Colestilan 3g granules sachets

BackgroundGuidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD.Study DesignNetwork meta-analysis.Setting & PopulationAdults with CKD.Selection Criteria for StudiesRandomized trials with allocation to phosphate binders.InterventionsSevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium.OutcomesThe primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification.Results77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium.LimitationsLimited testing of consistency; short follow-up.ConclusionsThere is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials. Guidelines preferentially recommend noncalcium phosphate binders in adults with chronic kidney disease (CKD). We compare and rank phosphate-binder strategies for CKD. Network meta-analysis. Adults with CKD. Randomized trials with allocation to phosphate binders. Sevelamer, lanthanum, iron, calcium, colestilan, bixalomer, nicotinic acid, and magnesium. The primary outcome was all-cause mortality. Additional outcomes were cardiovascular mortality, myocardial infarction, stroke, adverse events, serum phosphorus and calcium levels, and coronary artery calcification. 77 trials (12,562 participants) were included. Most (62 trials in 11,009 patients) studies were performed in a dialysis population. Trials were generally of short duration (median, 6 months) and had high risks of bias. All-cause mortality was ascertained in 20 studies during 86,744 patient-months of follow-up. There was no evidence that any drug class lowered mortality or cardiovascular events when compared to placebo. Compared to calcium, sevelamer reduced all-cause mortality (OR, 0.39; 95% CI, 0.21-0.74), whereas treatment effects of lanthanum, iron, and colestilan were not significant (ORs of 0.78 [95% CI, 0.16-3.72], 0.37 [95% CI, 0.09-1.60], and 0.55 [95% CI, 0.07-4.43], respectively). Lanthanum caused nausea, whereas sevelamer posed the highest risk for constipation and iron caused diarrhea. All phosphate binders lowered serum phosphorus levels to a greater extent than placebo, with iron ranked as the best treatment. Sevelamer and lanthanum posed substantially lower risks for hypercalcemia than calcium. Limited testing of consistency; short follow-up. There is currently no evidence that phosphate-binder treatment reduces mortality compared to placebo in adults with CKD. It is not clear whether the higher mortality with calcium versus sevelamer reflects whether there is net harm associated with calcium, net benefit with sevelamer, both, or neither. Iron-based binders show evidence of greater phosphate lowering that warrants further examination in randomized trials.

Abstract licence: CC BY-NC-ND

Objective: To evaluate the efficacy and safety of 12 phosphorus-lowering drugs for hyperphosphatemia in chronic kidney disease 3-5 stages. Study Design & Methods: Systematic review and network meta-analysis of randomized controlled trials (RCTs). We searched 3 databases from inception through September 2023 for RCTs evaluating 12 phosphorus-lowering drugs. We performed frequentist random-effects network meta-analyses and present mean differences and 95% CIs. Subgroup analyses were performed between the dialysis and nondialysis patients to assess robustness, source of heterogeneity, and risk of bias using the Cochrane risk of bias assessment tool. Results: We included 121 trials (18,376 participants) and compared 13 drugs or placebo. In terms of efficacy, except for sodium ferrous citrate, all drugs lowered the level of serum phosphorus compared with placebo. Sucroferric oxyhydroxide (PA21), nicotinic acid, and tenapanor were most likely to be ranked the best, second best, or third best. Calcium/magnesium carbonate, nicotinic acid, and colestilan posed lower risks for hypercalcemia than calcium-based phosphorus binders. All phosphorus-lowering drugs significantly affect serum intact parathyroid hormone levels compared with placebo. Colestilan, tenapanor, and PA21 posed a higher risk for gastrointestinal discomfort. In addition, iron-containing drugs showed positive effects on iron parameters. Limitations: Few high-quality RCTs; unclear allocation concealment and blinding; low evidence quality reduced reliability. Conclusions: PA21 has the best phosphorus-lowering effect in hyperphosphatemic adults with chronic kidney disease; considering efficacy and safety, calcium carbonate shows evidence of being the most appropriate drug with or without dialysis. Registration: Registered at PROSPERO (CRD42024500243).

Abstract licence: CC BY-NC-ND

Bile acid sequestrants (BASs) are non-systemic therapeutic agents used for the management of hypercholesterolemia. They are generally safe and not associated with serious systemic adverse effects. Usually, BASs are cationic polymeric gels that have the ability to bind bile salts in the small intestine and eliminate them by excretion of the non-absorbable polymer-bile salt complex. This review gives a general presentation of bile acids and the characteristics and mechanisms of action of BASs. The chemical structures and methods of synthesis are shown for commercial BASs of first- (cholestyramine, colextran, and colestipol) and second-generation (colesevelam and colestilan) and potential BASs. The latter are based on either synthetic polymers such as poly((meth)acrylates/acrylamides), poly(alkylamines), poly(allylamines) and vinyl benzyl amino polymers or biopolymers, such as cellulose, dextran, pullulan, methylan, and poly(cyclodextrins). A separate section is dedicated to molecular imprinting polymers (MIPs) because of their great selectivity and affinity for the template molecules used in the imprinting technique. Focus is given to the understanding of the relationships between the chemical structure of these cross-linked polymers and their potential to bind bile salts. The synthetic pathways used in obtaining BASs and their in vitro and in vivo hypolipidemic activities are also introduced.

Abstract licence: CC BY