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Purpose It has been proved that the gut microbiome is altered in patients with chronic kidney disease. This contributes to chronic inflammation and increases cardiovascular risk and mortality, especially in those undergoing hemodialysis. Phosphate binders may potentially induce changes in their microbiome. This trial aimed to compare the changes in the gut microbiome of hemodialysis patients treated with calcium acetate to those treated with sucroferric oxyhydroxide. Methods Twelve hemodialysis patients were distributed to receive calcium acetate or sucroferric oxyhydroxide for 5 months. Blood samples (for biochemical analysis) and stool samples (for microbiome analysis) were collected at baseline, 4, 12, and 20 weeks after treatment initiation. Fecal DNA was extracted and a 16S rRNA sequencing library was constructed targeting the V3 and V4 hypervariable regions. Results Regarding clinical variables and laboratory parameters, no statistically significant differences were observed between calcium acetate or sucroferric oxyhydroxide groups. When analyzing stool samples, we found that all patients were different (p = 0.001) among themselves and these differences were kept along the 20 weeks of treatment. The clustering analysis in microbial profiles grouped the samples of the same patient independently of the treatment followed and the stage of the treatment. Conclusion These results suggest that a 5-month treatment with either calcium acetate or sucroferric oxyhydroxide did not modify baseline diversity or baseline bacterial composition in hemodialysis patients, also about the high-variability profiles of the gut microbiome found among these patients.

Bone cement from polymethylmethacrylate powder and methylmethacrylate liquid has been successfully demonstrated as artificial material to anchor joint replacements in bone. However, it lacks the capability to bond directly to bone, so long-term implantation leads to an increased risk of loosening. Bioactive materials show better performance in fixation to bone, and the chemical bonding depends on bone-like apatite formation. This is triggered by surface reactions with body fluid. For these reactions, superficial functional groups like silanol (Si–OH) are ideal sites to induce apatite nucleation and the release of Ca2+ ions accelerates the apatite growth. Therefore, incorporation of materials containing these key components may provide the cement with apatite-forming ability. In this study, phosphoric acid 2-hydroxyethyl methacrylate ester or bis[2-(methacryloyloxy)ethyl] phosphate supplying a phosphate group (PO4H2) was added into methylmethacrylate liquid, while calcium acetate as a source of Ca2+ ions was mixed into polymethylmethacrylate powder. The influences of the combinations on the setting time and compressive strength were also investigated. Apatite was formed on the cements modified with 30 mass% of phosphoric acid 2-hydroxyethyl methacrylate ester or bis[2-(methacryloyloxy)ethyl] phosphate. The induction period was shortened with increased amounts of Ca(CH3COO)2. The setting time could be controlled by the Ca(CH3COO)2/monomer mass ratio. Faster setting was achieved at a ratio close to the mixing ratio of the powder/liquid (2:1), and both increases and decreases in the amount of Ca(CH3COO)2 prolonged the setting time based on this ratio. The highest compressive strength was 88.8 ± 2.6 MPa, higher than the lowest limit of ISO 5833 but was lower than that of the simulated body fluid-soaked reference. The increase of additives caused the decline in compressive strength. In view of balancing apatite formation and clinical standard, bis[2-(methacryloyloxy)ethyl] phosphate is more suitable as an additive, and the optimal modification is a combination of 30 mass% of bis[2-(methacryloyloxy)ethyl] phosphate and 20 mass% of Ca(CH3COO)2.

Background. Phosphate binders are required to control serum phosphorus in dialysis patients. A phosphate binder combining calcium and magnesium offers an interesting therapeutic option. Methods. This controlled randomized, investigator-masked, multicentre trial investigated the effect of calcium acetate/magnesium carbonate (CaMg) on serum phosphorus levels compared with sevelamer hydrochloride (HCl). The study aim was to show non-inferiority of CaMg in lowering serum phosphorus levels into Kidney Disease Outcome Quality Initiative (K/DOQI) target level range after 24 weeks. Three hundred and twenty-six patients from five European countries were included. After a phosphate binder washout period, 255 patients were randomized in a 1:1 fashion. Two hundred and four patients completed the study per protocol (CaMg, N = 105; dropouts N = 18; sevelamer-HCl, N = 99; dropouts N = 34). Patient baseline characteristics were similar in both groups. Results. Serum phosphorus levels had decreased significantly with both drugs at week 25, and the study hypothesis of CaMg not being inferior to sevelamer-HCl was confirmed. The area under the curve for serum phosphorus (P = 0.0042) and the number of visits above K/DOQI (≤1.78 mmol/L, P = 0.0198) and Kidney disease: Improving global outcomes (KDIGO) targets (≤1.45 mmol/L, P = 0.0067) were significantly lower with CaMg. Ionized serum calcium did not differ between groups; total serum calcium increased in the CaMg group (treatment difference 0.0477 mmol/L; P = 0.0032) but was not associated with a higher risk of hypercalcaemia. An asymptomatic increase in serum magnesium occurred in CaMg-treated patients (treatment difference 0.2597 mmol/L, P < 0.0001). There was no difference in the number of patients with adverse events. Conclusion. CaMg was non-inferior to the comparator at controlling serum phosphorus levels at Week 25. There was no change in ionized calcium; there was minimal increase in total serum calcium and a small increase in serum magnesium. It had a good tolerability profile and thus may represent an effective treatment of hyperphosphataemia.

The use of polymethylmethacrylate (PMMA)-based bone cement is popular in orthopedics for the fixation of artificial joints with bone. However, it has a major problem with prostheses loosening because of coverage by fibrous tissue after long-term implantation. Recently, a bioactive bone cement has been developed that shows direct bonding to living bone through modification of PMMA resin with γ-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. The cement is designed to exhibit bioactivity, through incorporation of silanol groups and calcium ions. Thus, it has the potential to form a layer of bone-like hydroxyapatite, which is essential for achieving direct bonding to living bone. This type of modification allows the cement to show spontaneous hydroxyapatite formation on its surface in a simulated body fluid after one day, and there is evidence of osteoconduction of the cement in rabbit tibia for periods of more than three weeks. However, the influence of the dissolved ions from the modified cement has not yet been clarified. Thus, the authors focused on the dissolution of the modified PMMA-based bone cement and its tissue response in muscle and bone by comparison with the behavior of non-modified PMMA-based bone cement. One week after implantation in the latissimus dorsi of a rabbit, the modified PMMA-based bone cement showed more inflammatory width than the commercial cement. However, four weeks after implantation, the inflammatory width of both cements was essentially the same. The osteoconductivity around the modified cement was higher than that for the conventional cement after four weeks implantation. These results indicate that the initial dissolution of calcium acetate from the modified cement to form the hydroxyapatite induced the acute inflammation around tissue, but also developed the osteoconductivity. It is suggested that the initial inflammation can be effective for inducing osteoconduction through a bone healing reaction when the material provides an environment that promotes bone formation.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis. Hyperphosphatemia in patients with ESRD leads to secondary hyperparathyroidism, renal osteodystrophy, and is independently associated with mortality risk. The exact mechanism by which hyperphosphatemia increases mortality risk is unknown, but it may relate to enhanced cardiovascular calcification. National Kidney Foundation K/DOQI bone metabolism and disease guidelines recommend maintenance of serum phosphorus (P) below 5.5 mg/dL, and Ca x P product less than 55 mg(2)/dL(2). Although calcium-based phosphate binders (CBPB) are cost effective, long-term safety concerns relate to their postulated role in progression of cardiovascular calcification. Sevelamer hydrochloride has been recommended as an alternative noncalcium phosphate binder. Results from the Calcium Acetate Renagel Evaluation (CARE study) indicate that calcium acetate is more effective than sevelamer in controlling serum phosphorous and Ca x P product in hemodialysis patients. In the Treat-to-Goal study, dialysis patients treated with sevelamer had slower progression of coronary and aortic calcification than patients treated with CBPB. The mechanism underlying the beneficial effect of sevelamer is unknown, but may relate to decreased calcium loading or to dramatic reductions in LDL cholesterol in sevelamer-treated patients. At present, evidence incriminating CBPB in the progression of cardiovascular calcification in ESRD remains largely circumstantial. As calcium acetate is more efficacious and cost effective than sevelamer, it remains an accepted first-line phosphate binder. In this review, we will examine these issues and provide rational guidelines for the use of calcium-based phosphate binders in patients on maintenance hemodialysis.

Treatment of hyperphosphatemia in patients with chronic kidney disease on maintenance hemodialysis: Results of the CARE study. Most patients with end-stage renal disease develop hyperphosphatemia because their dietary intake exceeds phosphorus elimination by intermittent thrice-weekly dialysis. Inadequately treated hyperphosphatemia plays a central role in the pathogenesis of secondary hyperparathyroidism and extraosseous calcification. Moreover, in the last 15 years, this biochemical abnormality has become increasingly important following the publication of two epidemiologic studies that demonstrated an association between elevated serum phosphorus and increased mortality risk in patients with end-stage renal disease. As a result, the National Kidney Foundation Kidney Disease Outcome and Quality Initiative (K/DOQI) Bone Metabolism and Chronic Kidney Disease Guidelines recommend that serum phosphorus levels be maintained between 3.5 and 5.5 mg/dL. Unfortunately, cross-sectional studies have shown a mean serum phosphorus of 6.2 mg/dL in the maintenance hemodialysis population in the United States. An alarming 60% of patients have serum phosphorus in excess of the 5.5 mg/dL level recommended by K/DOQI guidelines. In order to achieve this new target for serum phosphorus, the most efficacious and cost-effective phosphate binders currently available should be utilized. In this review, we discuss the results of the Calcium Acetate Renagel Evaluation (CARE study), which clearly demonstrated the superiority of calcium acetate over sevelamer hydrochloride for controlling serum phosphorus and calcium-phosphate product to the levels recommended by the K/DOQI guidelines.

Keywords: bone markers, calcium acetate, fibroblast growthfactor-23, haemodialysis, magnesium carbonate, phosphatebinderABSTRACTBackground. Different phosphate binders exert differingeffects on bone mineral metabolism and levels of regulatinghormones. The objective of this post hoc evaluation of theCALcium acetate MAGnesium carbonate (CALMAG) studywas to compare the effects of calcium acetate/magnesium car-bonate (CaMg) and a calcium-free phosphate binder, sevela-mer-hydrochloride (HCl), on serum levels of fibroblast growthfactor-23 (FGF-23) and markers of bone turnover.Methods. This secondary analysis of the controlled, random-ized CALMAG study, comparing the effect of CaMg and seve-lamer-HCl on serum phosphorus (P), aimed to investigate theparameters described above. The analysis included 204patients who completed the initial study per protocol (CaMg,n=105; sevelamer-HCl, n=99).Results. ThestudyshowedthatserumlevelsofFGF-23weresig-nificantly reduced with CaMg and sevelamer-HCl, with nodifference between groups at Week 25 [analysis of covariance(ANCOVA); log-intact FGF-23 (iFGF-23), P=0.1573]. FGF-23levelsstronglycorrelatedwithserumPlevelsatalltimepointsinboth groups. The bone turnover parameters alkaline phospha-tase (AP), bone AP (BAP), procollagen type 1 amino-terminalpropeptide 1 (P1NP), osteoprotegerin (OPG), beta-crosslaps (β-CTX) and tartrate-resistant acid phosphatase 5b (TRAP 5b) in-creased significantly in the sevelamer-HCl group; they remainedalmostunchangedintheCaMggroup,aftertheinitialphaseofPlowering(ANCOVA,P

Treatment of hyperphosphatemia in hemodialysis patients: The Calcium Acetate Renagel Evaluation (CARE Study).BackgroundHyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients.MethodsTo determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus ≤5.5mg/dL and Ca × P product ≤55mg2/dL2, we conducted an 8-week randomized, double-blind study in 100 hemodialysis patients.ResultsComparisons of time-averaged concentrations (weeks 1 to 8) demonstrated that calcium acetate recipients had lower serum phosphorus (1.08mg/dL difference, P = 0.0006), higher serum calcium (0.63mg/dL difference, P < 0.0001), and lower Ca × P (6.1mg2/dL2 difference, P = 0.022) than sevelamer recipients. At each week, calcium acetate recipients were 20% to 24% more likely to attain goal phosphorus [odds ratio (OR) 2.37, 95% CI 1.28–4.37, P = 0.0058], and 15% to 20% more likely to attain goal Ca × P (OR 2.16, 95% CI 1.20–3.86, P = 0.0097). Transient hypercalcemia occurred in 8 of 48 (16.7%) calcium acetate recipients, all of whom received concomitant intravenous vitamin D. By regression analysis hypercalcemia was more likely with calcium acetate (OR 6.1, 95% CI 2.8–13.3, P < 0.0001). Week 8 intact PTH levels were not significantly different. Serum bicarbonate levels were significantly lower with sevelamer hydrochloride treatment (P < 0.0001).ConclusionCalcium acetate controls serum phosphorus and calcium-phosphate product more effectively than sevelamer hydrochloride. Cost-benefit analysis indicates that in the absence of hypercalcemia, calcium acetate should remain the treatment of choice for hyperphosphatemia in hemodialysis patients.