Dose Of Sevelamer Research Articles

#313 Enhanced urinary phosphorous reduction: comparative study of oxylanthanum carbonate and tenapanor in rat

Abstract Background and Aims End-stage renal disease (ESRD) affects >7 M people worldwide and ∼70% of patients with ESRD have hyperphosphatemia. Oxylanthanum carbonate (OLC) is a novel nanotechnology product that combines lanthanum, which has the highest binding capacity vs other phosphate (P) binders, with a smaller pill size that is swallowed with water vs chewed. Tenapanor is a sodium hydrogen exchanger inhibitor used to reduce serum P in adults with chronic kidney disease (CKD) on dialysis. A previous study conducted by King et al found that when administered together, tenapanor and sevelamer decreased urinary p excretion significantly more than either tenapanor or sevelamer alone across all sevelamer dose levels. Employing an identical study design and dosing regimen, the objective of our study was to evaluate the effects of tenapanor and OLC on P excretion. Method In our study, we utilized the study design and dosage regimen from King et al involving sevelamer and tenapanor. 64 male Sprague Dawley rats were fed standard chow 1 week prior to study start. On study day −1, animals were randomized into 3 study groups (n = 8): 1) vehicle, 2) tenapanor 0.15 mg/kg, 3) Vehicle + OLC 0.75%, 4) Vehicle + OLC 1.5%, 5) Vehicle + OLC 3%, 6) tenapanor 0.15 mg/kg + OLC 0.75%, 7) tenapanor 0.15 mg/kg + OLC 1.5%, and 8) tenapanor 0.15 mg/kg + OLC 3%. Vehicle and tenapanor were dosed PO twice/day whereas OLC was incorporated into the diets. 24-hour urine samples were collected using metabolic cages on day 9, 10, and 11 for urinary P measurements. Results Compared to vehicle alone (group 1), P reduction of tenapanor (group 2) was 8.5 mg/day (not significant), while P reduction of OLC (group 5) was 25.3 mg/day (significant). OLC had 16.8 mg/day more P reduction than tenapanor (Fig. 1). Conclusion OLC demonstrated 3x more effective urine P reduction vs tenapanor. Subsequent analyses will focus on examining the combination of tenapanor and OLC. Combining OLC and tenapanor utilizes 2 different mechanisms of action to manage P levels while having a low pill burden, which may lead to synergistic effects to be investigated in future studies.

Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis

Introduction: Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association. Methods: Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (vs. non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups. Results: Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.91–1.06) or all-cause mortality (220 vs. 224 events per 1,000 person-years; IPTW-HR: 0.98, 95% CI: 0.93–1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization. Conclusion: Among patients requiring hemodialysis, sevelamer (vs. non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.

Selamerex: regional real-world practice and perspective of therapy optimisation

Перенести в английский вариант BACKGROUND. Hyperphosphatemia in CKD is spread widely, represents as independent factor of mortality at all stages of CKD, after transplantation, reduces the effectiveness of nephroprotection, leads to vascular calcification, stimulates hyperparathyroidism. Achieving the phosphatemia target is a difficult task and is based on a combination of a hypophosphate diet, effective dialysis, the antihyperparathyroidic measures and the phosphate-binders (PBs). THE AIM. The aim is to evaluate the effectiveness of sevelamertherapy in real clinical practice as part of a hypophosphatemic strategy with clarification of the conditions and measures under which it is optimal. PATIENTS AND METHODS. In an eight-month study in a region where there are no restrictions on access to calcium-free PBs, 127 patients were included in the study after the "washing period ": the of sevelamer doses were titrated until phosphatemia reaches below 1.58 mmol/l in parallel with individual measures of four-component hypophosphatemic strategy. RESULTS. From the starting dose of 3-6 tablets/day, 38 patients experienced either dose increase (+ 1016 ± 760 mg) or in 28 patients– decrease (- 1427 ± 1059 mg). By the third month of therapy, the proportion of patients with phosphatemia < 1.58 mmol/l reached 70 %, < 1.78 mmol/l – 90 %. The decrease magnitude depended on the initial phosphatemia, the level of PTH (maximum in the range of 150-600 pg/ml), occurs more slowly in men. During therapy, there was a decrease in the need for antihyperparathyroid therapy in the absence of dynamics in the parathyroid hormone level. In multiple regression analysis models, the independent factors associated with phosphatemia during treatment were sevelamer dose, dialysis dose, baseline phosphate and parathyroid hormone levels; the magnitude of phosphatemia reduction was independently associated with sevelamer dose, dialysis dose, baseline parathyroid hormone level, and assessment of treatment compliance. CONCLUSION. Sevelamer in a moderate well–tolerated doses as part of an individualized hyperphosphatemia correction strategy is able to achieve target phosphatemia (< 1.58 mmol/L) in 70 % of cases, and relatively safe level (< 1.78 mmol/L) – in 90 %.

A Retrospective Single-Center Study of Sevelamer Hydrochloride for the Treatment of Hyperphosphatemia in Children With Tumor Lysis Syndrome.

Introduction Tumor lysis syndrome (TLS) is a life-threatening metabolic abnormality. The incidence of TLS depends on the underlying malignancy. In a recent analysis of hematological malignancy, the incidence of clinical TLS in children was 3.8%, laboratory TLS 46.2%, and hyperphosphatemia 32.7%. Sevelamer is effective for the treatment of hyperphosphatemia associated with renal failure; however,there is no clear data that it has the same effect in treating hyperphosphatemiawith TLS. Methods This was a retrospective study among children aged ≤14 years with hematological malignancy who developed TLS and received sevelamer to treat hyperphosphatemia at Princess Norah Oncology Center, King Abdulaziz Medical City (KAMC) in Jeddah from January 2012 to December 2016. Results A total of 34 patients received sevelamer. The majority was male (64%), with a median age of six years. The median sevelamer dose per day was 1600 mg, while the median duration of use was two days. Phosphate level was significantly decreased at different times(24 hours, 48 hours, and 72 hours) during sevelamer usage, p-value <0.001. Conclusion In our study, the use of sevelamer resulted in a significant decrease in phosphate levels. This finding further consolidates the efficacy of sevelamer in treating hyperphosphatemia with TLS. However, further research into the drug's kinetics is recommended.

Binding and inhibitory activities: A novel oral therapeutic agent for the treatment of hyperphosphataemia rats

Novel oral therapeutic agents based on inhibition or binding activity without adverse events in CKD patients are urgently needed. Here, 5/6 nephrectomy (NX) rats were used to construct a CKD model. Aminated cellulose (AC711), which is metal-free, non-absorbable, and low-volume expansive, was used as a novel oral therapeutic agent for hyperphosphataemia treatment in rats. The efficacy of AC711 on serum and urinary phosphate levels, the expression of type II sodium-dependent phosphate cotransporter (NPT2b), and type III Na-dependent phosphate cotransporter (PiT-1/2) was examined. Serum fibroblast growth factor-23 (FGF-23) levels, parathyroid hormone (PTH) levels, and the phenotypic transformation of vascular smooth muscle cell markers (smooth muscle 22 (SM22) and Runx2) are considered an adaptive response to elevated serum phosphate levels. A similar efficacy of AC711 was observed on serum and urinary phosphate levels when the same dose of AC711 and sevelamer was administered to 5/6 NX rats. The decreasing expression of NPT2b, PiT-1, and PiT-2 was examined in the AC711 groups in a dose-dependent manner. The sevelamer and AC711-MD groups for FGF-23 and PTH indicated no significant difference. The down-regulation of Runx2 expression and up-regulation of SM22 expression were seen in the AC711 groups in a dose-dependent manner. Two suppression mechanisms (binding and inhibiting activities) were observed in the gastrointestinal (GI) tract in the AC711 groups. A novel oral phosphate binder, AC711, showed both binding and inhibition characteristics. The low-volume expansion of AC711 following exposure to simulated intestinal fluid provides the potential therapeutic benefits with the advantage of moderate GI side effects.

MO543: Efficacy and Influence on the Key Indicators of Mineral-Bone Disorders of the Sucroferric Oxyhydroxide and Sevelamer Carbonate in Hemodialysis Patients

Abstract BACKGROUND AND AIMS Currently, the effectiveness of phosphate-binding agents in patients with CKD should be determined not only by the level of reduction in hyperphosphatemia, but also by the effect on other key factors involved in the development of CKD-MBD. The results of the effect of phosphate binders on the parameters of CKD-MBD, excluding phosphate, are unclear. Our prospective randomized controlled trial evaluated the effect of 16-week treatment with sucroferric oxyhydroxide versus sevelamer carbonate (‘sevelamer’) on the parameters of CKD-MBD in patients with hyperphosphatemia on programmed hemodialysis. METHOD A total of 50 stable patients with hyperphosphatemia (P ˃ 5.5 mg/dL) after a 4-week washout period, were randomized at a 1:1 ratio to receive sucroferric oxyhydroxide (n = 25) or sevelamer (n = 25) for treatment up to 16 weeks. In all patients were monthly evaluated levels of FGF23, soluble Klotho, c-reactive protein (CRP), hemoglobin (Hb), ferritin, transferrin saturation, phosphorus (P), calcium (Ca), parathyroid hormone (PTH). The dose of both medications was adjusted according to serum phosphate. RESULTS The average intact fibroblast growth factor 23 (FGF23), PTH, transferrin saturation and ferritin levels did not significantly change in both groups. Meanwhile, Klotho levels increased by 25% in the sucroferric oxyhydroxide group (P &amp;lt; 0.05). We observed a significant decrease in serum phosphate level from 6.8 ± 1.5 to 5.27 ± 0.99 mg/dL (P &amp;lt; 0.01) only in the group with sucroferric oxyhydroxide. However, treatment with sevelamer did not decrease the level of P: 6.32 ± 1.5 versus 6.35 ± 1.9 mg/dL by the end of the study. The number of prescribed tablets was lower in the sucroferric oxyhydroxide group (2.0 ± 1.5 tab/day, mean ± SD) compared with sevelamer group (6.1 ± 3.2 tab/day, mean ± SD). We noted also in group sucroferric oxyhydroxide an increased Hb level from 105.6 ± 15.7 to 111.9 ± 22.3 g/L (P &amp;lt; 0.05) and a simultaneous decrease of CRP level by 50% (P &amp;lt; 0.01). CONCLUSION Treatment with sucroferric oxyhydroxide significantly increased Klotho and Hb levels and lowered CRP levels. Sucroferric oxyhydroxide was more effective in lowering phosphorus levels than sevelamer, which can be explained by an insufficient dose of sevelamer and a short treatment period.

Randomized Crossover Trial of Phosphate-binding Medication on Serum Phosphate Levels in Patients With Aortic Stenosis

PurposeAortic stenosis is a common cause of valvular heart disease with no means of prevention. The recognized association between aortic stenosis and serum phosphate raises the possibility of preventing progression of the disorder by using phosphate-binding drugs, but there is uncertainty whether such treatment lowers serum phosphate levels in patients without diagnosed renal failure. This pilot study was conducted to answer this question in patients with aortic stenosis. MethodsA randomized, double-blind, crossover trial of the phosphate-binding drug sevelamer was conducted in 72 patients. Patients were prescribed sevelamer 0.8 g (low-dose), sevelamer 2.4 g (high-dose), and matching placebo, 3 times daily with food; each regimen lasted 6 weeks and was allocated at random. Serum phosphate levels were measured at the end of each treatment period, and within-person levels were compared. FindingsSixty-one patients completed the 3 treatment periods. There was no significant difference in the mean end-treatment phosphate levels across all patients (3.38, 3.36, and 3.31 mg/dL with placebo, low-dose sevelamer, and high-dose sevelamer, respectively). Post hoc analysis showed a reduction in phosphate levels with increasing sevelamer dose in the highest baseline phosphate quartile group; a 0.3 mg/dL reduction (mean, 4.09 mg/dL with placebo, 3.95 mg/dL with low-dose sevelamer, and 3.79 mg/dL with high-dose sevelamer; Ptrend = 0.027). ImplicationsSevelamer had no overall statistically significant effect in lowering serum phosphate levels, but a reduction was observed in patients with phosphate levels in the highest quartile group of the population distribution. This hypothesis-generating result requires confirmation in an independent study. If confirmed, a trial of sevelamer in preventing the progression of aortic stenosis may be justified in patients with high phosphate levels. ISRCTN Registry identifier: ISRCTN17365679.

250 Lower Serum Phosphorus (sP) and Pill Burden Among Hyperphosphatemic Hemodialysis (HD) Patients Prescribed High Doses of Sevelamer (Sev) and Switched to Sucroferric Oxyhydroxide (SO): An Observational Study.

250 Lower Serum Phosphorus (sP) and Pill Burden Among Hyperphosphatemic Hemodialysis (HD) Patients Prescribed High Doses of Sevelamer (Sev) and Switched to Sucroferric Oxyhydroxide (SO): An Observational Study.

Phosphate binders as a cause of hypothyroidism in dialysis patients: practical indications from a review of the literature

BackgroundAlthough fatigue is common in dialysis patients, polypharmacy is seldom listed among its causes. In this report, we describe a dialysis patient who developed severe fatigue due to pharmacological interaction between two commonly prescribed drugs, phosphate binders and levothyroxine.Case PresentationA 65-year old woman, on dialysis for 17 years, complained of fatigue (weight 54 Kg, height 1.55 m, BMI: 23 Kg/m2; malnutrition inflammation index: 10; Charlson index 9). She had been treated with lithium for about 20 years. A heavy smoker, she was obese and diabetic when young, but stopped treatment after weight loss. She had undergone thyroidectomy for papillary carcinoma, left hemicolectomy for colon adenocarcinoma, left quadrantectomy followed by radiotherapy for ductal mammary adenocarcinoma, subtotal parathyroidectomy for tertiary hyperparathyroidism. At the time of this report, she was on thrice-weekly hemodiafiltration (Daugirdas 2 Kt/V: 1.6–1.8). Her recent treatment included spironolactone, amlodipine, perindopril, valproate, lamotrigine, levothyroxine, vitamin D, calcium carbonate, sodium polystyrene and sevelamer. After she questioned her doctor about whether her fatigue might be the result of a drug interaction, levothyroxine interference was identified (TSH, previously normal, increased to 13.07 mU/L, after increasing sevelamer dose, and normalized after change of drug schedule).Literature review: only 5 relevant papers on levothyroxine and phosphate binders on dialysis were found on Pubmed and EMBASE (out of 351 titles retrieved). Information was therefore inferred from studies in normal volunteers or in other diseases.Discussion and conclusionsOur case differs from other reports on lower TSH at diagnosis, underlining the need for awareness of the importance of early diagnosis. Integrating the scant literature on dialysis patients with data available in the general population, some working conclusions can be reached: while all phosphate binders potentially interfere with levothyroxine absorption, interference seems to be highest for sevelamer; interference is limited but not excluded by increasing the intervals between drugs; morning fast is usually indicated but, when clashing with the timing of other drugs, a bedtime dose and liquid preparations may be indicated. In the absence of an agreed control schedule, our case supports close monitoring of TSH (1–3 months if unstable, twice-yearly in stable patients).

Linkage of Fibroblast Growth Factor 23 and Phosphate in Serum: Phosphate and Fibroblast Growth Factor 23 Reduction by Increasing Dose of Sevelamer.

BackgroundHigh serum phosphate and fibroblast growth factor-23 (FGF-23) levels are well-recognized independent risk factors of mortality and morbidity in patients with chronic kidney diseases (CKDs). Sevelamer, as a phosphate chelating agent, reduces serum phosphate and FGF-23 levels produced by bone osteocytes. This study aimed to determine the best dose at which sevelamer could successfully reduce serum phosphate and FGF-23 levels in rat models of adenine-induced CKD.MethodsCKD was induced using adenine. Healthy and CKD-induced rats were divided into 6 groups as follows: healthy controls; CKD controls; rats treated with 1%, 2%, and 3% sevelamer for CKDs; and healthy rats administered 3% sevelamer. Biochemical factors and serum FGF-23 levels were measured using spectrophotometry and enzyme-linked immunosorbent assay methods.ResultsSerum phosphate levels were best decreased in rats receiving 3% sevelamer in their diet (5.91±1.48 mg/dL vs. 8.09±1.70 mg/dL, P<0.05) compared with the CKD control rats. A dose-dependent decrease in serum FGF-23 levels was observed, and the most significant results were obtained in rats receiving 3% sevelamer compared with the CKD control rats (142.60±83.95 pg/mL vs. 297.15±131.10 pg/mL, P<0.01).ConclusionsHigher sevelamer doses significantly reduced serum phosphate and FGF-23 levels in adenine-induced CKD rats.

Gastrointestinal complications induced by sevelamer crystals.

BackgroundSevelamer is a phosphate binder widely used in chronic kidney disease (CKD) patients. Sevelamer, as well as other resin-based binders, can crystallize leading to the formation of concretions. Sevelamer crystals (SC) have been associated with gastrointestinal (GI) mucosal injury. We describe three new cases of GI lesions associated with SC and review previously reported cases.MethodsWe describe three new cases of GI lesions associated with SC and review previously reported cases.ResultsWe found 16 previously reported cases of SC-induced GI lesions. The mean patient age was 61 years (interquartile range 51.5–71.75), 62.5% were females and 10 patients were diabetic. In 13 cases, SC was found inside the GI mucosa. Six patients had history of major abdominal surgery. GI bleeding was the most common clinical symptom (n = 7), with three patients presenting with acute abdomen requiring surgical intervention. Although, SC-induced lesions were observed in all GI segments, intestine was involved in 81% of the cases. Endoscopic examination revealed mainly erosions and ulcerations (n = 7) and pseudoinflammatory polyps (n = 5). No association between sevelamer doses and the severity of GI lesions was found. However, diabetics patients seemed to develop GI lesions with smaller doses of sevelamer as compared with non-diabetic patients, in spite of their fewer GI comorbidities.ConclusionsSC-induced GI lesions should be considered in CKD patients treated with sevelamer who present GI symptoms, especially lower GI bleeding, once other causes have been ruled out. Diabetics seem more prone to develop SC- associated GI lesions. Sevelamer therapy should be avoided if possible in patients with a history of major abdominal surgery or chronic constipation, because of the high risk of serious GI complications.

Low Dose of Sevelamer is Enough to Prevent Coronary Artery Calcification Progression in Prevalent Hemodialysis Patients

Low Dose of Sevelamer is Enough to Prevent Coronary Artery Calcification Progression in Prevalent Hemodialysis Patients

Economic evaluation of sevelamer for the treatment of hyperphosphatemia in chronic kidney disease patients not on dialysis in the United Kingdom

Objectives:To determine the cost effectiveness of sevelamer vs calcium carbonate in patients with chronic kidney disease and not on dialysis (CKD-ND) from the perspective of the National Health Service (NHS) in the UK.Methods:A Markov decision analytic model was developed to estimate (1) total life years (LYs), quality-adjusted life years (QALYs), and costs for patients treated with sevelamer or calcium carbonate; and (2) incremental costs per LY gained (LYG) and per QALY gained for sevelamer vs calcium carbonate. Data informing probability transitions to all-cause death and dialysis inception in CKD-ND patients were taken directly from the INDEPENDENT-CKD study and were extrapolated beyond the 3-year clinical trial using Weibull regression analysis. Estimates of health utility and costs (in £2011) were derived from the published literature.Results:Over a lifetime horizon, sevelamer treatment resulted in a gain of 2.05 LYs and 1.56 QALYs per patient, an increase of £37,282 in total costs per patient vs calcium carbonate (3.5% discount), and a per-patient cost of £18,193/LYG and £23,878/QALY gained. Results were robust to alternative assumptions in key parameters; results were most sensitive to alternative assumptions regarding the mean daily dose of sevelamer, impact of sevelamer on dialysis initiation, cost of dialysis, and health utility estimates. The probabilistic sensitivity analysis showed that sevelamer was cost-effective vs calcium carbonate in 93% of simulations at a willingness-to-pay threshold of £30,000/QALY gained.Limitations:While the model simulated a real-world clinical setting, this analysis was subject to limitations common to all decision analytic models, in that it used a mix of data sources and relied on several assumptions. Not all variables that impact real-world outcomes and costs were included in this model.Conclusions:Sevelamer is a cost-effective option compared to calcium carbonate for the first-line treatment of hyperphosphatemia in CKD-ND patients in the UK.

Clinical factors associated with serum copper levels and potential effect of sevelamer in hemodialysis patients

Copper is an essential mineral nutrient for humans. Serum copper levels of hemodialysis patients are higher than those of healthy subjects, but it remains to be elucidated whether increased serum copper may have harmful effects. In addition, a recent in vitro study has shown that sevelamer can adsorb copper. In the present study, we searched for clinical factors associated with serum copper levels in hemodialysis patients. This cross-sectional study included patients undergoing hemodialysis for more than 6 months. In these patients, we statistically tested associations between serum copper levels and other parameters, including nutritional markers, lipid profiles, oxidative stress, inflammation, and sevelamer administration. Among 48 patients (male/female = 28:20, age 71 ± 10 years, hemodialysis duration 84 ± 72 months), sevelamer hydrochloride was administered in 39 patients (81.3 %). In univariate analysis, serum copper levels showed significant positive correlations with serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), and malondialdehyde modified-LDL and negative correlations with plasma total homocysteine levels and the administered dose of sevelamer. In multivariate analysis, serum levels of LDL-cholesterol and hs-CRP were found to be independent determinants of serum copper levels. We found that serum copper levels were independently associated with dyslipidemia and inflammation in hemodialysis patients, but the pathogenic roles of copper remain to be elucidated. In addition, potential effect of sevelamer on serum copper levels should be examined in appropriately designed studies.

Potential influence of sevelamer hydrochloride on responsiveness to erythropoiesis‐stimulating agents in haemodialysis patients

Vitamin D analogues, cinacalcet, and sevelamer play pivotal roles in the management of chronic kidney disease-mineral bone disorder, and are noted to have pleiotropic effects. We examined whether these agents might be associated with the responsiveness to erythropoiesis-stimulating agents (ESA). In this cross-sectional study including haemodialysis patients treated with ESA, we searched for clinical parameters associated with the ESA resistance index, which was calculated as the weekly ESA dose divided by the patient's haemoglobin value. Among 45 patients (male: female = 28 : 17, age 68 ± 10 years, haemodialysis duration 84 ± 60 months), vitamin D analogue, cinacalcet, and sevelamer were used in 95.6%, 26.7%, and 84.4% of the patients, respectively. Univariate analysis showed significant association of the ESA resistance index with transferrin saturation rate (TSAT), vitamin D analogue dose, and sevelamer dose. In multivariate analysis, the sevelamer dose and TSAT were found to be independent determinants of the ESA resistance index. Our preliminary data showed an independent association between sevelamer dose and the responsiveness to ESA in haemodialysis patients. Further studies are required to investigate the causal relationship between sevelamer and ESA responsiveness.

Eficacia del cinacalcet en el hiperparatiroidismo secundario en hemodiálisis: análisis de los factores que influyen en su respuesta

Background Several authors have shown the difficulty of achieving the targets established in published guidelines for the treatment of secondary hyperparathyroidism. Cinacalcet can reduce serum parathyroid hormone (PTHi) levels, thus helping to achieve established targets. The aim of the present study was to analyze how cinacalcet can facilitate control of secondary hyperparathyroidism by comparing our results with the target levels recommended in guidelines and to identify the factors that could influence response to this drug. Material and methods We retrospectively collected information on the response of 74 hemodialysis patients with secondary hyperparathyroidism (baseline PTHi levels >300 pg/ml) who were treated with cinacalcet for at least 6 months. We recorded serum calcium (Ca), phosphorus (P), and PTHi levels at 3, 6, 9 months and at the end of follow-up. The baseline and final doses of phosphorus captors were also recorded. Results At the end of the follow-up, cinacalcet reduced serum levels of PTHi by 36%, P by 13.2%, Ca by 6%, and calcium-phosphorus product (CaxP) by 12.9%. At the start of treatment, P was >5.5 mg/dl in 38.4% of the patients, Ca was <8.4 mg/dl in 2.7%, and CaxP was >55 mg 2/dl 2 in 37.8%. After cinacalcet treatment, 50% of patients had PTHi <300 pg/ml, the percentage of patients with P >5.5 mg/dl was reduced to 24.7%, the prevalence of hypocalcemia increased to 12.2%, and the percentage of patients with CaxP>55 mg 2/dl 2 was reduced to 14.9%. The presence of hypocalcemia was independent of baseline PTHi levels and the degree of control of hyperparathyroidism reached after cinacalcet treatment. Most patients were managed without vitamin D (paricalcitol), which was discontinued in 24.3% who received this drug before cinacalcet therapy and was added to treatment in only 13.5% of patients with inadequate control of PTHi. After cinacalcet treatment, calcium carbonate doses increased (baseline 1.5±3.8 g/day vs final 2.4±4.9 g/day; p=0.03) with a non-significant reduction in sevelamer doses. When we analyzed the degree of final response to cinacalcet, we observed that levels of PTHi at 3 months were significantly lower in patients who reached PTHi <300 pg/ml at the end of follow-up, with lower final doses of cinacalcet (78% of patients with doses of 30 mg/day or less). When we reviewed the effect of phosphorus captors, we found that patients with higher doses of sevelamer at baseline showed a worse response, required higher cinacalcet doses, and less frequently achieved target PTHi levels. Multiple regression analysis confirmed that the degree of response depended on baseline PTHi levels and baseline sevelamer doses. Conclusions Cinacalcet facilitates control of secondary hyperparathyroidism. The PTH levels reached after 3 months of cinacalcet treatment have a prognostic value in predicting final response. The degree of response depends on the severity of secondary hyperparathyroidism, reflected by baseline PTHi levels and the sevelamer doses prescribed.

Does Concomitant Administration of Sevelamer and Calcium Carbonate Modify the Control of Phosphatemia?

There is no guideline regarding the concomitant or distant administration of sevelamer and calcium carbonate. Our aim was to determine whether serum phosphate varied when sevelamer and calcium carbonate were administered concomitantly in comparison to administration at separate meals. Fourteen chronic hemodialysis patients were enrolled in this cross-over, randomized trial. Each subject underwent two four-week study periods. During the "concomitant" period, subjects were instructed to take both sevelamer and calcium carbonate together at each meal, whereas in the "separate" period, they were required to take them at separate meals. The order of the "concomitant" and "separate" periods was randomized. Phosphate-binding agents were stopped for a one-week washout period before each study period. The total dose of sevelamer and calcium carbonate for each subject remained the same for the whole duration of the study and had been determined according to their usual dose of phosphate binders. Patients were instructed to keep their usual eating habits constant and a nutritionist evaluated the daily phosphate intake three times per week. Dialysis parameters were kept constant. Pre-dialysis serum phosphate, calcium, bicarbonate, and albumin were measured at the end of each week. The average daily dietary phosphate intake remained unchanged throughout the study. At the end of the two study periods there was no significant difference in serum phosphate (1.50 +/- 0.46 mmol/L in the "concomitant" period vs. 1.51 +/- 0.31 mmol/L in the "separate" period, P = 0.97), calcium (2.26 +/- 0.19 mmol/L in the "concomitant" period vs. 2.27 +/- 0.15 mmol/L in the "separate" period, P = 0.64), calcium x phosphate product (3.36 +/- 0.94 mmol(2)/L(2) in the "concomitant" period vs. 3.41 +/- 0.71 mmol(2)/L(2) in the "separate" period, P = 0.84) and bicarbonate levels (21.5 +/- 3.3 mmol/L for the "concomitant" period vs. 21.6 +/- 3.1 mmol/L for the "separate" period, P = 0.81). Our results show that simultaneous administration of calcium carbonate and sevelamer does not decrease phosphate-binding capacity. Hence, patients can choose to take their phosphate binders concomitantly or at separate meals, according to their preference.

Analysis of the efficacy and factors influencing the response of secondary hyperparathyroidism patients on hemodialysis to cinacalcet

Treatment of secondary hyperparathyroidism with cinacalcet improves control of PTH, phosphorus, calcium and Ca x P product, enabling to achieve targets recommended by K/DOQI guidelines for PTHi in only 30-50% of patients, in studies with a very selected population. The aim of this study was to analyze its effectiveness in real clinical practice, comparing results with targets recommended by K/DOQI and KDIGO guidelines and to investigate factors having influence on PTH responsiveness to cinacalcet. We collected data of evolution of 74 patients on hemodialysis with secondary hyperparathyroidism who were treated with cinacalcet for at least 6 months. According K/DOQI targets we observed a reduction of proportion of patients with PTHi > 300 pg/ml to 50%, a decrease of hyperphosphoremia from 38.4% to 23.3% and proportion of patients with Ca x P product > 55 mg2/dl2 from 37.8% to 15.1%. By contrast, presence of hypocalcemia increases from 2.7% to 12.3%. Comparing with KDIGO targets, proportion of patients with PTHi > 600 pg/ml decreased from 41.1% to 16.4% and with hyperphosphoremia from 68.5% to 52.1%. However, when considering patients with baseline PTHi > 600 pg/ml prevalence of P > 4.5 mg/dl decreased from 83.3% to 55.2%. We observed significant changes of phosphate binders after cinacalcet treatment with an increase in calcium carbonate doses (pre 0.61 +/- 1.53 g of calcium/day vs post-cinacalcet 0.95 +/- 1.98 g of calcium/day; p = 0.03) that was prescribed to prevent hypocalcemia and not as phosphate binder. Responsiveness were lower in patients who were taking higher doses of sevelamer at baseline, showing at the end of the study higher PTHi (no-sevelamer: 312 +/- 245 pg/ml; sevelamer < 6.4 g/day: 510 +/- 490 pg/ml; sevelamer > 6.4 g/day: 526 +/- 393 pg/ml; p = 0.04) and phosphorus (no-sevelamer: 4.5 +/- 1.2 mg/dl; sevelamer < 6.4 g/day: 4.2 +/- 1.5 mg/dl; sevelamer > 6.4 g/day: 5.7 +/- 0.9 mg/dl; p=0.01) serum levels. Use of paricalcitol did not show any influence on PTH response. Patients achieving targets for PTH at the end of the study showed a good response early, with a significant decrease of PTHi levels at three months (159 +/- 84 vs 630 +/- 377 pg/ml; p < 0.001) with significantly lower doses of cinacalcet (33.8 +/- 22.5 vs 51.1 +/- 25.1 mg/day; p = 0.003). Using multivariate analysis we found that percent of PTHi reduction was related with baseline PTHi levels and taking sevelamer as phosphate binder at baseline. Use of cinacalcet improves grade of control of secondary hyperparathyroidism in non-selected patients in hemodialysis, showing poor response in population with higher PTHi levels and who takes higher doses of sevelamer at baseline. By contrast, a reduction of PTHi levels at 3 months of treatment with relatively lower doses is a pronostic marker of good response to cinacalcet treatment.

Predictors of anemia in patients on hemodialysis

Even though the use of erythropoietin and intravenous iron has improved the treatment of anemia in hemodialysis patients, a considerable proportion of these patients still have anemia. The aim of this study was to identify predictors of anemia in a hemodialysis population. In a single-center hemodialysis unit, all patients were studied with blood tests and their medication recorded during a period of 22 months. Correlations with hemoglobin (Hb) were performed with a simple regression or a t test. Variables that reached 5% significance were entered in a multiple regression analysis. Selected variables were presented in quartiles with levels of Hb. Mean Hb was 11.3 g/dL, and 53 patients (40%) had Hb<11.0 g/dL. In the simple regression analysis Hb correlated positively with s-iron, CHr, s-albumin, and doses of sevelamer, and negatively with sedimentation rate (SR), ferritin, base excess, and doses of erythropoietin. In the multiple regression analysis erythrocytes SR was the only variable that remained significant. Elevated SR is the strongest predictor of anemia in hemodialysis patients receiving adequate treatment with erythropoietin and intravenous iron. Patients using high doses of sevelamer had higher Hb levels than patients using low doses.

Sevelamer hydrochloride: A novel treatment of hyperphosphatemia associated with tumor lysis syndrome in children

Sevelamer is a phosphate-binder used effectively for the treatment of hyperphosphatemia in patients treated with dialysis. To describe the safety of sevelamer in children with hyperphosphatemia secondary to tumor lysis syndrome and the serum phosphate concentrations observed following its administration. A retrospective chart review of all children with leukemia/lymphoma diagnosed between November 2002 and April 2004 who received sevelamer during their initial admission was conducted. We monitored the effects of sevelamer on serum phosphate concentration, calcium/phosphate product and renal function at hours 24, 48, and 72 from sevelamer initiation. Thirteen patients received sevelamer during the study period. Their median age was 13 years (range 2.7-17.9) and eight were boys. Nine children had acute lymphoblastic leukemia, one had acute myeloid leukemia and 3 had non-Hodgkin's lymphoma. The most frequently used dose of sevelamer was 400 mg orally twice daily. The median duration of sevelamer therapy was 2 days (range 1-7). Two children were excluded from the efficacy analysis due to concurrent use of dialysis. Mean serum phosphate levels decreased after sevelamer administration, in eleven patients, from a baseline 2.2 mmol/L +/- 0.4 (95% CI, 1.7-3.1) to 1.1 mmol/L +/- 0.2 at hour 72 (95%CI, 0.6-1.5). The only toxicity attributed to sevelamer was mild vomiting in three patients. Sevelamer appears to be effective and tolerable for the treatment of hyperphosphatemia associated with tumor lysis syndrome.