypercalciuria induced by high calcium or salt intake was not accompanied by claudin-2 dysregulation. Further studies are required to investigate the regulatory role of paracellular calcium transport in the distal nephron.