Phosphate and Cardiovascular Disease beyond Chronic Kidney Disease and Vascular Calcification.

Sinee Disthabanchong

doi:10.1155/2018/3162806

Abstract

Phosphate is essential for life but its accumulation can be detrimental. In end-stage renal disease, widespread vascular calcification occurs as a result of chronic phosphate load. The accumulation of phosphate is likely to occur long before the rise in serum phosphate above the normal range since several observational studies in both general population and early-stage CKD patients have identified the relationship between high-normal serum phosphate and adverse cardiovascular outcomes. Consumption of food high in phosphate increases both fasting and postprandial serum phosphate and habitual intake of high phosphate diet is associated with aging, cardiac hypertrophy, endothelial dysfunction, and subclinical atherosclerosis. The decline in renal function and dietary phosphate load can increase circulating fibroblast growth factor-23 (FGF-23) which may have a direct impact on cardiomyocytes. Increased FGF-23 levels in both CKD and general populations are associated with left ventricular hypertrophy, congestive heart failure, atrial fibrillation, and mortality. Increased extracellular phosphate directly affects endothelial cells causing cell apoptosis and vascular smooth muscle cells (VSMCs) causing transformation to osteogenic phenotype. Excess of calcium and phosphate in the circulation can promote the formation of protein-mineral complex called calciprotein particles (CPPs). In CKD, these CPPs contain less calcification inhibitors, induce inflammation, and promote VSMC calcification.

Highlights

The discovery of phosphorus occurred by accident in 1669 when a German alchemist named Hennig Brand boiled down 60 buckets of urine in search of the “philosopher’s stone,” a compound that would turn ordinary metals into gold
In early stages of chronic kidney disease (CKD), serum phosphate is normally maintained within the normal range owing to the compensatory increase in fibroblast growth factor-23 (FGF-23) and parathyroid hormone up until the estimated glomerular filtration rate reaching 30 mL/min/1.73 m2
In a large cohort of healthy subjects with no known cardiovascular disease (CVD), dietary phosphate intake >1 gram/day was significantly associated with greater left ventricular mass after adjustment for confounders

Summary

Introduction

The discovery of phosphorus occurred by accident in 1669 when a German alchemist named Hennig Brand boiled down 60 buckets of urine in search of the “philosopher’s stone,” a compound that would turn ordinary metals into gold. The accumulation of phosphate can produce deleterious effects Such example can be seen in end-stage renal disease patients when widespread vascular and soft tissue calcifications occur as a result of chronic phosphate accumulation. In early stages of chronic kidney disease (CKD), serum phosphate is normally maintained within the normal range owing to the compensatory increase in fibroblast growth factor-23 (FGF-23) and parathyroid hormone up until the estimated glomerular filtration rate (eGFR) reaching 30 mL/min/1.73 m2. Beyond this point hyperphosphatemia begins to develop [2, 3] (Figure 1).

Serum Phosphate and Outcomes

Dietary Phosphate

Fibroblast Growth Factor-23

Findings

Extracellular Phosphate and Cytotoxicity