Calcium and phosphorusHyperphosphatemia and vascular calcification in end-stage renal disease
Section snippets
Inorganic phosphate levels as an important regulator of vascular calcification
The molecular mechanisms regulating vascular calcification remain obscure. A clue to this process, however, is suggested by several observations linking serum phosphate levels with a tendency toward vascular calcification. First, a high serum phosphate level is highly correlated with the extent of vascular calcification and vascular disease.15, 16 One of the most common causes of hyperphosphatemia is chronic renal failure and subsequent kidney dialysis, in which serum inorganic phosphate levels
Inorganic phosphate levels regulate vascular smooth muscle cell calcification
We hypothesized that vascular smooth muscle cells (HSMC) might respond to elevated extracellular Pi levels by increasing promineralizing molecules, thereby leading to vascular calcification. The role of inorganic phosphate in vascular HSMC mineralization was investigated using an in vitro model system that was shown to mimic many of the features seen in human metastatic vascular calcification in vivo. We found that HSMC cultured in media containing normal serum phosphate levels do not
Evidence for a sodium-dependent phosphate cotransporter system in HSMC
How might HSMC sense elevated phosphate levels? To determine the mechanism by which HSMC sense elevated Pi levels, we examined phosphate uptake in the HSMC using radiolabeled Pi. HSMC took up Pi in a sodium-dependent and Pi gradient-dependent manner. These properties are consistent with the presence of a sodium-dependent phosphate cotransporter (NPC). Three types of NPCs have been identified to date and are grouped according to homology. Type I and type II NPCs are predominantly restricted to
HSMC culture mineralization is dependent on NPC function
To determine whether NPC function was important in HSMC culture calcification, we used the NPC inhibitor phosphonoformic acid (PFA). In the presence of PFA, HSMC Pi uptake was almost completely abolished. Inhibition of transport was dose-dependent, and half-maximal inhibition occurred between 0.1 and 0.5 mmol/L PFA. Consistent with a role in culture mineralization, PFA completely inhibited HSMC calcification. PFA effects were dose-dependent and half-maximal between 0.1 and 0.5 mmol/L PFA.
How
Increased phosphate level is associated with vascular calcification in dialysis patients
Vascular calcification, which significantly increases cardiovascular and other causes of mortality,28 is highly prevalent in dialysis patients. Factors affecting vascular calcification in dialysis patients include advanced age, derangement of calcium-phosphate metabolism,29 and diabetes.30 We examined 332 nondiabetic patients (192 male and 140 female, 59 ± 13 years). Hand roentgenography was performed, and visible vascular calcification of the hand arteries was evaluated. There were 45
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2018, Encyclopedia of Endocrine DiseasesRelationship between serum osteoprotegerin and vascular calcifications in hemodialysis patients
2017, Egyptian Heart JournalCitation Excerpt :Also, Nigel et al.2 reported that the presence and severity of AAC were related to age, duration of dialysis and the presence of cardiovascular disease, but there was no significant relationship between AACS and serum markers of mineral metabolism (phosphate, calcium, PTH, 25-hydroxy vitamin D), lipids, C-reactive protein or the presence of diabetes. Moreover, Nishizawa et al.49 concluded that the significant factors affecting vascular calcification were advanced age, longer duration of hemodialysis, increased phosphate concentrations and lower predialysis diastolic pressure. In the current study, CACS directly correlated with age, duration of hemodialysis, phosphorus, calcium, PTH, alkaline phosphatase and CRP, cholesterol, triglycerides, LDL, and inversely with HDL.
Complete resolution of calciphylaxis after kidney transplantation
2013, American Journal of Kidney DiseasesCitation Excerpt :Many theories emphasize the effect of hyperphosphatemia, which leads to soft-tissue mineralization of vascular smooth muscle. It has yet to be proved whether this effect, which has been shown in large vessels,7-9 also occurs in small arterioles. In the case of a well-functioning transplant, the patient's tubular function is restored and parathyroid hormone concentration decreases, which causes serum phosphate concentrations to normalize within months.10-12
Serum phosphate and hip bone mineral density as additional factors for high vascular calcification scores in a community-dwelling: The São Paulo Ageing & Health Study (SPAH)
2013, BoneCitation Excerpt :Interestingly, we observed an association of high AACS and serum phosphate, even within normal range. It has been hypothesized that serum phosphate is an important additional regulator of vascular calcification, since high serum phosphate in uremic patients is a well-known risk factor for vascular calcification [16]. The phosphate increased in these patients promotes mineralization of smooth muscle cells (SMC), in vivo and in vitro, leading to vascular calcification [35].
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