Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney Disease

2021 ◽  
Vol 32 (8) ◽  
pp. 1830-1832
Author(s):  
Kittrawee Kritmetapak ◽  
Rajiv Kumar
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Phosphate Absorption ◽  
Intestinal Phosphate Absorption

scholarly journals Small Intestinal Phosphate Absorption: Novel Therapeutic Implications

2021 ◽  
pp. 1-9
Author(s):  
Jerry Yee ◽  
David Rosenbaum ◽  
Jeffrey W. Jacobs ◽  
Stuart M. Sprague
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Paracellular Pathway ◽  
Phosphate Binders ◽  
Phosphate Absorption ◽  
Therapeutic Implications ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Dietary Phosphate ◽  
Intestinal Phosphate Absorption

<b><i>Background:</i></b> Chronic kidney disease (CKD) affects approximately 15% of adults in the USA. As CKD progresses, urinary phosphate excretion decreases and results in phosphate retention and, eventually, hyperphosphatemia. As hyperphosphatemia is associated with numerous adverse outcomes, including increased cardiovascular mortality, reduction in phosphorus concentrations is a guideline-recommended, established clinical practice. Dietary phosphate restriction, dialysis, and phosphate binders are currently the only options for phosphate management. However, many patients with hyperphosphatemia have phosphorus concentrations &#x3e;5.5 mg/dL, despite treatment. <b><i>Summary:</i></b> This review pre­sents recent advances in the understanding of intestinal phosphate absorption and therapeutic implications. Dietary phosphate is absorbed in the intestine through two distinct pathways, paracellular absorption and transcellular transport. Recent evidence indicates that the paracellular route accounts for 65–80% of total phosphate absorbed. Thus, the paracellular pathway is the dominant mechanism of phosphate absorption. Tenapanor is a first-in-class, non-phosphate binder that inhibits the sodium-hydrogen exchanger 3 or solute carrier family 9 member 3 (SLC9A3) encoded by the SLC9A3 gene, and blocks paracellular phosphate absorption. <b><i>Key Messages:</i></b> Targeted inhibition of sodium-hydrogen exchanger 3 effectively reduces paracellular permeability of phosphate. Novel therapies that target the paracellular pathway may improve phosphate control in chronic kidney disease.

scholarly journals Intestinal phosphate absorption: The paracellular pathway predominates?

2019 ◽  
Vol 244 (8) ◽  
pp. 646-654 ◽  
Author(s):  
Matthew Saurette ◽  
R Todd Alexander
Keyword(s):  
Kidney Disease ◽  
Animal Studies ◽  
Western Diet ◽  
Phosphate Absorption ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Gradient Based ◽  
Intestinal Phosphate Absorption ◽  
Stage Renal Disease ◽  
End Stage

Hyperphosphatemia is nearly universal in patients with advanced chronic kidney disease and end stage renal disease. Given the considerable negative sequelae associated with hyperphosphatemia, i.e. increased cardiovascular disease, hastening of renal failure and death, reducing serum phosphate is a goal of therapy. In the absence of sufficient renal function, intestinal phosphate absorption is the remaining target to reduce plasma phosphate levels. Much work has been done with respect to understanding transcellular phosphate absorption. Both animal studies using inducible or intestinal NaPi-2b knockout mice and specific NaPi-2b inhibitors revealed this transporter as the primary mechanism mediating transcellular phosphate absorption in the intestine. However, this has not translated into effective phosphate lowering therapies in patients with kidney disease. More recently, it was observed that inhibition of the epithelial sodium hydrogen exchanger, sodium–hydrogen exchanger isoform 3 (NHE3), or its genetic deletion, decreases intestinal phosphate absorption. The mechanism mediating this effect is through increased transepithelial resistance and reduced paracellular phosphate permeability. Thus, NHE3 inhibition reduces paracellular phosphate permeability in the intestine. The transepithelial potential difference across intestinal epithelium is lumen negative and phosphate commonly exists as a divalent anion. Further, consumption of the typical Western diet provides a large lumen to blood phosphate concentration gradient. Based on these observations we argue herein that the paracellular phosphate absorption route is the predominant pathway mediating intestinal phosphate absorption in humans. Impact statement This review summarizes the work on transcellular intestinal phosphate absorption, arguing why this pathway is not the predominant pathway in humans consuming a “Western” diet. We then highlight the recent evidence which is strongly consistent with paracellular intestinal phosphate absorption mediating the bulk of intestinal phosphate absorption in humans.

scholarly journals Intestinal Phosphorus Absorption in Chronic Kidney Disease

Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1364 ◽  
Author(s):  
Elizabeth Stremke ◽  
Kathleen Hill Gallant
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Hormonal Changes ◽  
Phosphorus Excretion ◽  
Phosphorus Absorption ◽  
Mineral Bone Disorder ◽  
Bone Disorder ◽  
Intestinal Phosphate Absorption ◽  
Homeostatic Response

Chronic kidney disease (CKD) affects approximately 10% of adults worldwide. Dysregulation of phosphorus homeostasis which occurs in CKD leads to development of CKD-Mineral Bone Disorder (CKD-MBD) and contributes to increased morbidity and mortality in these patients. Phosphorus is regulated by multiple hormones (parathyroid hormone (PTH), 1,25-dihyxdroxyvitamin D (1,25D), and fibroblast growth factor 23 (FGF23)) and tissues (kidney, intestine, parathyroid glands, and bone) to maintain homeostasis. In health, the kidneys are the major site of regulation for phosphorus homeostasis. However, as kidney function declines, the ability of the kidneys to adequately excrete phosphorus is reduced. The hormonal changes that occur with CKD would suggest that the intestine should compensate for impaired renal phosphorus excretion by reducing fractional intestinal phosphorus absorption. However, limited studies in CKD animal models and patients with CKD suggest that there may be a break in this homeostatic response where the intestine fails to compensate. As many existing therapies for phosphate management in CKD are aimed at reducing absolute intestinal phosphorus absorption, better understanding of the factors that influence fractional and absolute absorption, the mechanism by which intestinal phosphate absorption occurs, and how CKD modifies these is a much-needed area of study.

No effect of vitamin D supplementation on metabolic parameters but on lipids in patients with type 2 diabetes and chronic kidney disease

2020 ◽  
pp. 1-10
Author(s):  
Jiwoon Kim ◽  
Ji Sun Nam ◽  
Heejung Kim ◽  
Hye Sun Lee ◽  
Jung Eun Lee
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Vitamin D Supplementation ◽  
Lipid Profiles ◽  
Metabolic Parameters ◽  
Injection Group ◽  
Different Doses

Abstract. Background/Aims: Trials on the effects of cholecalciferol supplementation in type 2 diabetes with chronic kidney disease patients were underexplored. Therefore, the aim of this study was to investigate the effects of two different doses of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentrations and metabolic parameters in vitamin D-deficient Korean diabetes patients with chronic kidney disease. Methods: 92 patients completed this study: the placebo group (A, n = 33), the oral cholecalciferol 1,000 IU/day group (B, n = 34), or the single 200,000 IU injection group (C, n = 25, equivalent to 2,000 IU/day). 52% of the patients had less than 60 mL/min/1.73m2 of glomerular filtration rates. Laboratory test and pulse wave velocity were performed before and after supplementation. Results: After 12 weeks, serum 25(OH)D concentrations of the patients who received vitamin D supplementation were significantly increased (A, -2.4 ± 1.2 ng/mL vs. B, 10.7 ± 1.2 ng/mL vs. C, 14.6 ± 1.7 ng/mL; p < 0.001). In addition, the lipid profiles in the vitamin D injection group (C) showed a significant decrease in triglyceride and a rise in HDL cholesterol. However, the other parameters showed no differences. Conclusions: Our data indicated that two different doses and routes of vitamin D administration significantly and safely increased serum 25(OH)D concentrations in vitamin D-deficient diabetes patients with comorbid chronic kidney disease. In the group that received the higher vitamin D dose, the lipid profiles showed significant improvement, but there were no beneficial effects on other metabolic parameters.

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