Regulation of renal phosphate handling: inter-organ communication in health and disease

Tatsumi, Sawako; Miyagawa, Atsumi; Kaneko, Ichiro; Shiozaki, Yuji; Segawa, Hiroko; Miyamoto, Ken‐ichi

doi:10.1007/s00774-015-0705-z

Cited by 30 publications

(20 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These hormones act on the renal proximal tubules and down-regulate sodium-Pi co-transporter type IIa and IIc, important transporters that regulate Pi resorption in the renal tubules, thereby increasing renal Pi excretion and maintaining serum Pi level within normal range [31]. However, as CKD reaches advanced stages, kidneys can no longer filter as much Pi as dietary Pi intake, finally leading to overt hyperphosphatemia at CKD stages 4 and 5.…”

Section: Elevated Pi As a Major Inducer Of Vcmentioning

confidence: 99%

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Yamada

Giachelli

2017

Bone

238

196

View full text Add to dashboard Cite

Vascular calcification (VC) is highly prevalent in aging, diabetes mellitus, and chronic kidney disease (CKD). VC is a strong predictor of cardiovascular morbidity and mortality in the CKD population. Complex pathological mechanisms are involved in the development of VC, including osteochondrogenic differentiation and apoptosis of vascular smooth muscle cells, instability and release of extracellular vesicles loaded calcium and phosphate, and elastin degradation. Elevated serum phosphate is a late manifestation of CKD, and has been shown to accelerate mineral deposition in both the vessel wall and heart valves. α-Klotho and fibroblast growth factor 23 (FGF23) are emerging factors in CKD-mineral and bone disorder (CKD-MBD) and are thought to be involved in the pathogenesis of uremic VC. There are discordant reports regarding the biomedical effects of FGF23 on VC. In contrast, mounting evidence supports a well-supported protective role for α-Klotho on VC. Further studies are warranted to elucidate potential roles of FGF23 and α-Klotho in VC and to determine where and how they are synthesized in normal and disease conditions. A thorough systemic evaluation of the biomedical interplay of phosphate, FGF23, and α-Klotho may potentially lead to new therapeutic options for patients with CKD-MBD.

show abstract

Section: Elevated Pi As a Major Inducer Of Vcmentioning

confidence: 99%

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Yamada

Giachelli

2017

Bone

238

196

View full text Add to dashboard Cite

show abstract

“…The pathophysiology of postoperative hypophosphatemia is likely multifactorial. Phosphate levels are regulated by a network of various organs, including bone, parathyroid glands, small intestine, liver, and kidneys 8 . For years, it was believed that in patients undergoing hepatectomy, liver regeneration and subsequent increased hepatic uptake of phosphate were responsible for the phosphate depletion 9–11 .…”

Section: Introductionmentioning

confidence: 99%

Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase

Zheng

Glezerman

Sadot

et al. 2017

Journal of the American College of Surgeons

View full text Add to dashboard Cite

Background Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia. Study designs We prospectively enrolled 120 patients who underwent major hepatectomy (n=30), minor hepatectomy (n=30), pancreatectomy (n=30), and laparotomy without resection (control group, n=30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH) were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide (2-PY) and N-methyl-4-pyridone-3-carboxamide (4-PY). Results We found that significant hypophosphatemia occurred from postoperative day (POD) to POD2 in all 4 groups were preceded by hyperphosphaturia from preoperative day to POD1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD2 in all 3 resected groups but not in the control group. FGF-23 levels were significantly decreased postoperatively in all 4 groups while PTH levels did not change in any of the 4 groups. Urine levels of 2-PY and 4-PY significantly decreased in all 4 groups postoperatively. Conclusions This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant further investigation.

show abstract

“…This process takes place to a major extent along the proximal tubule and it can be regulated according to the body's requirements (for review see [3][4][5]). Members of two families of Na Thomas/Wagner/Biber/Hernando: Effects of Luminal Phosphate in OK Cells…”

Section: Introductionmentioning

confidence: 99%

Adaptation of Opossum Kidney Cells to Luminal Phosphate: Effects of Phosphonoformic Acid and Kinase Inhibitors

Thomas

Wagner

Biber

et al. 2016

Kidney Blood Press Res

View full text Add to dashboard Cite

Background/Aims: Renal reabsorption of inorganic phosphate (Pi) is mediated by SLC34 and SLC20 Na⁺/Pi-cotransporters the abundance of which is under hormonal control. Extracellular Pi itself also regulates the expression of cotransporters and the concentration of Pi-regulating hormones, though the signaling pathways are largely unknown. Here, we explored the mechanisms that allow renal proximal cells to adapt to changes in the concentration of Pi. Methods: opossum kidney (OK) cells, a model of proximal epithelia, were incubated with different concentrations of Pi in the absence/presence of phosphonoformic acid (PFA), a Pi-analogue and SLC34-inhibitor, and of inhibitors of kinases involved in hormonal control of Pi-homeostasis; cells cultured in normal media were treated with uncouplers of oxidative phosphorylation. Then, the intracellular concentration of ATP and/or the Pi-transport capacity of the cultures were analyzed. Results: luminal Pi regulates the Pi-transport and the intracellular ATP levels. Changes in ATP seem secondary to alterations in Pi-transport, rather than ATP acting as a signal. Adaptation of Pi-transport to high Pi was not mimicked by PFA. Transport adaptation was blocked by PFA but not by kinase inhibitors. Conclusions: in OK cells, adaptation of Pi-transport to luminal Pi does not depend on the same signaling pathways involved in hormonal regulation.

show abstract

Regulation of renal phosphate handling: inter-organ communication in health and disease

Cited by 30 publications

References 118 publications

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Vascular calcification in CKD-MBD: Roles for phosphate, FGF23, and Klotho

Hypophosphatemia after Hepatectomy or Pancreatectomy: Role of the Nicotinamide Phosphoribosyltransferase

Adaptation of Opossum Kidney Cells to Luminal Phosphate: Effects of Phosphonoformic Acid and Kinase Inhibitors

Contact Info

Product

Resources

About