Emerging treatments and current strategies for mineral, vascular, and bone disorders in chronic kidney disease

Table 1 Phosphate management in advanced chronic kidney disease and end-stage kidney disease

Medication	Mechanism of action	Comments	Effect on GI system	Effect on cardiovascular system	Effect on bone	Ref.
Metal-based phosphate binders
Aluminum hydroxide	Formation of insoluble complexes with phosphate in GI tract prevents absorption of dietary phosphate	Use not recommended	Constipation, delayed gastric emptying	Anemia, accelerated dementia	Accumulation in the bone and bone pain	Slatopolsky et al[30], Drüeke[34]
Calcium carbonate, calcium acetate		Inexpensive. Calcium is absorbed systemically	Neutralizes gastric acid, increases GI motility	Hypercalcemia. Accelerated vascular calcifications, increased mortality with long-term use	No increase in fractures	Block et al[31], Di Iorio et al[32], Di Iorio et al[33]
Lanthanum carbonate		Chewable	Good GI tolerance	No improvement in mortality	No increase in bone fractures	Hutchison et al[35], Toussaint et al[36]
Ferric citrate, sucroferric oxyhydroxide		Lower pill burden. Decreased the need for erythropoiesis stimulating agents	Diarrhea, constipation, nausea, abdominal pain, and discolored stool	Additional iron delivery may help with management of heart failure but no high-quality data	No high-quality data	Pennoyer et al[37], Block et al[38], Vervloet et al[39]
Resin-based phosphate binders
Sevelamer carbonate, sevelamer hydrochloride	Formation of insoluble complexes with dietary phosphate	High pill burden, large size of tablets	Constipation, nausea	Decreased vascular calcifications compared to Ca-based binders	No increase in fractures	Di Iorio et al[32], Di Iorio et al[33]

GI: Gastrointestinal.

Table 2 Other and novel therapies for mineral bone disorder in advanced chronic kidney disease and end-stage kidney disease

Other therapies	Mechanism of action	Comments	Effect on GI system	Effect on cardiovascular system	Effect on bone	Ref.
Magnesium hydroxide	Pleiotropic effects on endothelial function and inflammation	Low pill burden. Does not need to be timed with meals	Loose stool, diarrhea	No change in coronary artery calcifications	No high-quality data	Bressendorff et al[65], Zhan et al[66]
Cinacalcet	Enhances sensitivity of calcium sensing receptor in parathyroid glands	Relatively low pill burden. Can be administered every other day with hemodialysis	Nausea, emesis, diarrhea	Reduction in cardiovascular mortality and all-cause mortality	Hypocalcemia. Reduction in bone fractures in patients with end-stage kidney disease over age 65	Moe et al[17], Chertow et al[67]
Novel therapies
Tenapanor	Inhibition of sodium/hydrogen exchanger isoform 3 transporter in GI tract	Low pill burden (one tablet twice daily). Does not need to be timed with meals	Osmotic diarrhea	No high-quality data	No high-quality data	Herekar et al[44], Block et al[45]
SNF472	Selective inhibition of formation and growth of hydroxyapatite crystals	Requires intravenous administration. Can be given after hemodialysis	Mild nausea, similar rate to placebo	Decrease in coronary artery calcifications	Slight reduction in bone density	Raggi et al[68], Bushinsky et al[69]

GI: Gastrointestinal.