The Rising Risk of Chronic Kidney Disease (CKD) and How it is Dealt With: A Review of Current and Potential Phosphate Binders (PB)

: It is estimated that by 2040 Chronic Kidney Disease (CKD) will be the 5th main cause of global deaths. It has been suggested that hyperphosphatemia is among the main factors leading to the increased risk of death. This review focuses on potential and currently used phosphate binders (PB). Aluminum hydroxide is presently not recommended due to potential aluminum toxicity. Calcium‑containing phosphate binders (CCPB) can cause calcium overload, resulting in hypercalcemia and an increased risk of cardiovascular diseases. Magnesium and calcium complexes were suggested to be as effective as sevelamer in the reduction of serum phosphate, with the potential to slow down the process of calcification. However, limited studies have been conducted in this area. Although sevelamer seemed to have a positive influence on cardiovascular calcification and arterial stiffness, its influence on mortality was unclear. Sevelamer crystal accumulation in the gastrointestinal tract (GI) can cause gastrointestinal bleeding. Lanthanum carbonate seemed to lower all-cause mortality and reduce the chance of hypercalcemia, even though a deposit in the GI tract was observed. Colestilan, like sevelamer, lowered LDL cholesterol. Sucroferric oxyhydroxide had a lower pill burden than other PBs, and it seemed to reduce serum FGF-23. Ferric citrate improved parameters that are related to anemia but can cause iron overload. Bixalomer appeared to have fewer gastrointestinal side effects than sevelamer. Nano-lanthanum hydroxide and SBR759 may have an interesting future as PBs. In conclusion, the development of new PBs should also take into consideration their potential to function as protection modifiers.

Lanthanum Hydroxide Protects Kidney Through Gut-Metabolite-Kidney Axis in a Rat Model of CKD

Background: Recent evidence suggests alterations in the gut-kidney axis may drive chronic kidney disease (CKD). Results: In the present study, we observed that administration of adenine to rats induced CKD, gut microbial dysbiosis, kidney pathology, and amino acid metabolism. In this model of CKD hyperphosphatemia, lanthanum hydroxide improved kidney function in CKD rats by restoring gut microbial homeostasis, thereby increasing urine ammonium metabolism. These findings demonstrated that lanthanum hydroxide improves kidney function in a CKD model in mice by restoring homeostasis of the gut-metabolite-kidney axis, which alleviated an amino acid imbalance. Lanthanum hydroxide thus shows therapeutic potential for patients with CKD, through reshaping the composition of gut microbiota.Conclusions: Lanthanum hydroxide plays a kidney protective role through the gut-metabolite-kidney axis in a rat model of chronic kidney disease caused by adenine.

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

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.