Targeting NaPi-IIb for Hyperphosphatemia in Chronic Kidney Disease Patients - The Dead End?

Apetrii, Mugurel; Covic, Adrian

doi:10.1016/j.ekir.2021.01.017

Cited by 1 publication

(1 citation statement)

References 11 publications

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“…Thus, NaPi-2b has been a major focus of drug targeting for reducing intestinal phosphorus absorption to treat hyperphosphatemia in patients with CKD. This year, results from a human phase 1b trial of a NaPi-2b inhibitor, DS-2330b – alone and in combination with sevelamer, were reported [18 ▪▪ ] with an accompanying commentary [19]. Despite preclinical rat studies showing effectiveness of the drug to reduce phosphorus absorption, the 14-day human trial did not show efficacy in reducing serum phosphate.…”

Section: Inhibition Of Transcellular Versus Paracellular Absorptionmentioning

confidence: 99%

Intestinal phosphorus absorption: recent findings in translational and clinical research

Gallant

Vorland

2021

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of reviewThe purpose of this review is to discuss recent findings in intestinal phosphorus absorption pathways, particularly the contributions of paracellular versus transcellular absorption, and the differential findings from studies using in vitro versus in vivo techniques of assessing phosphorus absorption in experimental animal studies.Recent findingsExperimental animal studies show that in vivo effects of low phosphorus diets, 1,25D, and chronic kidney disease on intestinal phosphorus absorption efficiency contradict effects previously established ex vivo/in vitro. Recent in vivo studies also suggest that the paracellular pathway accounts for the majority of phosphorus absorption in animals across very low to high luminal phosphate concentrations. The data from experimental animal studies correspond to recent human studies showing the effectiveness of targeted inhibition of paracellular phosphate absorption. Additionally, recent human studies have demonstrated that NaPi-2b inhibition alone does not appear to be effective in lowering serum phosphate levels in patients with chronic kidney disease. Pursuit of other transcellular phosphate transporter inhibitors may still hold promise.SummaryIn vivo animal and human studies have added to our understanding of intestinal phosphorus absorption pathways, regulation, and mechanisms. This is beneficial for developing effective new strategies for phosphate management in patients with chronic kidney disease.

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Section: Inhibition Of Transcellular Versus Paracellular Absorptionmentioning

confidence: 99%

Intestinal phosphorus absorption: recent findings in translational and clinical research

Gallant

Vorland

2021

Current Opinion in Nephrology &Amp; Hypertension

View full text Add to dashboard Cite

show abstract

Targeting NaPi-IIb for Hyperphosphatemia in Chronic Kidney Disease Patients - The Dead End?

Cited by 1 publication

References 11 publications

Intestinal phosphorus absorption: recent findings in translational and clinical research

Intestinal phosphorus absorption: recent findings in translational and clinical research

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