The Pharmacological Effect and Mechanism of Lanthanum Hydroxide on Vascular Calcification Caused by Chronic Renal Failure Hyperphosphatemia

Objective The present work aimed to explore the efficacy of lanthanum hydroxide in managing the vascular calcification induced by hyperphosphate in chronic renal failure (CRF) as well as the underlying mechanism. Methods Rats were randomly allocated to five groups: normal diet control, CKD hyperphosphatemia model, CKD model treated with lanthanum hydroxide, CKD model receiving lanthanum carbonate treatment, together with CKD model receiving calcium carbonate treatment. The serum biochemical and kidney histopathological parameters were analyzed. The aortic vessels were subjected to Von Kossa staining, CT scan and proteomic analysis. In vitro, the calcium content and ALP activity were measured, and RT-PCR (SM22 alpha, Runx2, BMP-2, and TRAF6) and Western blot (SM22 alpha, Runx2, BMP-2, TRAF6, and NF-kappa B) were performed. Results In the lanthanum hydroxide group, serum biochemical and kidney histopathological parameters were significantly improved compared with the model group, indicating the efficacy of lanthanum hydroxide in postponing CRF progression and in protecting renal function. In addition, applying lanthanum hydroxide postponed hyperphosphatemia-mediated vascular calcification in CKD. Furthermore, lanthanum hydroxide was found to mitigate vascular calcification via the NF-kappa B signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-kappa B as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-kappa B, BMP-2, Runx2, and TRAF6 expression. Conclusion Lanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

Automated summary

Lanthanum hydroxide demonstrates significant therapeutic effects in managing chronic renal failure, delaying disease progression and protecting renal function. It also effectively postpones vascular calcification induced by hyperphosphatemia in CKD and mitigates calcification through the NF-kappa B signal transduction pathway.