Coming out of the PiTs—novel strategies for controlling intestinal phosphate absorption in patients with CKD

Wagner, Carsten A.

doi:10.1016/j.kint.2020.04.010

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…Inhibition of active Pi absorption in the intestine by the NaPi-IIb transporter has produced promising results in animal studies but has completely failed in phase 1 and 2 studies. A novel pan-inhibitor of intestinal Pi transporters reduces intestinal phosphate absorption in rats; human studies are awaited [ 111 ]. Tenapanor is a non-absorbable sodium–hydrogen exchanger 3 inhibitor that indirectly reduces intestinal paracellular Pi absorption.…”

Section: Therapies Targeting Phosphate Metabolismmentioning

confidence: 99%

The basics of phosphate metabolism

Wagner

2023

Nephrology Dialysis Transplantation

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Phosphorus is an essential mineral that is, in the form of inorganic phosphate (Pi), required for building cell membranes, DNA and RNA molecules, energy metabolism, signal transduction and pH buffering. In bone, Pi is essential for bone stability in the form of apatite. Intestinal absorption of dietary Pi depends on its bioavailability and has two distinct modes of active transcellular and passive paracellular absorption. Active transport is transporter mediated and partly regulated, while passive absorption depends mostly on bioavailability. Renal excretion controls systemic Pi levels, depends on transporters in the proximal tubule and is highly regulated. Deposition and release of Pi into and from soft tissues and bone has to be tightly controlled. The endocrine network coordinating intestinal absorption, renal excretion and bone turnover integrates dietary intake and metabolic requirements with renal excretion and is critical for bone stability and cardiovascular health during states of hypophosphataemia or hyperphosphataemia as evident from inborn or acquired diseases. This review provides an integrated overview of the biology of phosphate and Pi in mammals.

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Section: Therapies Targeting Phosphate Metabolismmentioning

confidence: 99%

The basics of phosphate metabolism

Wagner

2023

Nephrology Dialysis Transplantation

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“…Recently, a novel pan-inhibitor of sodium-dependent phosphate transporters, EOS789, has been shown to reduce fecal phosphorus excretion and urinary phosphorus excretion in normal rats in a dose-dependent manner, indicating effectiveness in reducing intestinal phosphorus absorption on a relatively high phosphorus diet of 0.81%P [24 ▪▪ ,25]. Significant reductions in serum phosphate, PTH, and FGF23 were also observed with higher EOS789 dosing.…”

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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“…With the very powerful analytical tools now available, the complexity, speed 2 and amazing co-ordination of the processes involved have become increasingly apparent [11,12,23,24]. Already, findings have shown new avenues for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders [12,19,23,[25][26][27][28][29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%

The Intricacies of Renal Phosphate Reabsorption—An Overview

Walker

2024

Preprint

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To maintain an optimal body content of phosphorus throughout postnatal life, variable phosphate absorption from food must be finely matched with urinary excretion. This amazing feat is accomplished through synchronised phosphate transport by myriads of ciliated cells lining the renal proximal tubules. These respond in real time to changes in the phosphate and composition of the renal filtrate, and to hormonal instructions. How they do this has stimulated decades of research. New analytical techniques, coupled with incredible advances in computer technology, have opened new avenues for investigation at a sub-cellular level. There has been a surge of research into different aspects of the process. These have verified long held beliefs and are also dramatically extending our vision of the intense, integrated, intracellular activity which mediates phosphate absorption. Already, some have indicated new approaches for pharmacological intervention to regulate phosphate in common conditions, including chronic renal failure and osteoporosis, as well as rare inherited biochemical disorders. It is a rapidly evolving field. The aim here is to provide an overview of our current knowledge, to show where it is leading, and where there are uncertainties. Hopefully this will raise questions and stimulate new ideas for further research.

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Coming out of the PiTs—novel strategies for controlling intestinal phosphate absorption in patients with CKD

Cited by 6 publications

References 9 publications

The basics of phosphate metabolism

The basics of phosphate metabolism

Intestinal phosphorus absorption: recent findings in translational and clinical research

The Intricacies of Renal Phosphate Reabsorption—An Overview

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