Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study

Ma, Zixing; Tang, Yu; Wu, Yan; Liu, Dandan; Zhang, Xiaofei; Miao, Xin; Xing, Haiyan

doi:10.1016/j.biopha.2018.12.107

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Lanthanum absorbed into the body is mainly excreted through the liver, and therefore, it is suitable for dialysis patients. In the preliminary research of the research group, it was found that nano-lanthanum hydroxide can satisfactorily reduce phosphorus and also has a protective effect on the kidneys (Ma et al, 2019). The present work aimed to explore the clinical efficacy of lanthanum hydroxide in treating vascular calcification induced by hyperphosphate in the context of chronic renal failure (CRF).…”

Section: Introductionmentioning

confidence: 97%

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

Zhao

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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ObjectiveThe 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.MethodsRats 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 (SM22α, Runx2, BMP-2, and TRAF6) and Western blot (SM22α, Runx2, BMP-2, TRAF6, and NF-κB) were performed.ResultsIn 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-κB signal transduction pathway. For the cultured VSMCs, lanthanum chloride (LaCl3) alleviated phosphate-mediated calcification and suppressed the activation of NF-κB as well as osteo-/chondrogenic signal transduction. Lanthanum hydroxide evidently downregulated NF-κB, BMP-2, Runx2, and TRAF6 expression.ConclusionLanthanum hydroxide protects against renal failure and reduces the phosphorus level in serum to postpone vascular calcification progression.

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Section: Introductionmentioning

confidence: 97%

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

Zhao

Wang

Liu

et al. 2021

Front. Cell Dev. Biol.

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“…Their water solubility is low, and they are difficult to pass through the intestinal wall into the blood, so they can be excreted through feces to reduce phosphorus. In previous research conducted by our group, we found that nano-LH can effectively reduce serum phosphorus levels and protect kidney function (Ma et al, 2019). We recently showed that LH can inhibit the occurrence and development of VC in chronic renal failure, but the mechanism of its effect is still unclear.…”

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confidence: 93%

Lanthanum hydroxide inhibits vascular calcification by regulating the HIF‐1 pathway

Wang

Zhao

Liu

et al. 2022

Cell Biology International

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The main reason for the high incidence of cardiovascular disease in chronic kidney disease (CKD) patients with vascular calcification (VC) is also the main cause of death in CKD patients. Lanthanum hydroxide (LH) has an inhibitory effect on VC in chronic renal failure; however, the mechanism of its inhibition is poorly defined. Here, we used network pharmacology analysis and found that hypoxia-inducible factor (HIF) is related to VC. In a CKD rat model induced by adenine combined with high phosphorus (1.2%), LH improved the survival rate and inhibited the occurrence and development of VC. In an in vitro study, we found that lanthanum chloride inhibited the occurrence of VC induced by high phosphorus and reduced the production of reactive oxygen species. This study thus revealed that LH can inhibit the occurrence and development of VC by inhibiting the activation of HIF-1.

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“…Lanthanum phosphate has low water solubility, does not pass easily through the intestinal wall, and can be excreted through the feces, thereby achieving the effect of alleviating renal failure in CKD rat models, decreasing serum phosphorus levels, and inhibiting vascular calcification, equivalent to the effects of lanthanum carbonate (LC). 15 , 16 ) LC has been used clinically and is regarded as safe, 17 ) so it is suggested that the safety of LH may also be good. Because of the long-term administration in our experiment, there is a very small amount of absorption of lanthanum ions.…”

Section: Introductionmentioning

confidence: 99%

Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease

Gao

Han

et al. 2022

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

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Previous studies showed that lanthanum hydroxide (LH) has a therapeutic effect on chronic kidney disease (CKD) and vascular calcification, which suggests that it might have clinical value. However, the target and mechanism of action of LH are unclear. Metabolomics of clinical samples can be used to predict the mechanism of drug action. In this study, metabolomic profiles in patients with end-stage renal disease (ESRD) were used to screen related signaling pathways, and we verified the influence of LH on the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway by western blotting and quantitative real-time RT-qPCR in vivo and in vitro . We found that ROS and SLC16A10 genes were activated in patients with ESRD. The SLC16A10 gene is associated with six significant metabolites (L-cysteine, L-cystine, L-isoleucine, L-arginine, L-aspartic acid, and L-phenylalanine) and the PI3K-AKT signaling pathway. The results showed that LH inhibits the ESRD process and its cardiovascular complications by inhibiting the ROS-PI3K-AKT-mTOR-HIF-1α signaling pathway. Collectively, LH may be a candidate phosphorus binder for the treatment of vascular calcification in ESRD.

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Nano-lanthanum hydroxide, a novel phosphate binder, for treating hyperphosphatemia: A preclinical study

Cited by 7 publications

References 6 publications

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

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

Lanthanum hydroxide inhibits vascular calcification by regulating the HIF‐1 pathway

Metabolomics of clinical samples reveal the treatment mechanism of lanthanum hydroxide on vascular calcification in chronic kidney disease

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