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Abstract: FR-PO507

Valsartan Mitigated CKD-MBD in Uremic Rats by Activation Klotho

Session Information

Category: Bone and Mineral Metabolism

  • 401 Bone and Mineral Metabolism: Basic

Author

  • Cheng, Ao, The Fist Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
Background

Valsartan as the most commonly one of ARB drugs, can effectively lower blood pressure and remit the progression of chronic kidney disease. In addition, we also observed that the ARB drugs could ameliorate the calcium and phosphorus metabolism in patients. The main purpose of this experiment is to explore whether valsartan could mitigate calcium and phosphorus metabolism and secondary hyperparathyroidism and seek the underlying signal pathway in uremic rats.

Methods

Animal Experiment: The rats were divided into three groups: sham group, 5/6 nephrectomy group, 5/6 nephrectomy + calcitriol group. 1) Through serum biochemical tests, to detect the levels of BUN, Creatine, Ca and P in various groups and determine expression of Klotho, TGFβ1, iPHT in serum. 2) By HE, Masson staining of renal tussues, Observation of fibrosis and collagen deposition in parathyroid tissue and renal tissue. 3) Detection expression of Klotho, TGFβ1, iPHT in parathyroid tussue by Immunohistochemical staining. 4) Detection expression of AT1, Klotho, TGFβ1, iPHT, E-cadherin and α-SMA in renal tussue by Immunohistochemical staining. 5) Using PCR and Western-Bloting detect expression of Klotho, TGFβ1, E-cadherin and α-SMA in renal tussues.

Results

(1) Valsartan could effectively reduce the elevated creatinine, BUN, improve the calcium and phosphorus metabolism and lessen iPTH in the 5/6 nephrectomy rats; (2) Valsartan can distinctly reduce parathyroid hyperplasia and iPTH expression, increased Klotho expression in parathyroid tissue; (3) Valsartan might ameliorate kidney injury and fibrosis by light microscopy; (4) In renal tissue, Valsartan may induce Klotho and E-cadherin expression and reduce iPTH, TGFβ1 and α-SMA expression.

Conclusion

Valsartan could suspress parathyroid hyperplasia and ameliorate kidney injury and fibrosis in uremic rats. Valsartan might delay the progression CKD-MBD in ESRD by increasing the expression of Klotho, reducing iPHT, improving calcium and phosphorus metabolism.

Funding

  • Government Support - Non-U.S.