Lanthanum carbonate 500mg chewable tablets

BACKGROUND: Phosphate binders are used to manage hyperphosphatemia in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and may influence fibroblast growth factor 23 (FGF-23), a biomarker associated with disease progression and mortality. However, the comparative effects of calcium-based phosphate binders (CPBs) and non-calcium-based phosphate binders (NCPBs) on FGF-23 levels remain unclear. We conducted a meta-analysis of randomized controlled trials to compare the effects of NCPBs and CPBs on FGF-23 levels in patients with CKD-MBD with hyperphosphatemia. METHODS: A systematic search of PubMed, EMBASE, and the Cochrane Library was performed for studies published up to August 2024. Only randomized controlled trials were eligible; non-randomized controlled trials, studies with overlapping patient populations, pediatric or animal studies, and trials without quantitative FGF-23 outcomes were excluded. Language restrictions were not imposed. Data were synthesized as standardized mean differences using a random-effects model, and the risk of bias was assessed using the Cochrane Risk of Bias 2 tool. RESULTS: Eleven randomized controlled trials involving 791 patients were included. Overall, NCPBs were associated with a greater reduction in FGF-23 levels compared with CPBs (standardized mean difference −0.56, 95% confidence interval −0.95 to −0.17, p = 0.005). Subgroup analyses suggested consistent trends across binder types (sevelamer and lanthanum), dialysis status, and treatment duration. However, the subgroup differences were not statistically significant, and heterogeneity remained substantial in several subgroups, indicating that these findings should be interpreted with caution. CONCLUSIONS: In CKD-MBD patients with hyperphosphatemia, NCPBs were associated with greater reductions in FGF-23 levels compared with CPBs. The subgroup results suggested possible trends by binder type, CKD category, and treatment duration. However, given the heterogeneity and lack of statistically significant subgroup differences, these findings should be considered hypothesis-generating. Further well-designed trials are needed to confirm these results and clarify the underlying mechanisms and clinical implications.

Abstract licence: CC BY-NC-ND

IntroductionPrimary hyperoxaluria (PH) is a devastating disease in children and adults. Recently, a substantial progress in the treatment of this deadly disease has been made that consists of the introduction of the RNA inhibitors, lumasiran and nedosiran, which deplete the substrate for oxalate synthesis.MethodsLanthanum carbonate (Lanth.Carb., La2[CO3]3) is a powerful phosphate binder having a strong affinity to oxalate. Its use as such in PH is not relevant because patients with normal renal function develop a severe phosphate depletion without a clear effect on oxalate balance. Considering that the absorption of phosphate is in the early gastrointestinal (GI) tract and mainly in the distal part of the GI tract for oxalate, we developed a targeted release capsule (trc) containing 500 mg Lant.Carb. released in the distal part of the GI tract as proven by radiological investigations of the radiopaque trcLanth.Carb.ResultsFour patients with PH and estimated glomerular filtration rate > 60 ml/min per 1.73 m2 were treated with trcLanth.Carb., which turned out to decrease the urinary oxalate concentrations clearly 2,45 mg/24 h per 1.73 m2 (considered as upper limit of normal), after 2.5 months of treatment in 3 patients and 18 months in 1 patient. Calciuria remained normal or decreased slightly. Phosphaturia and phosphatemia remained normal and stable in all 4 cases.ConclusiontrcLanth.Carb. is a promising repurposed, efficient, nontoxic, and cheap drug, lacking serious side effects in the treatment of any type of PH in whatever place in the world. A randomized controlled trial supporting this proof-of-concept is the next step.

Abstract licence: CC BY-NC-ND