Mechanism Of CaSR In The Formation Of Kidney Stone

Objective:Urinary calculi is a worldwide disease.In recent years, There is a increasing tendency on its incidence.Doctors have made significant progress on the diagnosis and treatment of urinary calculi. But its formation mechanism has not been maded clear. Generally speaking, the following four aspects are still the main mechanism of stone formation.1.Supersaturated urine of stone substances, including high calcium oxalate urinary hypercalciuria, high uric acid urine and so on.2.The decrease of Inhibition or the increase of promotion.3. The damage of renal tubular epithelial cell.4. The formation of Randalls plaques.Calcium sensitive receptors were found over the years which is one of macromolecular proteins related with urinary calcium metabolism. And it have a close relationship with the formation of kidney stones, especially calcium stones. In order to clarify calcium sensitive recepter’s role in the formation of kidney stones.We study the changes of CaSR activity on the effect of calcium oxalate stone formation.Methods:Adult male Sprague Dawley rats were given ethylene glycol and Ammonium chloride to induce urolithiasis.Meanwhile, the rats received Different doses of CaSR inhibitors(NPS-2390). the levels of serum urea, creatinine, P, Ca2+and Mg2+, PTH,24h urine volume, urine pH, Ca2+, Mg2+and oxalate were evaluated at the end of the experiment. Kidney sections were examined under a light microscope to study the calcium oxalate crystal deposition and pathological changes and the expression of CaSR to study the changes of CaSR activity on the effect of calcium oxalate stone formation.Results:The urolithiasis induced by ethylene glycol and Ammonium chloride not only caused significant increase in the levels of serum urea and creatinine, urine oxalate and Ca2+, but also lots of calcium oxalate crystal deposition in kidey. PTH secretion of CaSR inhibitor group increased and blood Ca2+urine Ca2+rised.Renal histopathologic examination showed significant increase in calcium oxalate crystals in the kidney tissue of the CaSR inhibitor group,and kidney tissue damage is obvious.Conclusions:In the kidney and parathyroid gland the low expression of CaSR can increase the formation of calcium oxalate crystal.