An update on calcium metabolism alterations and cardiovascular risk in patients with chronic kidney disease: questions, myths and facts.

In 2006, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines introduced, for the first time, the definition and diagnostic and therapeutic criteria for a systemic complication of the mineral metabolism dysfunction, such as vascular calcification, caused by chronic renal insufficiency. Abdominal x-ray and echocardiography rather than the more complex CT scan is suggested to make the diagnosis. This condition is associated with high cardiovascular risk and consequent poor prognosis. An alteration in total body calcium (Ca) content is one of the key factors in the cardiovascular complications observed in uremic subjects. In the general population, the addition of Ca to the diet has been to shown to improve bone mineral density (BMD) compared to controls, but it does not appear to reduce the risk of bone fractures. In patients with CKD, there are certainly some theoretical justifications for administering calcium salts: vitamin D deficiency, which reduces the intestinal absorption of Ca; hypocalcemia, which increases the risk of hyperparathyroidism; and hyperphosphatemia, which justifies the use of Ca-based P binders. There is already a large body of evidence pointing against the use of Ca-based binding agents, when there is a positive Ca balance because of the development of vascular calcification.

Salivary glands: a new player in phosphorus metabolism.

In uremic patients, hyperphosphatemia is associated with cardiovascular calcification and increased cardiovascular mortality. Despite the use of phosphate binders and dietary phosphate limitation in addition to dialysis, only 50% of dialysis patients achieve recommended serum phosphate levels. The identification of other approaches for serum phosphorus reduction is therefore necessary. We have approached this issue by taking into account the relationships between serum phosphate, kidney function, and saliva. Saliva was chosen because the anatomy and/or physiology of acini, the secretive units of salivary glands, shares similarities with that of the renal tubules. Salivary fluid contains electrolytes including phosphate that, when related with the amount of salivary secretion per day, raises the interest in identifying another possible approach for phosphorus removal in uremic patients. This article reports studies from our laboratory in the last 3 to 4 years, which have demonstrated a hyperphosphoric salivary content in patients with chronic renal failure and those with end-stage renal disease under chronic dialysis that, in patients with chronic renal failure, linearly correlates with serum phosphate in patients with chronic renal failure and negatively with GFR. The ingestion of the saliva and later its absorption in the intestinal tract starts a vicious circle between salivary phosphate secretion and fasting phosphate absorption, thereby worsening hyperphosphatemia. Therefore, salivary phosphate binding could be a useful approach to serum phosphate level reduction in dialysis patients. The reduction of salivary phosphate with the salivary phosphate binder, chitosan-loaded chewing gum, chewed during fasting periods, as an add-on to phosphate binders could lead to a better control of hyperphosphatemia, as demonstrated in our study, which confirms the importance of this approach.

Phosphorus: the philosopher's stone discovered in 1669.

Recently the importance in nephrology of phosphorus as phosphate has been highlighted by chronic renal failure patients, in whom the toxic effect of phosphate is widely acknowledged, given the association of phosphate serum level with cardiovascular risk. This association is not limited to chronic renal failure and hemodialysis patients as high serum phosphate. Recently high serum phosphate levels were associated with increased risk for cardiovascular disease in subjects free from chronic kidney disease, and cardiovascular disease as well, and with progression of atherosclerosis. It is useful to know the history of phosphorus from its discovery in 1669, because that history gives us more evidence to better understand the negative and/or toxic effects of high phosphate serum levels and to identify phosphorus as a physiologically crucial anion.

Salivary phosphorus and phosphate content of beverages: implications for the treatment of uremic hyperphosphatemia.

BACKGROUND: Hyperphosphatemia provides relevant and dangerous evidence of end-stage renal disease (ESRD) in patients undergoing periodic hemodialysis. The relationship between hyperphosphatemia and cardiovascular calcification, with the consequences of high morbidity and mortality after cardiovascular events, is well-defined. Hyperphosphatemia is treated by dietary limitation of phosphorus ingestion and by phosphate binders, but only half of ESRD patients fall within the range of K/DOQI guidelines. OBJECTIVE AND METHODS: We summarize the results of our studies on salivary phosphate secretion in hemodialysis (HD) and chronic kidney disease (CKD) patients, and on the habit of HD patients to drink beverages with a high or low phosphate content. We also examine the correlation between hyperphosphoremia and the phosphate content of common beverages consumed by HD patients. RESULTS AND CONCLUSIONS: Higher levels of salivary phosphate secretion were found in HD and in CKD patients, along with a relationship between serum phosphorus levels and a high phosphate content of beverages in HD patients.

Phosphate salivary secretion in hemodialysis patients: implications for the treatment of hyperphosphatemia.

BACKGROUND/AIMS: Hyperphosphatemia is recognized as contributing to the increased risk of cardiac death in end-stage renal disease (ESRD) and hemodialysis (HD) patients. Currently available pharmacologic treatment for hyperphosphatemia is based on phosphate binders but, despite treatment, only half of the patients fall within the range for serum phosphorus of the K/DOQI guidelines. Therefore, there is a need to identify other therapeutic approaches in order to reduce serum phosphate. Salivary fluid contains phosphate which, if related to the daily salivary secretion (1,000-1,880 ml), may raise interest in order to identify further additive approaches to phosphorus removal in uremic patients, while data about salivary phosphate secretion in ESRD patients are controversial. METHODS: This study evaluates salivary phosphate secretion in 68 HD patients compared with 30 healthy subjects. Saxon's test confirmed normal salivary function in patients and controls. Salivary calcium and serum phosphate, calcium and PTH were also measured. RESULTS: HD patients had significantly higher salivary phosphorus levels compared with healthy controls: 30.35 (26.5-34.6) vs. 12.1 (10.58-14.73) mg/dl (p < 0.0001), and this significantly correlated (p < 0.0001) with serum phosphorus. Multiple regression analysis confirmed serum phosphorus as the only predictor (p < 0.0001) of salivary phosphorus. CONCLUSIONS: Given the functional secretive similarity between salivary glands and the kidneys, this increased salivary phosphate secretion might be interpreted as being compensatory in the presence of renal failure. Absorption of the increased salivary phosphate secretion, however, may worsen hyperphosphatemia; therefore, the binding of salivary phosphate might be considered as a further therapeutic approach to hyperphosphatemia in ESRD.