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El sevelamer es un captor no cálcico de fósforo que se utiliza en la ERC avanzada y en diálisis para el control de la hiperfosforemia. Varios estudios experimentales, observacionales y ensayos clínicos han mostrado que el sevelamer tiene efectos pleiotrópicos, más allá del control de la hiperfosforemia, incluyendo acciones sobre la inflamación, el estrés oxidativo, el perfil lipídico y la aterogénesis, la calcificación vascular, la disfunción endotelial y la disminución de diversas toxinas urémicas, todo lo cual sería la base biológica de su efecto global sobre la morbilidad y la mortalidad cardiovascular en pacientes con enfermedad renal crónica. En esta revisión, se hace énfasis en estas acciones pleiotrópicas del sevelamer y su impacto en la salud cardiovascular, con la experiencia publicada después de más de 10 años de experiencia clínica.

Sevelamer is a non-calcium phosphate binder used in advanced chronic kidney disease (CKD) and in dialysis for hyperphosphataemia control. Several experimental, observational studies and clinical trials have shown that sevelamer has pleiotropic effects, beyond hyperphosphataemia control, including actions on inflammation, oxidative stress, lipid profile and atherogenesis, vascular calcification, endothelial dysfunction and the reduction of several uremic toxins. This is the biological basis for its global effect on cardiovascular morbidity and mortality in patients with chronic kidney disease. This review focuses on these pleiotropic actions of sevelamer and their impact on cardiovascular health, with the experience published after more than ten years of clinical expertise., (Copyright © 2015. Published by Elsevier España, S.L.U.)

The purpose of this case report is to describe the regression of vascular calcifications (VC) in a patient with secondary hyperparathyroidism (SHPT) after having added cinacalcet to her treatment. We present the clinical case of a 48-year-old woman with chronic renal failure secondary to tubulointerstitial disease. She was being treated with long-term haemodialysis (HD) and underwent two kidney transplants with transplantectomies. The patient presented with severe SHPT caused by parathyroid gland hypertrophy. The radiology test showed signs of VC in the radial and interdigital arteries, and VC in a linear arrangement were observed in both breasts on the mammography. Cinacalcet was added to her treatment with vitamin D derivatives and phosphate-binding agents, which resulted in a good control of mineral metabolism. The radiology test showed that the calcification in the interdigital artery had disappeared and that the bone appeared to be more structured. The mammography also showed regression of the VC. To conclude, cinacalcet may have potential for regression of VC in patients with SHPT.

Introduction: Non-adherence to phosphate binding (PB) medication may play a role in the difficulty in achieving the targets for phosphorus. We have a wide armamentarium of PB but preferences of patients are poorly understood., Objective: to study the patients' preferences and beliefs regarding PB and their influence on adherence and serum phosphate., Methods: A cross-sectional cohort study was performed. A total of 121 hemodialysis patients answered a specific questionnaire in which they were questioned about adherence, the type of PB they preferred and the reasons for their choice. All patients questioned tasted two or three PB. The consequence of non-adherence to PB was estimated indirectly by determination of serum phosphorus., Results: Specific noncompliance with PB medication was recognized by 21.4% of patients. Patients non-adherent specifically to PB were more likely to have P levels >5.5 mg/dl (χ(2): 4.7; 95% CI 1.07-6.5; p = 0.03). Paradoxically, patients non-adherent showed greater knowledge of the use (χ(2): 17.3; 95% CI -2.2-10.1; p <0.0001) and importance of the drug (χ(2): 10.4; 95% CI -1.5-6.6; p = 0.001). The percentage of patients prescribed binders they did not like was 54.5%. Patients who were taking PB they did not like had a greater risk of having P levels >5.5 mg/dl) (χ(2): 13.3; 95% CI -1.1-1.5; p = 0.0001). Calcium acetate was the preferred PB in 47.1% of patients, lanthanum carbonate in 40%, sevelamer in 20.6% and aluminum hydroxide in 19.4%. The reasons claimed by patients for their negative ratings of PB were the type of dosage form, the taste, the number of tablets and gastric intolerance. Gastric intolerance and bad taste were more frequent in aluminum hydroxide patients (19.4% and 22.2%, respectively). Sevelamer received complaints about its dosage form because the tablets were too large and a large number of tablets were required (27.2%). 17.7% of patient who were taking lanthanum carbonate did not like the chewable tablets., Conclusion: patients who were taking binders that they did not like had worse serum P levels and were prescribed higher doses of binders. Knowing patients' preferences about the drugs prescribed may be a key factor in achieving adequate adherence to treatment.

Sevelamer use has a high prevalence, and half of patients are treated with this noncalcium binder. Two randomized studies appeared in 2007 that compared the efficacy of sevelamer over calcium salts. In the more statistically potent of the two studies, no differences were found in mortality between the sevelamer and calcium groups, except for a benefit in favor of sevelamer in patients older than 65 years. In the other less statistically potent study, lower mortality was observed in the sevelamer group. Both studies have various deficiencies and a timely meta-analysis of the two studies appearing that same year concluded that there was no significant evidence demonstrating a superior efficacy of sevelamer over calcium salts. Therefore, generalized extension of its use as a first-line binder is not recommended. However, its use can be assessed in specific clinical situations. With regard to the cost-benefit ratio, as there is no evidence that greater clinical benefits are obtained with sevelamer than with calcium salts, prudence and moderation in its use are needed because of the high cost/benefit ratio demonstrated. Otherwise, we will contribute to increasing the already very high treatment cost in these patients, with one of the highest costs per life year gained in medicine. The cost/benefit ratio of sevelamer remains unattractive from an economic point of view, even if dialysis and transplant are excluded in these patients.

Hyperphosphatemia is a complication that appears in the early stages of chronic kidney disease (CKD) and that has been shown to have serious consequences in kidney disease patients. New phosphate regulators are currently being studied such as FGF- 23, a counter-regulatory phosphaturic hormone for vitamin D, and klotho, a cofactor necessary for activation of FGF-23. The main consequences of hyperphosphatemia described in CKD patients not on dialysis are ectopic calcification, increased mortality and more rapid progression of CKD. All this indicates the need for strict control of Pi. The two most currently used drugs for this purpose are lanthanum carbonate and sevelamer. Although there are no studies specifically designed for this predialysis population, these drugs appear to be effective and safe. Another complication of CKD is vitamin D deficiency which, according to recently published studies, is more prevalent and appears in earlier stages of the disease than was initially thought. There is wide debate on the need to administer vitamin D supplements systematically due to the pleiotropic effects of this hormone and which are unrelated to development of renal bone disease. Because of these doubts, there is no agreement on routine administration, although there is consensus on the need to measure 1,25-dihydroxyvitamin D and 25-hydroxyvitamin D values and to wait for the result of numerous studies that are being carried out on the impact of vitamin D on progression of cardiovascular risk factors in CKD and the possible consequences of its indiscriminate administration.

The articles providing answers to the questions on vascular calcification of most interest from a clinical point of view were selected. 1. How is it measured?: Studies showing the clinical utility of different tools to quantify it were analyzed. 2. What does it measure?: Both in dialysis patients and the general population, vascular calcification and arterial stiffness are prognostic factors for morbidity and mortality. Other markers such as fetuin-A are associated with mortality in patients on hemodialysis but not in patients in early stages of chronic kidney disease. 3. What causes it?: In two selected studies, it was demonstrated again that low bone turnover and diabetes cause cardiovascular disease and vascular calcification, respectively. 4. How is it treated?: There is still no clinical evidence of regression of vascular calcification. However, a prospective study in new hemodialysis patients showed that sevelamer compared to calcium compounds slows the progression of vascular calcification and confers greater survival. A study comparing both compounds in chronic hemodialysis patients showed that sevelamer only had a benefit on survival in patients older than 65 years. It remains to be demonstrated whether the good experimental results of paricalcitol and cinacalcet are confirmed in prospective clinical studies.

The rate of oxalate absorbed from intestine is highly influenced by calcium intake in healthy subjects. It is unknown whether commonly used phosphate binders modify intestinal absorption and renal excretion of oxalate in chronic kidney disease (CKD) patients. This study aims to determine if calcium carbonate or sevelamer influences on urinary oxalate excretion. Twenty patients with CKD (stage 4 and 5 pre-dialysis) were included. Two treatment (1500 mg of calcium carbonate or 2400 mg of sevelamer), two-period (21 days each), crossover study with balanced assignment of the order of administration, and two washout periods were the main characteristics of this study design. Laboratory analyses in each phase included: serum creatinine, calcium, phosphorus, bicarbonate, total cholesterol, and 24 h urinary excretion of oxalate, creatinine, and urea. Creatinine clearance, protein catabolic rate (PNNA), total urinary oxalate excretion, and urinary oxalate / creatinine ratio were determined. Seventeen patients completed both treatment sequences. Total urinary oxalate excretion and urinary oxalate / creatinine ratios decreased significantly with respect to washout periods either after sevelamer or calcium carbonate treatment. The decrease in urinary oxalate excretion was greater after calcium carbonate (41.2+/-17.4%) than after sevelamer treatment (30.4+/-23.8%). There were not significant changes in renal function or PNNA values throughout the study periods. In conclusion, either calcium carbonate or sevelamer significantly reduces urinary oxalate excretion in CKD patients. Further studies will be needed to ascertain whether the type of phosphate binder influences on the accumulation of oxalate in CKD patients.

Secondary hyperparathyroidism (SHP) is still an early and frequent complication of chronic renal disease (CRD). Currently, CRD is an independent cardiovascular risk factor, and calcium-phosphorus metabolism is one of the modifiable related factors. In this first article, we summarize the recent SHP treatment paradigm shift in dialysis patients, derived from the better knowledge and understanding of vascular calcification. We analyze the most recent guidelines (K/DOQI), and describe the general implications of hyperphosphatemia, as well as our therapeutic approach with phosphorus-binders. Since sevelamer additionally presents some pleiotropic effects and it attenuates the progression of vascular calcification, we consider it in the first-line of treatment despite it is not yet demonstrated a survival benefit. We also minimize the use of elemental calcium to a maximum of 1000 to 1500 mg/day. Lanthanum carbonate may well be an important therapeutic agent in the near future, especially if security concerns related to metal accumulation are overcome. Ferric citrate, colestilan and nicotinamide may soon play a role. All these drugs, isolated or in combination, are important in the treatment of SHP since a great deal of its success and the avoidance of some dialysis-related complications depend on an efficient phosphorus control.

Unlabelled: Sevelamer is a recent phosphate binder that is mineral-free, and represents a great advance in the treatment of hyperphosphatemia in patients with hypercalcemia and/or gastric intolerance to calcium-based phosphate binders. The communications about the experience with the use of sevelamer in patients non-yet in dialysis is scanty. The aim of our study is to investigate retrospectively the gastrointestinal tolerance of sevelamer, their efficacy as phosphate binder and other parameters in a group of 89 patients with chronic renal failure in predialysis. We have analysed the effects of sevelamer at baseline and after 1, 3 and 6 months on the following data and parameters: calcium, phosphate, intact PTH, venous bicarbonate, urea, creatinine, creatinine clearance, side-effects, number of patients that were discontinued, and co-treatment during the study period with phosphate-based binders, calcitriol, lipid-lowering drugs and sodium bicarbonate., Results: 19 patients (21.3%) refused to continue with sevelamer at the first month (16 patients had digestive intolerance and 3 several symptoms). Serum phosphate fell at 3 months (5 +/- 0.8 mg/dl basal vs 4.8 +/- 0.7 mg/dl, p = 0.02) and 6 months (5 +/- 0.8 mg/dl basal vs 4.7 +/- 0.9 mg/dl, p = 0.07). Serum calcium fell at 6 months (9.8 +/- 0.7 mg/dl basal vs 9.4 +/- 0.6 mg/dl, p = 0.03). Venous bicarbonate and iPTH were unchanged, but the quantity of sodium bicarbonate administered increased significantly. Blood cholesterol fell at 1 months (193 +/- 49 mg/dl basal vs 173 +/- 52 mg/dl, p = 0.001) and 3 months (205 +/- 49 mg/dl basal vs 170 +/- 49 mg/dl, p = 0.004), in spite of a significant reduction of the dose of statins., Conclusions: Sevelamer is an effective phosphate binder in predialysis patients and also reduces significantly the serum cholesterol, improving the blood lipid profile. The levels of venous bicarbonate remained unchanged, at expenses of an increment in the dose of sodium bicarbonate supplementation.

Background: Sevelamer is a non-absorbable phosphorus chelator that is not a source of aluminium, calcium or base. The clinical experience with sevelamer in peritoneal dialysis and in daily clinical practice is scarce. The aim of this study is to evaluate the results of therapy of hyperphosphoremia with sevelamer on serum phosphorus and phosphorus chelators requirements, in a peritoneal dialysis clinical practice., Methods: Sevalamer 400 mg was prescribed to peritoneal dialysis patients with hyperphosphoremia who were treated with aluminium hydroxide or with calcium salts in the absence of hypocalcemia. Fourteen patients completed 12 months of therapy., Results: The initial sevelamer dose was 2,280 +/- 760 mg/day, and was increased to 2,760 +/- 1,160 mg/day at 12 months. At 12 months no patient was on aluminium salts and calcium salts had been significantly reduced. Phosphoremia (5.9 +/- 0.6 to 5.0 +/- 1.4 mg/dL, p = 0.049), calcium-phosphorus product (59.8 +/- 5.8 to 48.6 +/- 12.5 mg2/dL2, p = 0.01) and serum cholesterol (191 +/- 29 to 167 +/- 33 mg/dL, p = 0.02) decreased at 12 months. No significant changes were observed in serum triglycerides, total CO2 or PTH. Serum alkaline phosphatase increased at 6 months, but values returned to normal at 12 months. No changes were observed in serum gamma-glutamyl-transpeptidase. Five patients were started on 1.25 (OH)2 vitamin D therapy., Conclusion: In peritoneal dialysis patients, sevelamer allows a satisfactory control of serum phosphorus levels and calcium-phosphorus product, while decreasing the amount of aluminium and calcium salts prescribed.

Phosphorus is involved in the pathogenesis of hyperparathyroidism in Chronic Renal Failure (CRF) and in extra-osseous calcifications. Therefore, it is directly related with the morbi-mortality of these patients. The control of phosphorus is of the utmost importance and is often extremely difficult to achieve. A quick overview of the drugs that can bind phosphorus is given in this paper. Iron salts are beginning to come through as a viable possibility in the near future; nevertheless, calcium salts continue to be the most widespread. The problem is the ease with which a positive calcium balance can be produced, as extra-osseous calcifications (and above all, vascular calcifications) can appear and morbid-mortality increases. As a result of all this, calcium-free binders such as lanthanum carbonate and sevelamer are eagerly awaited. The lanthanum is as of yet little and not very well known. Sevelamer possesses good phosphorus-binding properties, as it is insoluble, does not cause intestinal degradation, does not contain traces of other elements and its use has few side effects. Long-term studies and accumulated experience have demonstrated its efficacy as a binder, plus additional advantages such as an improvement in the lipid profile, with a decrease in LDL--and an increase in HDL-cholesterol. As to whether these new binders--or any other compounds that could appear-will be of any real use only time will tell.