Phosphorus May Induce Phenotypic Transdifferentiation of Vascular Smooth Muscle Cells through the Reduction of microRNA-145.

Phosphorus is a vital element for life found in most foods as a natural component, but it is also one of the most used preservatives added during food processing. High serum phosphorus contributes to develop vascular calcification in chronic kidney disease; however, it is not clear its effect in a population without kidney damage. The objective of this in vivo and in vitro study was to investigate the effect of high phosphorus exposure on the aortic and serum levels of miR-145 and its effect on vascular smooth muscle cell (VSMCs) changes towards less contractile phenotypes. The study was performed in aortas and serum from rats fed standard and high-phosphorus diets, and in VSMCs exposed to different concentrations of phosphorus. In addition, miR-145 silencing and overexpression experiments were carried out. In vivo results showed that in rats with normal renal function fed a high P diet, a significant increase in serum phosphorus was observed which was associated to a significant decrease in the aortic α-actin expression which paralleled the decrease in aortic and serum miR-145 levels, with no changes in the osteogenic markers. In vitro results using VSMCs corroborated the in vivo findings. High phosphorus first reduced miR-145, and afterwards α-actin expression. The miR-145 overexpression significantly increased α-actin expression and partially prevented the increase in calcium content. These results suggest that miR-145 could be an early biomarker of vascular calcification, which could give information about the initiation of the transdifferentiation process in VSMCs.

Bone and mineral metabolism at 55 haemodialysis centres in Lima. / Influencia de la sobrecarga de calcio sobre el metabolismo óseo y mineral en 55 centros de hemodiálisis de Lima.

BACKGROUND: Mineral and bone metabolism disorders are common complications in haemodialysis patients that present significant geographical variability. OBJECTIVES: The objective of this study was to assess these disorders for the first time in haemodialysis patients from Peru. METHODS: The study included 1551 haemodialysis patients from 55 centres affiliated with the Social Health System of Peru in the city of Lima. Demographic data, comorbidities, treatments and biochemical parameters were collected from each patient. Serum calcium, phosphorus and PTH levels were categorised according to the recommended ranges in the KDOQI and KDIGO guidelines. RESULTS: The mean age of the patients was 59.5±15.6 years, with a mean time on haemodialysis of 58.0±54.2 months. All patients were dialysed with a calcium concentration in the dialysis fluid of 3.5 mEq/l and 68.9% of patients were prescribed phosphate-binding agents (98.4% of them calcium carbonate). A high percentage of patients showed serum calcium above, and serum phosphorus below, the recommended ranges in the KDOQI guidelines (32.8% and 37.3%, respectively). More than half of the patients had serum PTH values below the recommended ranges of both the KDOQI and KDIGO guidelines (56.4% and 51.6%, respectively). CONCLUSIONS: Patients included in this study were younger than those from other studies and showed both hypophosphataemia and suppressed PTH, probably due to an excessive calcium overload through dialysis fluid and the use of calcium-containing phosphate binding agents.

The clinical impact of aluminium overload in renal failure.

Chronic aluminium exposure and toxicity related to aluminium absorption and contaminated dialysis fluid continue to be a problem for many patients with renal failure, particularly in South America and in some developing countries. The two most prevalent sources of aluminium in this population are water used to prepare dialysate and aluminium-containing phosphate binders. Of particular concern is the effect of aluminium at the level of the bone, the haematopoietic system and the brain. Here we focus mainly on the adverse effects of aluminium on bone, the preferred organ of aluminium accumulation in the body. Unfortunately, aluminium has a cumulative effect, thus even short-term exposure to aluminium in phosphate binders adds to the total load and may contribute to the risk of aluminium-related bone disease. Even a bone biopsy does not allow a precise determination of total bone aluminium content. We examine the mechanisms by which aluminium contributes to abnormal bone remodelling. Studies indicate that aluminium has a direct effect, inhibiting bone formation and resorption. There is also evidence for an indirect effect through the action of aluminium on parathyroid hormone synthesis and by its modulation of calcium activity. We discuss commonly used techniques for identifying aluminium load and review studies of chelation therapy as a method to lower aluminium load. It is apparent that aluminium overload has serious consequences for patients with chronic renal failure, yet this problem can be largely prevented by the use of aluminium-free phosphate binders. The deleterious effects on bone remodelling caused by chronic exposure to aluminium suggest that caution should be observed when using other metals as phosphate binders.