Poly[allylamine hydrochloride] (RenaGel): a noncalcemic phosphate binder for the treatment of hyperphosphatemia in chronic renal failure. Lanthanum carbonate reduces phosphorus burden in patients with CKD stages 3 and 4: a randomized trial. A comparison of the calcium-free phosphate binder sevelamer hydrochloride with calcium acetate in the treatment of hyperphosphatemia in hemodialysis patients. A randomized, double-blind, placebo-controlled trial of niacinamide for reduction of phosphorus in hemodialysis patients. Effect of MCI-196 (colestilan) as a phosphate binder on hyperphosphataemia in aemodialysis patients: a double-blind, placebo-controlled, short-term trial. Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients. Effects of sevelamer and calcium-based phosphate binders on mortality in hemodialysis patients. Multicenter prospective randomized, double-blind comparative study between lanthanum carbonate and calcium carbonate as phosphate binders in Japanese hemodialysis patients with hyperphosphatemia. Suppression of secondary hyperparathyroidism in children with chronic renal failure by high dose phosphate binders: calcium carbonate versus aluminium hydroxide. Randomized, double-blind, placebo-controlled, dose-titration, phase III study assessing the efficacy and tolerability of lanthanum carbonate: a new phosphate binder for the treatment of hyperphosphatemia. Calcium acetate versus calcium carbonate as phosphate-binding agents in chronic haemodialysis. Calcium acetate versus calcium carbonate as phosphorus binders in patients on chronic haemodialysis: a controlled study. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end-stage renal disease. A randomized crossover trial comparing sevelamer with calcium acetate in children with CKD. Iron-magnesium hydroxycarbonate (fermagate): a novel non-calcium-containing phosphate binder for the treatment of hyperphosphatemia in chronic hemodialysis patients. Treatment of hyperphosphatemia with sevelamer hydrochloride in hemodialysis patients: a comparison with calcium acetate. Efficacy and safety of sevelamer hydrochloride and calcium acetate in patients on peritoneal dialysis. Efficacy and safety of lanthanum carbonate for reduction of serum phosphorus in patients with chronic renal failure receiving hemodialysis. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Efficacy and safety of sevelamer. Comparison with calcium carbonate in the treatment of hyperphosphatemia in hemodialysis patients. Magnesium carbonate is an effective phosphate binder for chronic hemodialysis patients: a pilot study. Phosphate-binding effects of sucralfate in patients with chronic renal failure. Phosphate binder impact on bone remodeling and coronary calcification--results from the BRiC study. Improvements in renal osteodystrophy in patients treated with lanthanum carbonate for two years. [A comparison of phosphorus-chelating effect of calcium carbonate versus calcium acetate before dialysis]. Results of a randomized crossover study comparing once-daily and thrice-daily sevelamer dosing. Randomized prospective study of a nonthiazide diuretic, indapamide, in preventing calcium stone recurrences. Magnesium carbonate for phosphate control in patients on hemodialysis. A randomized controlled trial. A randomized double-blind placebo-controlled trial of cyclosporine in steroid-resistant idiopathic focal segmental glomerulosclerosis in children. Comparison of calcium acetate with calcium carbonate as phosphate binder in patients on maintenance haemodialysis. An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate. Comparison of sevelamer hydrochloride with colestimide, administered alone or in combination with calcium carbonate, in patients on hemodialysis. Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients. Calcium ketoglutarate versus calcium acetate for treatment of hyperphosphataemia in patients on maintenance haemodialysis: a cross-over study. Higher strength lanthanum carbonate provides serum phosphorus control with a low tablet burden and is preferred by patients and physicians: a multicenter study. Comparison of calcium carbonate and aluminium hydroxide as phosphate binders on biochemical bone markers, PTH(1-84), and bone mineral content in dialysis patients. Calcium acetate versus calcium carbonate for the control of serum phosphorus in hemodialysis patients. Efficacy, tolerability, and safety of lanthanum carbonate in hyperphosphatemia: a 6-month, randomized, comparative trial versus calcium carbonate. More dietetic time, better outcome? A randomized prospective study investigating the effect of more dietetic time on phosphate control in end-stage kidney failure haemodialysis patients. Randomized crossover study comparing the phosphate-binding efficacy of calcium ketoglutarate versus calcium carbonate in patients on chronic hemodialysis. The effects of lipid-lowering agents on acute renal allograft rejection. Effects of a supplemented hypoproteic diet in chronic kidney disease. Physiological effects of slow release potassium phosphate for absorptive hypercalciuria: a randomized double-blind trial. Controlled trial of 1apha-hydroxycholecalciferol in chronic renal failure. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Calcium carbonate as a phosphate binder in dialysis patients: evaluation of an enteric-coated preparation and effect of additional aluminium hydroxide on hyperaluminaemia. Lanthanum carbonate vs. sevelamer hydrochloride for the reduction of serum phosphorus in hemodialysis patients: a crossover study. Calcium acetate versus calcium carbonate in the control of hyperphosphatemia in hemodialysis patients. Aluminum hydroxide, calcium carbonate and calcium acetate in chronic intermittent hemodialysis patients. Lanthanum carbonate (Fosrenol) efficacy and tolerability in the treatment of hyperphosphatemic patients with end-stage renal disease. Doxercalciferol safely suppresses PTH levels in patients with secondary hyperparathyroidism associated with chronic kidney disease stages 3 and 4. Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients.
Dietary phosphate restriction and the oral administration of calcium and aluminum salts have been the principal means of controlling hyperphosphatemia in individuals with end-stage renal disease over the past decade. Although relatively well-tolerated, a large fraction of patients treated with calcium develop hypercalcemia, particularly when administered concurrently with calcitriol, despite a lowering of the dialysate calcium concentration. We evaluated the efficacy of cross-linked poly[allylamine hydrochloride] (RenaGel; Geltex Pharmaceuticals, Waltham, MA), a nonabsorbable calcium- and aluminum-free phosphate binder, in a randomized, placebo-controlled, double-blind trial of 36 maintenance hemodialysis patients followed over an 8-week period. RenaGel was found to be as effective as calcium carbonate or acetate as a phosphate binder. The reduction in serum phosphorus was significantly greater after 2 weeks of treatment with RenaGel (6.6 +/- 2.1 mg/dL to 5.4 +/- 1.5 mg/dL) compared with placebo (7.0 +/- 2.1 mg/dL to 7.2 +/- 2.4 mg/dL; P = 0.037). There was no significant change in serum calcium concentration in either treatment group. The total serum cholesterol and low-density lipoprotein cholesterol fraction were significantly reduced in RenaGel-treated patients compared with placebo-treated patients (P = 0.013 and P = 0.003, respectively) without a concomitant reduction in high-density lipoprotein cholesterol (P = 0.93). There was no difference among recipients of RenaGel and placebo in terms of adverse events. RenaGel is a safe and effective alternative to oral calcium for the management of hyperphosphatemia in end-stage renal disease. Lanthanum carbonate (FOSRENOL, Shire Pharmaceuticals) is an effective noncalcium, nonresin phosphate binder for the control of hyperphosphatemia in chronic kidney disease (CKD) stage 5 patients undergoing dialysis.
                A Phase 2, randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of lanthanum carbonate in CKD stage 3 and 4 patients. Of 281 patients screened, 121 were randomized (2:1) to lanthanum carbonate or placebo (80 versus 41). The modified intent-to-treat population included 90 patients (56 versus 34); 71 (43 versus 28) completed the study. After run-in, when any current phosphate binders were discontinued and dietary counseling reinforced, patients with serum phosphorus >4.6 mg/dl received lanthanum carbonate (titrated up to 3000 mg/d) or matching placebo for 8 wk.
                At the end of treatment, 25 (44.6%) versus nine (26.5%) patients had serum phosphorus < or =4.6 mg/dl (difference 18.1%, P = 0.12) in the lanthanum carbonate and placebo groups, respectively. Statistically significant differences were observed between groups in change from baseline to end of treatment for serum phosphorus (P = 0.02), intact parathyroid hormone (P = 0.02), and urinary phosphorus excretion (P = 0.04). The safety profile and tolerability of lanthanum carbonate were similar to that of placebo.
                Because <1% of phosphorus is in the extracellular fluid, serum measurements may not accurately reflect total body burden in patients with CKD stages 3 and 4. However, lanthanum carbonate is an effective phosphate binder in this patient population, with a safety profile and tolerability similar to that of placebo. Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia and aluminum-based binders that result in total body aluminum accumulation over time. This investigation describes the use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis patients and compares it with a standard calcium-based phosphate binder. An open-label, randomized, crossover study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were administered either sevelamer or calcium acetate, and the dosages were titrated upward to achieve improved phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Eighty-four patients from eight centers participated in the study. There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-2.0 +/- 2.3 mg/dL) and calcium acetate (-2.1 +/- 1.9 mg/dL). Twenty-two percent of patients developed a serum calcium greater than 11.0 mg/dL while receiving calcium acetate, versus 5% of patients receiving sevelamer (P < 0.01). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 24% mean decrease in serum low-density lipoprotein cholesterol levels. Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium acetate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients. Niacinamide inhibits intestinal sodium/phosphorus transporters and reduces serum phosphorus in open-label studies. A prospective, randomized, double-blind, placebo-controlled crossover trial was performed for assessment of the safety and efficacy of niacinamide.
                Hemodialysis patients with phosphorus levels > or =5.0 mg/dl were randomly assigned to 8 wk of niacinamide or placebo, titrated from 500 to 1500 mg/d. After a 2-wk washout period, patients switched to 8 wk of the alternative therapy. Vitamin D analogs and calcimimetics were held constant; phosphorus binders were not changed unless safety criteria were met.
                Thirty-three patients successfully completed the trial. Serum phosphorus fell significantly from 6.26 to 5.47 mg/dl with niacinamide but not with placebo (5.85 to 5.98 mg/dl). A concurrent fall in calcium-phosphorus product was seen with niacinamide, whereas serum calcium, intact parathyroid hormone, uric acid, platelet, triglyceride, LDL, and total cholesterol levels remained stable in both arms. Serum HDL levels rose with niacinamide (50 to 61 mg/dl but not with placebo. Adverse effects were similar between both groups. Among patients who were > or =80% compliant, results were similar, although the decrease in serum phosphorus with niacinamide was more pronounced (6.45 to 5.28 mg/dl) and the increase in HDL approached significance (49 to 58 mg/dl).
                In hemodialysis patients, niacinamide effectively reduces serum phosphorus when co-administered with binders and results in a potentially advantageous increase in HDL cholesterol. Further study in larger randomized trials and other chronic kidney disease populations is indicated. MCI-196 (colestilan), an anion exchange resin, is widely used as an anti-hypercholesterolaemic drug in Japan. To evaluate the efficacy and safety of MCI-196 as a phosphate binder, a double-blind, randomized, placebo-controlled prospective trial was conducted in Japanese end-stage renal disease patients with hyperphosphataemia on intermittent haemodialysis treatment.
                Phosphate binders were discontinued during a 2-week washout period. Subsequently, patients whose serum phosphorus levels were > or =6.5 mg/dl, but <10 mg/dl were eligible to enter the treatment protocol. Patients were randomized to either MCI-196 6 g/day or placebo for 2 weeks. The efficacy and safety of MCI-196 were assessed in 33 and 46 patients, respectively.
                Serum phosphorus in the placebo group increased by 0.84+/-0.95 mg/dl (mean+/-SD), while serum phosphorus in the MCI-196 group decreased by 0.55+/-1.23 mg/dl. The difference between the two groups was statistically significant (P = 0.002). A reduction of > or =1 mg/dl in serum phosphorus was observed in 43% in the MCI-196 group and 0% of patients in the placebo group (P = 0.0122). Calcium-phosphorus (Ca x P) product, intact parathyroid hormone (iPTH) and low-density lipoprotein (LDL)-cholesterol in the MCI-196 group also decreased significantly compared with the placebo group, while serum calcium was unchanged. Adverse reactions were observed in 51.7% of the MCI-196 group and 29.4% of the placebo group (P = 0.2186). The most frequent adverse reactions in the MCI-196 group were gastrointestinal symptoms and signs, including constipation.
                The present findings suggest that the short-term administration of MCI-196 is effective in decreasing serum phosphorus in haemodialysis patients. Its long-term efficacy needs to be evaluated. The risk of death in hemodialysis patients treated with calcium-containing phosphate binders or sevelamer is not known. We assessed all-cause mortality in 127 patients new to hemodialysis assigned to calcium-containing binders or sevelamer after a median follow-up of 44 months from randomization. This was a predetermined secondary end point of a randomized clinical trial designed to assess progression of coronary artery calcium (CAC) scores in the two treatment arms. Thirty-four deaths occurred during the follow-up period: 23 in subjects randomized to calcium-containing phosphate binders and 11 in subjects randomized to sevelamer. Baseline CAC score was a significant predictor of mortality after adjustment for age, race, gender, and diabetes with increased mortality proportional to baseline score (P=0.002). Mortality was borderline significantly lower in subjects randomized to sevelamer (5.3/100 patient years, confidence interval (CI) (2.2-8.5) compared to those randomized to calcium-containing binders (10.6/100 patient years, CI 6.3-14.9) (P=0.05). The greater risk of death for patients treated with calcium-containing phosphate binders persisted after full multivariable adjustment (P=0.016, hazard ratio 3.1, CI 1.23-7.61). In subjects new to hemodialysis baseline CAC score was a significant predictor of all-cause mortality. Treatment with sevelamer was associated with a significant survival benefit as compared to the use of calcium-containing phosphate binders. Elevated serum phosphorus and calcium are associated with arterial calcification and mortality in dialysis patients. Unlike calcium-based binders, sevelamer attenuates arterial calcification but it is unknown whether sevelamer affects mortality or morbidity. In a multicenter, randomized, open-label, parallel design trial we compared sevelamer and calcium-based binders on all-cause and cause-specific mortality (cardiovascular, infection, and other) in prevalent hemodialysis patients. A total of 2103 patients were initially randomized to treatment and 1068 patients completed the study. All-cause mortality rates and cause-specific mortality rates were not significantly different. There was a significant age interaction on the treatment effect. Only in patients over 65 years of age was there a significant effect of sevelamer in lowering the mortality rate. There was a suggestion that sevelamer was associated with lower overall, but not cardiovascular-linked, mortality in older patients. We suggest that further research is needed to confirm these findings. The efficacy of lanthanum carbonate as a phosphate binder for the treatment of hyperphosphatemia has been reported, but not from a double-blind, comparator-controlled comparative study.
                The safety and efficacy of lanthanum carbonate and calcium carbonate on serum phosphate and calcium levels in Japanese hemodialysis patients were assessed by a randomized, double-blind, comparator-controlled, parallel group, multicenter study. This study is the first study using a randomized, double-blind method to compare lanthanum carbonate and calcium carbonate as phosphate binders.
                In the double-blind phase, the changes in the serum phosphate level were similar in the lanthanum carbonate and calcium carbonate groups. The differences in the corrected serum calcium level or the calcium x phosphate products between the 2 groups were not statistically significant. However, the mean change in the corrected serum calcium level from baseline to the last outpatient visit was significantly lower in the lanthanum carbonate group than in the calcium carbonate group. The incidence of hypercalcemia in the lanthanum carbonate group was also significantly lower than in the calcium carbonate group.
                Both compounds show similar efficacy on the serum phosphate level in patients undergoing hemodialysis when the dose is managed in a dose-variable and double-blind manner. However, lanthanum carbonate is superior in terms of lowering the incidence of hypercalcemia. Secondary hyperparathyroidism was suppressed over a period of one year in 12 children with chronic renal failure by using a regimen of mild dietary phosphate restriction and high dose phosphate binders. The patients were randomised to receive either aluminium hydroxide or calcium carbonate by mouth for six months and then crossed over to the other medication. Vitamin D (dihydrotachysterol) dosage was unchanged. Serum parathyroid hormone concentrations were reduced to within the normal range, urinary cyclic adenosine monophosphate values fell, plasma phosphate concentrations decreased, and the theoretical renal phosphate threshold increased significantly. Transiliac bone biopsy findings improved in four patients with adequate suppression of parathyroid hormone concentrations, deteriorated in two patients who were not compliant, and did not change in five patients in whom initial bone disease was mild. Growth velocity improved significantly. There was no difference in the clinical response, biochemical changes, or incidence of complications during treatment with the two agents. In view of the risk of aluminium toxicity the use of high dose calcium carbonate with dietary phosphate restriction and vitamin D supplementation is recommended in the control of secondary hyperparathyroidism in children with chronic renal failure. Lanthanum carbonate is a novel, non-calcium, non-aluminum phosphate binder under evaluation for the treatment of hyperphosphatemia in end-stage renal disease (ESRD) patients receiving either hemodialysis or continuous ambulatory peritoneal dialysis.
                This 16-week study assessed the control of serum phosphorus with lanthanum carbonate, and its effects on serum calcium, calcium x phosphorus product, and parathyroid hormone (PTH). Hemodialysis patients > or =18 years old entered into a 1- to 3-week washout period during which serum phosphorus levels rose to >5.9 mg/dL (1.90 mmol/L). In total, 126 patients were titrated with lanthanum carbonate at doses containing 375, 750, 1,500, 2,250, or 3,000 mg/d elemental lanthanum, given in divided doses with meals over a 6-week period, to achieve serum levels < or =5.9 mg/dL. By the end of dose titration, 11/126 (9%) patients received < or =750 mg/d of lanthanum, 25 (20%) received 1,500 mg/d, 37 (29%) received 2,250 mg/d, and 53 (42%) received 3,000 mg/d. Following titration, patients were randomized to receive either lanthanum carbonate or placebo during a 4-week, double-blind maintenance phase.
                At the study endpoint, the mean difference in serum phosphorus between the lanthanum carbonate and placebo treatment arms was 1.91 mg/dL (0.62 mmol/L) (P < 0.0001). Calcium x phosphorus product (P < 0.0001) and serum PTH levels (P < 0.01) were also significantly lower with lanthanum carbonate versus placebo. The incidence of drug-related adverse events was similar between placebo- and lanthanum carbonate-treated patients.
                Lanthanum carbonate is an effective and well-tolerated agent for the treatment of hyperphosphatemia in patients with ESRD. Hyperphosphataemia plays a key role in the pathogenesis of renal osteodystrophy, and phosphate-binding agents are required in many chronic dialysis patients. Aluminium hydroxide and calcium carbonate are well-established phosphate binders, but their use is associated with toxicity or poor efficacy. Calcium acetate is known to be a potent phosphate binder, and has recently been used successfully in chronic dialysis patients. In this randomized cross-over trial in 31 chronic haemodialysis patients, equimolar doses of calcium acetate and calcium carbonate were administered for 6 weeks each. Compliance was estimated from tablet counts, and biochemical parameters were measured at the end of each treatment period. Of the 31 patients 23 completed both treatment arms; of the remainder, three withdrew due to adverse symptoms, hypercalcaemia necessitated treatment withdrawal in two, and three died. Non-compliance was significantly higher with acetate (18.3% tablets not taken) than with carbonate (8.7%). Serum phosphate was significantly lower after treatment with acetate (1.51 mmol/l) than with carbonate (1.80), as was the Ca x PO4 product (3.59 vs 4.18 respectively) and PTH (17.8 vs 25.4 pmol/l respectively). Serum calcium was significantly higher after acetate therapy (2.40 vs 2.32 mmol/l). No significant difference was found for sodium, potassium, bicarbonate, urea, creatinine, and haemoglobin. This study confirms that the treatment of hyperphosphataemia is more effective with calcium acetate than with calcium carbonate. For the first time an associated beneficial effect on secondary hyperparathyroidism has also been demonstrated. Patient tolerability of calcium acetate was considerably poorer, probably due in part to tablet formulation and bulkiness, as well as possible direct gastrointestinal effects of the acetate salt. The first reported double-blind cross-over comparison between the phosphorus binders calcium carbonate and calcium acetate was undertaken in 15 stable patients on chronic maintenance haemodialysis. Detailed registration of diet and analysis of the protein catabolic rate suggested an unchanged phosphorus intake during the study. It was found that predialytic serum phosphate concentration was significantly decreased by 0.11 mmol/l (0.34 mg/dl) (P = 0.021, 95% confidence limits 0.02-0.21 mmol/l; 0.06-0.65 mg/dl) during calcium acetate treatment. The calcium phosphate product was insignificantly decreased during treatment with calcium acetate whereas we could not exclude the possibility that calcium concentration had increased. Current treatment of secondary hyperparathyroidism in chronic kidney failure with calcium and active vitamin D is potentially limited by hypercalcemia and hyperphosphatemia. AMG 073 represents a new class of compounds for the treatment of hyperparathyroidism known as calcimimetics, which reduce parathyroid hormone (PTH) synthesis and secretion by increasing the sensitivity of the parathyroid calcium-sensing receptor (CaR) to extracellular calcium. The current study evaluates the efficacy and safety of AMG 073 when added to conventional treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD). Seventy-one hemodialysis patients with uncontrolled secondary hyperparathyroidism, despite standard therapy with calcium, phosphate binders, and active vitamin D sterols, were treated in this 18-wk, dose-titration study with single daily oral doses of AMG 073/placebo up to 100 mg. Changes in plasma PTH, serum calcium, serum phosphorus, and calcium x phosphorus levels were compared between AMG 073 and placebo groups. Mean PTH decreased by 33% in the AMG 073 patients compared with an increase of 3% in placebo patients (P = 0.001). A significantly greater proportion of AMG 073 patients (44%) had a mean PTH < or = 250 pg/ml compared with placebo patients (20%; P = 0.029). Also, a significantly greater proportion of AMG 073 patients (53%) had a decrease in PTH > or =30% compared with placebo patients (23%; P = 0.009). Calcium x phosphorus levels decreased by 7.9% in AMG 073 patients compared with an increase of 11.3% in placebo patients (P = 0.013). Adverse event rates were low and mostly mild to moderate in severity; however, the incidence of vomiting was higher in AMG 073 patients. In this study, the calcimimetic AMG 073 at doses up to 100 mg for 18 wk provided a safe and effective means to attain significant reductions in PTH and calcium x phosphorus levels in ESRD patients. AMG 073 represents a novel and promising therapy to improve the management of secondary hyperparathyroidism. A multicenter, randomized, open-label, crossover study was performed to compare the efficacy and safety of sevelamer, a calcium-free phosphate binder, with calcium acetate in pediatric patients with chronic kidney disease (CKD).
                Children (age, 0.9 to 18 years) with CKD undergoing hemodialysis or peritoneal dialysis or with a glomerular filtration rate of 20 or greater and less than 60 mL/min/1.73 m2 (> or = 0.33 and < 1.00 mL/s/1.73 m2) were randomly assigned to the following treatment scheme: 2 weeks of washout followed by 8 weeks of treatment with either sevelamer or calcium acetate in a crossover fashion. Phosphorus, calcium, and intact parathyroid hormone in serum were measured every 2 weeks, and phosphate binder dosages were adjusted, if needed. Serum lipid and vitamin concentrations were measured at the beginning and end of each treatment period. The primary end point was the decrease in serum phosphorus levels after 8 weeks of treatment.
                Forty-four patients were screened. Altogether, data for 18 patients (5 girls) aged 12.4 +/- 4.1 years were used for the crossover analysis. There was no significant difference in serum phosphorus levels at 8 weeks after the start of treatment in both groups. Total cholesterol (-27%) and low-density lipoprotein cholesterol (-34%) levels decreased significantly with sevelamer treatment (P < 0.02 and P < 0.005). An increased incidence of hypercalcemia (P < 0.0005) was observed with calcium acetate treatment, whereas metabolic acidosis was more frequent with sevelamer treatment (P < 0.005).
                Treatment of children with CKD with sevelamer and calcium acetate provides similar phosphorus level control. The marked decrease in lipid levels and lower rate of hypercalcemia may augment the long-term benefit of sevelamer. This phase II study tested the safety and efficacy of fermagate, a calcium-free iron and magnesium hydroxycarbonate binder, for treating hyperphosphatemia in hemodialysis patients.
                A randomized, double-blind, three-arm, parallel-group study compared two doses of fermagate (1 g three times daily or 2 g three times daily with placebo). Sixty-three patients who had been on a stable hemodialysis regimen for > or =3 mo were randomized to the treatment phase. Study medication was administered three times daily just before meals for 21 d. The primary endpoint was reduction in serum phosphate over this period.
                In the intention-to-treat analysis, mean baseline serum phosphate was 2.16 mmol/L. The fermagate 1- and 2-g three-times-daily treatment arms were associated with statistical reductions in mean serum phosphate to 1.71 and 1.47 mmol/L, respectively. Adverse event (AE) incidence in the 1-g fermagate arm was statistically comparable to the placebo group. The 2-g arm was associated with a statistically higher number of patients reporting AEs than the 1-g arm, particularly gastrointestinal AEs, as well as a higher number of discontinuations, complicating interpretation of this dose's efficacy. Both doses were associated with elevations of prehemodialysis serum magnesium levels.
                The efficacy and tolerability of fermagate were dose dependent. Fermagate showed promising efficacy in the treatment of hyperphosphatemia in chronic hemodialysis patients as compared with placebo in this initial phase II study. The optimal balance between efficacy and tolerability needs to be determined from future dose-titration studies, or fixed-dose comparisons of more doses. Sevelamer hydrochloride is a recently approved calcium- and aluminium-free phosphate binder. A randomized study comparing sevelamer and calcium acetate was performed to assess the control of hyperphosphatemia in hemodialysis patients.
                Administration of phosphate binders was discontinued during a two-week washout period. The patients were then randomized to receive sevelamer or calcium acetate. The laboratory tests were performed monthly for 34 weeks.
                There was a statistically significant decrease of serum phosphorus in both sevelamer and calcium acetate treatments. In addition, sevelamer improved the lipid profile.
                This study confirms that sevelamer is effective at lowering serum phosphorus in hemodialysis patients and that it has several striking properties that could be beneficial in atherosclerosis in dialysis patients. Inadequate phosphorus control is associated with increased morbidity and mortality in patients with CKD stage 5. Although phosphate binders are often used in patients on peritoneal dialysis (PD), no large randomized controlled studies evaluating their use solely in this population have previously been reported.
                In this multicentre, open-label study, adult patients on PD with serum phosphorus >5.5 mg/dl were randomized (2:1) to 12 weeks of treatment with sevelamer hydrochloride or calcium acetate. Doses were titrated to achieve serum phosphorus of 3.0-5.5 mg/dl. Changes in serum phosphorus, calcium, intact parathyroid hormone (iPTH), lipids and plasma biomarkers were assessed.
                A total of 253 patients were screened, 143 of whom were randomized (sevelamer hydrochloride, n = 97; calcium acetate, n = 46). Treatment groups were well balanced with regard to baseline demographics. Serum phosphorus levels were significantly reduced after 12 weeks with both sevelamer hydrochloride and calcium acetate (P < 0.001). Serum PTH was also reduced in both groups while serum calcium increased in the calcium acetate group (P = 0.001) but not in the sevelamer hydrochloride group. Sevelamer hydrochloride was also associated with decreases in total cholesterol, low-density lipoprotein cholesterol and uric acid and an increase in bone-specific alkaline phosphatase (all P < 0.001 versus baseline). Both treatments were well tolerated and safety profiles were consistent with previous reports in haemodialysis patients. Hypercalcaemia was experienced by more calcium acetate-treated patients (18 versus 2%; P = 0.001).
                In summary, sevelamer hydrochloride provides a reduction in serum phosphorus compared to that obtained with calcium-based binders in PD patients. The effects of sevelamer hydrochloride appear similar in both PD and haemodialysis populations. Lanthanum carbonate is a highly effective phosphate binder with significant potential as a treatment for hyperphosphatemia in patients with end-stage renal disease (ESRD). Here, the results of a placebo-controlled, dose-ranging study are presented.
                196 patients (> or = 18 years) receiving hemodialysis for at least 6 months entered a 1- to 3-week, single-blind, placebo run-in phase. Of these, 145 patients were randomized to a double-blind phase in which they received placebo or lanthanum carbonate in daily lanthanum doses of 225, 675, 1,350 or 2,250 mg for 6 weeks. Serum levels of phosphorus, calcium and parathyroid hormone, and adverse events were monitored throughout the study.
                The intent-to-treat analysis (n = 144) showed significant dose-related reductions in serum phosphorus at lanthanum doses of 675, 1,350 and 2,250 mg. After 6 weeks of treatment, phosphorus levels were significantly lower in the lanthanum groups receiving 1,350 mg/day and 2,250 mg/day, compared with the placebo group (respective changes from randomization: -0.95 +/- 1.39 mg/dl (-0.31 +/- 0.45 mmol/l), -1.13 +/- 2.01 mg/dl (-0.36 +/- 0.65 mmol/l), 0.75 +/- 1.47 mg/dl (0.24 +/- 0.47 mmol/l), p < 0.001). Significant reductions in serum phosphorus, compared with placebo, occurred in the lanthanum 1,350 mg/day group from the second week of treatment and in the 2,250 mg/day group from the first week of treatment. Adverse events were mainly gastrointestinal (e.g. nausea and vomiting). Treatment-related adverse events occurred in 39% of patients treated with lanthanum carbonate and 44% of the placebo group.
                Lanthanum carbonate is an effective and well-tolerated agent for the short-term treatment of hyperphosphatemia in patients with ESRD. A need exists for a therapy that lowers parathyroid hormone (PTH) without increasing calcium x phosphorus in patients with secondary hyperparathyroidism. The calcimimetic AMG 073 increases the sensitivity of the parathyroid calcium-sensing receptor to extracellular calcium, thereby reducing PTH secretion. Consequently, AMG 073 may provide a novel therapy for secondary hyperparathyroidism.
                Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week, double-blind, randomized, placebo-controlled, dose titration study. Daily oral AMG 073 doses were administered to determine the effect on PTH, serum calcium, phosphorus, and calcium x phosphorus.
                The mean baseline PTH was similar in patients administered AMG 073 or placebo (632 +/- 280.1 pg/mL vs. 637 +/- 455.9 pg/mL, respectively). PTH decreased by 26.0% in the AMG 073-treated group, compared with an increase of 22.0% in the placebo group (P < 0.001). A greater proportion in the AMG 073 group (38%) had a decrease in PTH >or=30%, compared with the placebo group (8%) (P = 0.001). Decreases in PTH were independent of baseline vitamin D usage. Patients receiving AMG 073 had an 11.9% decrease in calcium x phosphorus compared with a 10.9% increase in the placebo group (P < 0.001). Use of vitamin D sterols, as well as both calcium and noncalcium-containing phosphate binders. were similar between treatment groups. Administration of AMG 073 was safe and well tolerated in this 18-week study.
                The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism. Current phosphate binders used in hemodialysis patients include calcium-based binders that result in frequent hypercalcemia. The use of a calcium- and aluminum-free phosphate-binding polymer in hemodialysis (sevelamer) disclosed efficacy in the short and long-term studies. However, due to race differences we performed a short-term study on the Saudi hemodialysis patients and compared sevelamer with a standard calcium-based phosphate binder.
                An open-label, randomized, cross-over study was performed to evaluate the safety and effectiveness of sevelamer hydrochloride in controlling hyperphosphatemia in hemodialysis patients. After a 2-week phosphate binder washout period, stable hemodialysis patients were given either sevelamer or calcium carbonate, and the dosages were titrated to achieve phosphate control over an 8-week period. After a 2-week washout period, patients crossed over to the alternate agent for 8 weeks. Twenty patients from the Dialysis Unit of King Fahd Hospital, Jeddah, Kingdom of Saudi Arabia, were recruited for the study between March 2003 and June 2003.
                There was a similar decrease in serum phosphate values over the course of the study with both sevelamer (-3.3 +/-2.2 mg/dL) and calcium carbonate (-3.9 +/-2.8 mg/dL). Fifty-two percent of patients developed serum calcium greater than 2.75 mmol/L (11.0 mg/dL) while receiving calcium carbonate versus 26% of patients receiving sevelamer (p<0.05). The incidence of hypercalcemia for sevelamer was not different from the incidence of hypercalcemia during the washout period. Patients treated with sevelamer also sustained a 13% mean decrease in serum cholesterol levels.
                Sevelamer was effective in controlling hyperphosphatemia without resulting in an increase in the incidence of hypercalcemia seen with calcium carbonate. This agent appears quite effective in the treatment of hyperphosphatemia in hemodialysis patients, and its usage may be advantageous in the treatment of dialysis patients. This study was designed to evaluate the efficacy of magnesium carbonate as a phosphate binder in hemodialysis patients.
                This study was a prospective, randomized, open-label trial comparing magnesium carbonate/calcium carbonate versus calcium acetate as a sole phosphate binder.
                This study involved outpatient hemodialysis.
                We recruited 30 stable hemodialysis patients without a history of frequent diarrhea.
                After receiving informed consent, we randomized patients 2:1 to magnesium carbonate versus calcium acetate. The dose of each binder was titrated to achieve the Kidney Disease Outcomes Quality Initiative (K/DOQI) phosphate target of <5.5 mg/dL.
                The efficacy-phase serum phosphorus concentration and the percentage of patients meeting K-DOQI targets for phosphorus, along with the daily elemental calcium intake, were the primary outcome measures.
                Magnesium carbonate provided equal control of serum phosphorus (70.6% of the magnebind group and 62.5% of the calcium acetate group had their average serum phosphorus within the K-DOQI target during the efficacy phase), while significantly reducing daily elemental calcium ingestion from phosphate binders (908 +/- 24 vs. 1743 +/- 37 mg/day, P < .0001).
                Magnesium carbonate was generally well-tolerated in this selected patient population, and was effective in controlling serum phosphorus while reducing elemental calcium ingestion. Sucralfate has been reported to reduce serum phosphate concentration in patients with chronic renal failure. To evaluate whether sucralfate could be used to treat hyperphosphatemia secondary to chronic renal failure and whether this treatment resulted in a reduced exposure to aluminum, an open-label crossover study was designed to determine the efficacy, relative potency, safety, and cost of sucralfate v aluminum hydroxide. Of the 21 hemodialysis patients completing both phases of the crossover study, serum phosphate could be maintained below 4.5 mg/dL (1.45 mmol/L) in 16 with sucralfate and in 14 with aluminum hydroxide. The 16 patients controlled on sucralfate consumed 1,694 +/- 190 mg/d of aluminum to maintain a serum phosphate concentration of 3.91 +/- 0.17 mg/dL (1.27 +/- 0.05 mmol/L) compared with the 14 patients controlled on aluminum hydroxide with an aluminum intake of 2,678 +/- 294 mg/d (P less than 0.025) and a serum phosphate concentration of 3.94 +/- 0.13 mg/dL (1.27 +/- 0.04 mmol/L). Thus sucralfate was an effective, albeit expensive, alternative to aluminum hydroxide for the treatment of hyperphosphatemia associated with chronic renal failure. Although the difference in aluminum intake was significant, use of sucralfate did not result in lower serum aluminum concentrations. Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology.
                101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months.
                The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 +/- 352 vs. 326 +/- 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 +/- 24 vs. 28 +/- 15 U/l, p = 0.03) and deoxypyridinoline (135 +/- 107 vs. 89 +/- 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 +/- 21 vs. 91 +/- 28 mg/dl, p = 0.015). Phosphorus (5.8 +/- 1.0 vs. 6 +/- 1.0 mg/dl, p = 0.47) and calcium (1.27 +/- 0.07 vs. 1.23 +/- 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 +/- 5.9 vs. 13.1 +/- 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 +/- 0.016 vs. 0.062 +/- 0.078, p = 0.003 for calcium and 0.017 +/- 0.016 vs. 0.071 +/- 0.084 microm(3)/microm(2)/day, p = 0.010 for sevelamer).
                There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups.
                (c) 2008 S. Karger AG, Basel. To investigate the evolution of renal osteodystrophy in patients on maintenance dialysis, treated with lanthanum carbonate (LC) vs. standard phosphate-binder therapy (Stx).
                This was a 2-year, randomized, prospective, open-label study during which patients on dialysis received LC titrated to a maximum of 3,000 mg/day or their previous phosphate binder treatment with the aim to achieve target phosphorus levels of < or = 5.9 mg/dl. Paired bone biopsy samples for histomorphometric analysis were available at baseline and 1 year (LC 32, Stx 33), and at baseline and 2 years (LC 32, Stx 24).
                With similar phosphorus control, Stx was associated with numerically higher serum calcium levels at most visits. Results of osteocalcin and bone-specific alkaline phosphatase in LC patients were higher throughout the study and correlated with parameters of bone formation; however, the differences were not significant. Histological changes in bone turnover and volume were analyzed with respect to normal ranges. There was an improvement in bone turnover in the LC group, which was significant in the 1-year group, and an improvement in bone volume which was significant in the 2-year group. No significant changes in bone turnover or bone volume were observed in the Stx groups. In the 2-year LC group, 1 patient had osteomalacia at baseline and end of therapy, and a mineralization defect developed in 2 other patients. Several possible factors for a mineralization defect were present in these patients, but no single cause could be clearly identified. Histomorphometric parameters of bone, including formation and mineralization, did not correlate with bone lanthanum. No mineralization defect was observed in the Stx groups.
                These findings show that similar phosphorus control with Stx and LC results in higher bone turnover after 1 year and higher bone volume after 2 years with LC. The hyperphosphatemia, hypocalcemia and low calcitriol levels are pathogenic factors for secondary hyperparathyroidism in chronic renal failure. The phosphorus control is essential to prevent secondary hyperparathyroidism. There are not comparatives studies to test the efficacy of control of phosphorus binders in predialysis patients.
                To compare the efficacy of calcium carbonate vs calcium acetate as phosphate binder in predialysis patients.
                The present study includes 28 patients with chronic renal failure (mean clearance of creatinine 21 ml/min). Patients were separated into two groups: Group 1: (n = 14) received calcium carbonate 2,500 mg/day (1,000 mg of calcium); Group 2: (n = 14) receives calcium acetate 1,000 mg (254 mg of calcium). Calcium and phosphorus were determined every 4 months; i-PTH, alkaline phosphatase and clearance of creatinine were determined every six months.
                Both groups were comparable regarding age, renal function, calcium, phosphorus, alkaline phosphatase and i-PTH on basal situation and the end of study were not different. The serum calcium increased, not significantly, in the calcium carbonate group (group 1) [from 9.2 to 9.8 mg/dl (p = 0.05)], however it was not modified in the calcium acetate group (group 2). The serum phosphorus decreased significantly (p < 0.05) in both groups, independently of the calcium levels. Alkaline phosphatase and i-PTH not was modified during the study period.
                1) Both calcium carbonate and calcium acetate are similarly effective as phosphate binder. 2) The carbonate group required four fold greater doses of calcium that acetate group. 3) The calcium acetate has less hypercalcemic effect than calcium carbonate. Patients with renal failure require complex regimens of renal replacement therapies and medications, including ingestion of phosphate-binding agents 3 times daily. Previous studies suggested that sevelamer may provide extended phosphate binding and be effective with once-daily dosing, thus simplifying the phosphate-binder regimen.
                Twenty-four patients were enrolled in this study, 21 of whom were randomly assigned to sevelamer administration at their previously prescribed dose, either once daily with the largest meal or thrice daily with meals, with crossover to the other regimen after 4 weeks. Eighteen patients completed both treatment periods. The primary efficacy measure for which the study was powered is comparison of the effect of once-daily versus standard thrice-daily sevelamer dosing on serum phosphorus level control, determined by using equivalence testing. Secondary efficacy measures are the effects of the 2 regimens on serum calcium level corrected for albumin level; calcium x phosphorus product; albumin; intact parathyroid hormone; total, low-density lipoprotein, high-density lipoprotein, and non-high-density lipoprotein cholesterol; and triglyceride levels.
                Once-daily sevelamer was as effective as thrice-daily dosing of sevelamer in controlling serum phosphorus, calcium, calcium x phosphorus product, serum albumin, and serum lipid levels. Bioequivalence was not shown for intact parathyroid hormone, likely because of high variability. Mean serum phosphorus levels were 4.6 +/- 0.3 mg/dL (1.49 +/- 0.10 mmol/L) during thrice-daily dosing and 5.0 +/- 0.3 mg/dL (1.61 +/- 0.10 mmol/L) during once-daily dosing. The average prescribed dose of sevelamer during both treatment regimens was 6.7 +/- 2.4 g. Routine laboratory measures were similar in the 2 groups. Both regimens were well-tolerated.
                Despite concerted patient-directed educational efforts, phosphorus level control in patients with renal failure is suboptimal and contributes to increased mortality risk. Once-daily sevelamer could simplify these regimens and encourage medication compliance, perhaps improving hyperphosphatemia management. We examined the biochemical changes and the efficacy of indapamide in the prevention of calcium stone recurrences. Seventy-five patients with calcium nephrolithiasis and hypercalciuria were randomly assigned to three different therapies: diet and fluid (group A), diet and fluid plus indapamide 2.5 mg/day (group B), and diet and fluid plus indapamide 2.5 mg/day plus allopurinol 300 mg/day (group C). Before treatment and after 6, 12, 24, and 36 months of therapy, we evaluated blood pressure, serum and urine risk parameters (including relative supersaturations of calcium oxalate, calcium phosphate and uric acid), stone rate, and the proportion of calculi-free patients. During the 3 years of treatment, urinary calcium greatly decreased in groups B and C, dropping to 50% of the pretreatment values; urinary oxalate also significantly declined in group B (-24%) and group C (-27%). Relative supersaturations of calcium oxalate and calcium phosphate decreased to the same extent in groups B and C (about one-half of the pretreatment value), and relative supersaturation of uric acid was particularly reduced in group C (-65% of the pretreatment value). The stone rate improved in all three groups (p < 0.005), but using actuarial analysis in the evaluation of calculi-free patients, indapamide, and indapamide plus allopurinol groups were found to have a significantly more favorable effect than diet and fluid treatment (p < 0.02), without any difference between the two drug groups. Because indapamide has fewer side effects than thiazide diuretics, we conclude that indapamide could be an interesting alternative to thiazides in the prevention of calcium stones in hypercalciuric patients. Magnesium salts bind dietary phosphorus, but their use in renal patients is limited due to their potential for causing side effects. The aim of this study was to evaluate the efficacy and safety of magnesium carbonate (MgCO(3)) as a phosphate-binder in hemodialysis patients.
                Forty-six stable hemodialysis patients were randomly allocated to receive either MgCO(3) (n=25) or calcium carbonate (CaCO(3)), (n=21) for 6 months. The concentration of Mg in the dialysate bath was 0.30 mmol/l in the MgCO(3) group and 0.48 mmol/l in the CaCO(3) group.
                Only two of 25 patients (8%) discontinued ingestion of MgCO(3) due to complications: one (4%) because of persistent diarrhea, and the other (4%) because of recurrent hypermagnesemia. In the MgCO(3) and CaCO(3) groups, respectively, time-averaged (months 1-6) serum concentrations were: phosphate (P), 5.47 vs. 5.29 mg/dl, P=ns; Ca, 9.13 vs. 9.60 mg/dl, P<0.001; Ca x P product, 50.35 vs. 50.70 (mg/dl)(2), P=ns; Mg, 2.57 vs. 2.41 mg/dl, P=ns; intact parathyroid hormone (iPTH), 285 vs. 235 pg/ml, P<0.01. At month 6, iPTH levels did not differ between groups: 251 vs. 212 pg/ml, P=ns. At month 6 the percentages of patients with serum levels of phosphate, Ca x P product and iPTH that fell within the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines were similar in both groups, whereas more patients in the MgCO(3) group (17/23; 73.91%) than in the CaCO(3) group (5/20, 25%) had serum Ca levels that fell within these guidelines, with the difference being significant at P<0.01.
                Our study shows that MgCO(3) administered for a period of 6 months is an effective and inexpensive agent to control serum phosphate levels in hemodialysis patients. The administration of MgCO(3) in combination with a low dialysate Mg concentration avoids the risk of severe hypermagnesemia. There is no generally accepted treatment for primary focal segmental glomerulosclerosis (FSGS). Steroids alone and steroids plus cyclophosphamide can be expected to induce a remission of the proteinuria in only 27% of patients. Probably the majority of FSGS patients will reach ESRD over the extended course of their disease. In addition to the work presented in this study, there have been many reports of the potential effectiveness of cyclosporine (CSA) on reducing the proteinuria of FSGS. This study was undertaken to test the efficacy and safety of a 6-month course of CSA in a double-blinded, prospectively randomized, placebo-controlled trial in children with corticosteroid-resistant FSGS. The potential inhibitory effect of hypercholesterolemia on the proteinuria-reducing actions of CSA was also assessed. Twenty-five patients with FSGS were randomized to receive either placebo or CSA for 6 months. Twelve of the 12 patients that received CSA experienced a diminution of their proteinuria as opposed to only two of the 12 placebo-treated patients. Proteinuria was significantly reduced from 151.7 +/- 162.4 mg/kg per 24 h at Week 0 to 36.9 +/- 42.3 at the end of the study in the group that received CSA (P < 0.05). There was no significant change in the proteinuria of the patients in the placebo group. A significant correlation between the percentage change of proteinuria over the 6 months of the study and the prestudy serum cholesterol levels (r = 0.79, P < 0.05) was seen in the CSA group. A partial correlation analysis controlling for the effects of serum cholesterol uncovered a significant relationship between average CSA level and proteinuria change (r = -0.76, P < 0.05). The fractional decline in GFR over the course of the study was not significantly different between the CSA and placebo-treated groups. In conclusion, CSA reduces proteinuria, increases serum albumin levels, and can be expected, therefore, to reduce the symptoms of nephrotic syndrome. Hypercholesterolemia antagonizes this effect of CSA. Hyperphosphatemia is common in end-stage renal disease patients. Objective of this study is to compare the hypercalcaemic effect and phosphate binding power of calcium acetate and calcium carbonate in end-stage renal disease patients on maintenance haemodialysis.
                This randomised control trial was conducted in four phases with calcium acetate or calcium carbonate. Sixty-four patients on haemodialysis were randomly divided into 2 groups. After a washout period of 2 weeks, each group was given calcium acetate or calcium carbonate for 2 months. After another washout period the patients were crossed over and again received these drugs for 2 months. Serum Calcium, phosphate, and albumin were analysed on Selectra E auto analyser at completion of each phase of study. Hypercalcaemic effect was defined as serum calcium > 2.54 mmol/l, and phosphate binding power as serum phosphate < 1.61 mmol/l.
                Forty-one patients completed the study. Though lower dose of calcium acetate was used, it resulted in equally good control of hyperphosphatemia as compared with calcium carbonate therapy [1.37 mmol/l (SD 0.33) vs. 1.46 mmol/l (SD 0.34), p = 0.16]. Incidence of hypercalcaemia was higher with calcium carbonate therapy (2.73 +/- 0.67 mmol/l vs. 2.32 +/- 0.28 mmol/l, p < 0.01). Both drugs were well tolerated, but patients more frequently complained of muscle cramps while taking calcium acetate.
                It is concluded that calcium acetate has similar effect on serum phosphate levels as compared to calcium carbonate in patients on maintenance haemodialysis. However, calcium acetate results in lesser frequency of hypercalcaemia as compared to calcium carbonate. Tolerance to both drugs was similar, though patients complained of more muscle cramps while taking calcium acetate. Hyperphosphataemia contributes to secondary hyperparathyroidism and renal osteodystrophy in patients with end-stage renal disease (ESRD). Calcium salts are widely employed to bind dietary phosphate (P) but they may promote positive net calcium balance and metastatic calcification. We recently reported that ferric compounds bind intestinal phosphate in studies of normal and azotemic rats.
                To extend this observation, we performed an open-label, random order, crossover comparison study of ferric citrate and calcium carbonate in haemodialysis patients from two teaching hospitals. The study sample consisted of 23 women and 22 men with an average age of 52.5 +/- 11.8 (SD) years and an average weight of 54.5 +/- 10.7 kg. All forms of iron therapy were discontinued. Two weeks before the study, patients were instructed to discontinue all P-binding agents. The patients were randomly assigned to receive either calcium carbonate (3 g/day) or ferric citrate (3 g/day) for 4 weeks followed by a 2 week washout period, and then crossed over to the other P-binding agent for 4 weeks.
                From a baseline concentration of 5.6 +/- 1.5 mg/dl, the serum P increased during the washout period to 7.2 +/- 1.9 mg/dl prior to calcium carbonate treatment, and to 6.7 +/- 1.9 mg/dl prior to ferric citrate treatment. The serum P concentration fell significantly during treatment with both calcium carbonate (7.2 +/- 1.9 to 5.2 +/- 1.5 mg/dl, P<0.0001) and ferric citrate (6.7 +/- 1.9 to 5.7 +/- 1.6 mg/dl, P<0.0001). The results were not influenced by order of treatment. Under the conditions of the study protocol, ferric citrate was less effective than calcium carbonate at lowering the serum phosphate concentration. The serum Ca concentration increased during treatment with calcium carbonate but not ferric citrate. Ferric citrate treatment did not affect the serum concentration of aluminium. Ferric citrate treatment was associated with mild and generally tolerable gastrointestinal symptoms.
                Ferric citrate shows promise as a means of lowering the serum phosphate concentration in haemodialysis patients. Further studies are needed to find the optimal dose. Since hyperphosphatemia in hemodialysis patients can cause secondary hyperparathyroidism and promotes vascular calcification, serum phosphate (Pi) levels must be controlled by phosphate binders. Although sevelamer and colestimide are known as similar non-calcium, non-aluminum phosphate binders in hemodialysis patients, there are no studies that compare the effects of the two agents as either a monotherapy or in combination with calcium carbonate (CaCO3). We randomly allocated 62 hemodialysis patients with hyperphosphatemia to treatment with sevelamer (3.0 g/day) and colestimide (3.0 g/day). During the study, 35 subjects dropped out, leaving 13 in the sevelamer group and 14 in the colestimide group. After a 2-week CaCO3 washout, all subjects received the monotherapy for 4 weeks and then CaCO3 (3.0 g/day) was added for another 4 weeks. Serum corrected calcium levels tended to decrease in both groups during the washout period and monotherapy, but there was no significant difference between the two groups after the addition of CaCO3. Although the calcium x phosphorus product (Ca x P) in the two groups increased during the washout period, there was no significant change or difference between the two groups during monotherapy. However, the addition of CaCO3 significantly reduced serum Pi at Week 8 compared to that at Week 0 in both groups, and significantly lowered Ca x P only in the sevelamer group, but not in the colestimide group(.) In this short-term study, sevelamer and colestimide similarly ameliorated hyperphosphatemia, but the combination of sevelamer and CaCO3 was more effective than colestimide with CaCO3 in controlling the Ca x P product, and it may improve cardiovascular mortality in hemodialysis patients. Cardiovascular disease is frequent and severe in patients with end-stage renal disease. Disorders of mineral metabolism may contribute by promoting cardiovascular calcification.
                We conducted a randomized clinical trial comparing sevelamer, a non-absorbed polymer, with calcium-based phosphate binders in 200 hemodialysis patients. Study outcomes included the targeted concentrations of serum phosphorus, calcium, and intact parathyroid hormone (PTH), and calcification of the coronary arteries and thoracic aorta using a calcification score derived from electron beam tomography.
                Sevelamer and calcium provided equivalent control of serum phosphorus (end-of-study values 5.1 +/- 1.2 and 5.1 +/- 1.4 mg/dL, respectively, P = 0.33). Serum calcium concentration was significantly higher in the calcium-treated group (P = 0.002), and hypercalcemia was more common (16% vs. 5% with sevelamer, P = 0.04). More subjects in the calcium group had end-of-study intact PTH below the target of 150 to 300 pg/mL (57% vs. 30%, P = 0.001). At study completion, the median absolute calcium score in the coronary arteries and aorta increased significantly in the calcium treated subjects but not in the sevelamer-treated subjects (coronary arteries 36.6 vs. 0, P = 0.03 and aorta 75.1 vs. 0, P = 0.01, respectively). The median percent change in coronary artery (25% vs. 6%, P = 0.02) and aortic (28% vs. 5%, P = 0.02) calcium score also was significantly greater with calcium than with sevelamer.
                Compared with calcium-based phosphate binders, sevelamer is less likely to cause hypercalcemia, low levels of PTH, and progressive coronary and aortic calcification in hemodialysis patients. Since dietary restrictions and phosphorus removal by haemodialysis (HD) are not sufficient to control serum phosphate (s-phosphate) levels in dialysis patients the use of oral phosphate binders is mandatory. Calcium ketoglutarate (CaKE) is an analogue of glutamic acid exerting phosphate binding properties. Therefore we compared this substance to calcium acetate (CaAC) in a 24-weeks open cross-over trial in 28 maintenance HD patients. Medications and HD prescriptions were kept unchanged during the trial. Following 2 weeks of withdrawal of phosphate binders, patients were randomly assigned to one of the calcium salts for 12 weeks; after a second withdrawal of 2 weeks, all patients were shifted to the other treatment for another 12 weeks. All patients received equimolar doses of CaKE and CaAC with respect to the amount of prescribed elemental calcium. Treatment with CaAC and CaKE significantly reduced s-phosphate levels after 4 weeks (CaAC 1.95+/-0.6 vs. 2.4+/-0.53 mmol/l, P = 0.004; CaKE 1.95+/-0.4 vs. 2.47+/-0.63 mmol/l, P = 0.0001) reaching a virtually stable plateau over the remaining observation time without significant differences between the groups. The incidence of hypercalcaemia defined as a serum calcium level > or =2.8 mmol/l was significantly higher in CaAC than in CaKE treated patients (n = 8 vs. n = 1, P = 0.03). There were no significant differences in serum intact parathyroid hormone (PTH) bicarbonate, albumin or calcitriol levels between the groups after 12 weeks treatment. We conclude that CaKE is as effective as CaAC for treatment of hyperphosphataemia in chronic HD patients and may be particularly helpful in patients who are prone to develop hypercalcaemia. Management of hyperphosphatemia, a predictor of mortality in chronic kidney disease, is challenging. Nonadherence to dietary phosphate binders, in part, contributes to uncontrolled serum phosphorus levels. This phase IIIb trial assessed the efficacy of increased dosages (3000 to 4500 mg/d) of reformulated lanthanum carbonate (500-, 750-, and 1000-mg tablets) in nonresponders to dosages of up to 3000 mg/d.
                This 8-wk study with a 4-mo open-label extension enrolled 513 patients who were undergoing maintenance hemodialysis. Patients who achieved serum phosphorus control at week 4 with <or=3000 mg/d lanthanum carbonate entered cohort A; nonresponders were randomly assigned to receive 3000, 3750, or 4500 mg/d (cohort B). The primary outcome measure was the control rate for predialysis serum phosphorus levels at the end of week 8, among patients in cohort B.
                At the end of week 4, 54% of patients achieved serum phosphorus control at dosages <or=3000 mg/d administered as one tablet per meal. Among patients who entered cohort B, control rates of 25, 38, and 32% for patients who were randomly assigned to 3000, 3750, or 4500 mg/d lanthanum carbonate, respectively, were achieved, with no increase in adverse events. Patients and physicians reported significantly higher levels of satisfaction with reformulated lanthanum carbonate compared with previous phosphate binders, partly because of reduced tablet burden with higher dosage strengths. Physicians and patients also expressed a preference for lanthanum carbonate over previous medication.
                Reformulated lanthanum carbonate is an effective phosphate binder that may reduce daily tablet burden. Bone mineral content, estimated by single-photon absorptiometry of the forearm, serum values of intact parathyroid hormone (PTH(1-84], osteocalcin, alkaline phosphatase, 1,25-dihydroxycholecalciferol (1,25(OH)2D3), and aluminium were determined during treatment with calcium carbonate (CaCO3) or aluminium hydroxide (Al(OH)3) in 11 dialysis patients participating in a randomised cross-over study. Each treatment period lasted 6 months. Serum phosphorus was maintained in the range 1.5-2.0 mmol/l. During Al(OH)3 treatment bone mineral content (BMC) decreased by 11% per half-year (mean), but only by 3% per half-year during CaCO3 treatment (P less than 0.05). Comparing the CaCO3 and Al(OH)3 periods the following differences were found: serum calcium increased during CaCO3 treatment, PTH(1-84) decreased (79% of initial values during CaCO3 versus 196% during Al(OH)3, mean area under curve, P less than 0.05), osteocalcin decreased (89% versus 117%, P less than 0.01), alkaline phosphatase decreased (92% versus 116%, P less than 0.05), and aluminium decreased (56% versus 189%, P less than 0.05). 1,25(OH)2D3 remained unchanged in both periods. No increase in soft-tissue calcification was demonstrated on X-ray of the shoulders in any of the periods. Thus, CaCO3 treatment seems to slow down loss of bone mineral content, and using CaCO3 as phosphate binder may have a more beneficial effect on the progression of uraemic bone disease than Al(OH)3 due to the reduction of hyperparathyroidism and bone turnover. Recent in vitro and in vivo studies have shown that calcium acetate (CaAC) is a more effective phosphorus binder than, among other calcium salts, calcium carbonate (CaCO3). More efficient binding allows serum phosphorus to be controlled with a lower dose; moreover, less calcium seems to be absorbed when CaAC is used. These properties could reduce the incidence of hypercalcemia; however, in clinical practice few reports have compared these two calcium salts, and results disagree. We evaluated in a 24-week prospective cross-over study the clinical efficiency of CaCO3 and CaAC in 10 selected chronic hemodialysis patients. Only 7 patients completed the study period. The patients were randomly assigned to start treatment with one of the two calcium salts; after 12 weeks they shifted to the other treatment. Serum analytical tests included weekly control of calcium, phosphorus, and alkaline phosphatase. PTH values (intact molecule) were obtained initially and at the end of every study period. The same good control of the phosphorus level (4.79 +/- 0.6 vs. 4.94 +/- 0.8 mg/dl) was obtained with CaAC (mean doses 4.1 +/- 0.3 g/day) as with CaCO3 (mean doses 4.01 +/- 0.8 g/day). The mean serum calcium levels were similar (10.36 +/- 0.5 vs. 10.20 +/- 0.5 mg/dl). The dose of elemental calcium administered was significantly less with CaAC (957 +/- 83 mg/day) than with CaCO3 (1,590 +/- 317 mg/day). However, the incidence of hypercalcemia (Ca > 11 mg/dl) was similar during the two treatment periods (13% with CaAC vs. 14% with CaCO3). Also the incidence of Ca x P products 765 was comparable (9.5 vs. 11.9%).(ABSTRACT TRUNCATED AT 250 WORDS) Hyperphosphatemia is an important clinical consequence of renal failure, and its multiple adverse systemic effects are associated with significantly increased risks of morbidity and mortality in dialysis patients. Existing oral phosphate binders have not permitted control of serum phosphate within currently accepted guidelines. This study compares lanthanum carbonate with calcium carbonate for control of serum phosphate in hemodialysis patients.
                In this European multicentre study, 800 patients were randomised to receive either lanthanum or calcium carbonate and the dose titrated over 5 weeks to achieve control of serum phosphate. Serum levels of phosphate, calcium and parathryoid hormone were followed over the following 20 weeks.
                Around 65% of patients in each group achieved phosphate control, but in the calcium carbonate group this was at the expense of significant hypercalcemia (20.2% of patients vs. 0.4%). Consequently, calcium x phosphate product tended to be better controlled in the lanthanum group.
                This 6-month study demonstrates that serum phosphate control with lanthanum carbonate (750-3,000 mg/day) is similar to that seen with calcium carbonate (1,500-9,000 mg/day), but with a significantly reduced incidence of hypercalcemia. Lanthanum carbonate is well tolerated and may be more effective in reducing calcium x phosphate product than calcium carbonate. A randomized controlled trial was conducted involving 67 stable adult haemodialysis patients with hyperphosphataemia. The objective was to determine the effect of monthly dietetic consultations on patients' serum phosphate concentrations and calcium x phosphate product.
                The intervention group received monthly dietetic consultations for 6 months using advanced counselling skills aimed at limiting phosphate intake in the diet and improving compliance with phosphate binders, whereas standard care with dietetic consultations every 6 months was provided to the control group.
                Serum phosphate concentrations decreased in the intervention group from 2.05 +/- 0.48 to 1.80 +/- 0.48 mmol/l by month 3 (p < 0.05). However, this subsequently increased and by month 6 there was no significant difference from baseline. After controlling for confounding variables, the difference between the groups was approaching significance at month 3, but there was no difference by month 6, or following conclusion of the study. The calcium x phosphate product similarly decreased in both groups, achieving K/DOQI standards, but was not sustained either during the remainder of the study but decreased further by the 12-month follow-up and, although it was not significantly different, it did improve significantly from baseline in both the intervention and control groups.
                Increased frequency of dietetic consultations can result in improved phosphate control in the short term, and therefore more innovative strategies appear necessary to sustain longer-term control.
                Copyright 2008 S. Karger AG, Basel. The objective of the study was to evaluate the phosphate-binding efficacy, side effects, and cost of therapy of calcium ketoglutarate granulate as compared with calcium carbonate tablets in patients on chronic hemodialysis. The study design used was a randomized, crossover open trial, and the main outcome measurements were plasma ionized calcium levels, plasma phosphate levels, plasma intact parathyroid hormone (PTH) levels, requirements for supplemental aluminum-aminoacetate therapy, patient tolerance, and cost of therapy. Nineteen patients on chronic hemodialysis were treated with a dialysate calcium concentration of 1.25 mmol/L and a fixed alfacalcidol dose for at least 2 months. All had previously tolerated therapy with calcium carbonate. Of the 19 patients included, 10 completed both treatment arms. After 12 weeks of therapy, the mean (+/-SEM) plasma ionized calcium level was significantly lower in the ketoglutarate arm compared with the calcium carbonate arm (4.8+/-0.1 mg/dL v 5.2+/-0.1 mg/dL; P = 0.004), whereas the mean plasma phosphate (4.5+/-0.3 mg/dL v 5.1+/-0.1 mg/dL) and PTH levels (266+/-125 pg/mL v 301+/-148 pg/mL) did not differ significantly between the two treatment arms. Supplemental aluminum-aminoacetate was not required during calcium ketoglutarate treatment, while two patients needed this supplement when treated with calcium carbonate. Five of 17 (29%) patients were withdrawn from calcium ketoglutarate therapy within 1 to 2 weeks due to intolerance (anorexia, vomiting, diarrhea, general uneasiness), whereas the remaining 12 patients did not experience any side effects at all. The five patients with calcium ketoglutarate intolerance all had pre-existing gastrointestinal symptoms; four of them had received treatment with cimetidine or omeprazol before inclusion into the study. Calculations based on median doses after 12 weeks showed that the cost of the therapy in Denmark was 10 times higher for calcium ketoglutarate compared with calcium carbonate (US$6.00/d v US$0.65/d). Calcium ketoglutarate may be an effective and safe alternative to treatment with aluminum-containing phosphate binders in patients on hemodialysis who are intolerant of calcium carbonate or acetate because of hypercalcemia. However, care must be exercised when dealing with patients with pre-existing gastrointestinal discomfort. Due to the high cost of the therapy, calcium ketoglutarate should be used only for selected patients. Preliminary results from clinical trials suggest that 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors may help prevent acute renal allograft rejection. However, the mechanism for this putative effect of 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, and whether it is independent of lipid-lowering per SE are unknown.
                Immediately after renal transplantation we randomly allocated (proportioned 2:1:2) patients to: 1) simvastatin (10 mg/day, n=53), 2) simvastatin placebo plus gemfibrozil (dose adjusted for renal function, n=36), and 3) simvastatin placebo (n=52).
                Simvastatin, but not gemfibrozil, reduced total and low density lipoprotein cholesterol during the first 90 days posttransplant. There were no major adverse effects of therapy. However, there were no effects of treatment on acute rejection. Indeed, survival free of acute rejection at 90 days was 72% in the simvastatin group, 72% in the gemfibrozil group, and 77% in the placebo control group (P=0.771). A post hoc power analysis suggested that there was only a 7.5% chance that a true effect of simvastatin on acute rejection (versus placebo) was not detected, and a 2.5% chance that an effect of gemfibrozil on acute rejection (versus placebo) was not detected in this study.
                Lipid-lowering agents may not reduce the incidence of acute renal allograft rejection. However, additional studies are needed to confirm this observation. In the mean time, many if not most renal transplant recipients should be treated with HMG-CoA reductase inhibitors starting early posttransplant to prevent cardiovascular disease complications. The results of this study suggest that starting lipid-lowering therapy immediately after renal transplantation is both safe and effective in lowering total and low density lipoprotein cholesterol. We assessed the effect of a severe hypoproteic diet supplemented with ketoanalogues (SVLPD) for 48 weeks on certain metabolic disorders of chronic kidney disease (CKD).
                We performed a prospective, open-label, parallel, randomized, controlled trial.
                The study took place in the Nephrology Department at the Dr Carol Davila Teaching Hospital of Nephrology, Bucharest, Romania.
                A total of 53 nondiabetic patients with CKD with an estimated glomerular filtration rate less than 30 mL/min/1.73 m(2) (Modification of Diet in Renal Disease formula), proteinuria less than 1 g/g urinary creatinine, good nutritional status, and anticipated good compliance with the diet were randomly assigned to two groups.
                Group I (n = 27) received the SVLPD (0.3 g/kg/d of vegetable proteins and ketoanalogues, 1 capsule for every 5 kg of ideal body weight per day). Group II (n = 26) continued a conventional low mixed protein diet (0.6 g/kg/d).
                Nitrogen waste products retention and calcium-phosphorus and acid-base disturbances were primary efficacy parameters, and "death" of the kidney or the patient and the estimated glomerular filtration rate were secondary efficacy parameters. The nutritional status and compliance with the diet were predefined as safety variables. There were no differences between groups in any parameter at baseline.
                In the SVLPD group, serum urea significantly decreased (56 +/- 7.9 mmol/L vs. 43.2 +/- 10 mmol/L), and significant improvements in serum bicarbonate (23.4 +/- 2.1 mmol/L vs. 18.1 +/- 1.5 mmol/L), serum calcium (1.10 +/- 0.17 mmol/L vs. 1.00 +/- 0.15 mmol/L at baseline), serum phosphates (1.45 +/- 0.66 mmol/L vs. 1.91 +/- 0.68 mmol/L), and calcium-phosphorus product (1.59 +/- 0.11 mmol(2)/L(2) vs. 1.91 +/- 0.10 mmol(2)/L(2)) were noted after 48 weeks. No death was registered in any group. Significantly lower percentages of patients in group I required renal replacement therapy initiation (4% vs. 27%). After 48 weeks, estimated glomerular filtration rate did not significantly change in patients receiving SVLPD (0.26 +/- 0.08 mL/s vs. 0.31 +/- 0.08 mL/s at baseline), but significantly decreased in controls (0.22 +/- 0.09 mL/s vs. 0.30 +/- 0.07 mL/s). The compliance with the keto-diet was good in enrolled patients. No significant changes in any of the parameters of the nutritional status and no adverse reactions were noted.
                SVLPD seems to ameliorate the nitrogen waste products retention and acid-base and calcium-phosphorus metabolism disturbances and to postpone the renal replacement therapy initiation, preserving the nutritional status in patients with CKD. We examined the physiological effects and tolerance of UroPhos-K, a slow release neutral form of potassium phosphate (155 mg. phosphate and 8 mEq. potassium per tablet) in patients with absorptive hypercalciuria.
                A total of 31 patients with absorptive hypercalciuria were studied at baseline and after 3 months of treatment with 4 tablets twice daily of UroPhos-K or placebo (identical in appearance) in a prospective randomized, placebo controlled, double-blind trial during a 4-day inpatient study with a daily constant metabolic diet containing 400 mg. calcium, 100 mEq. sodium and 800 mg. phosphate.
                Treatment with UroPhos-K did not cause significant gastrointestinal side effects, increase fasting serum potassium or phosphorus, or reduce hemoglobin or creatinine clearance. It reduced urinary calcium excretion from 277 +/- 72 to 166 +/- 43 mg. per day (p < 0.001), associated with a reduction in serum 1,25-dihydroxyvitamin D concentration from 50 +/- 11 to 42 +/- 9 pg./ml. (p < 0.001). Indexes of intestinal calcium absorption and markers of bone turnover also decreased modestly. None of these changes was seen in the placebo group.
                In patients with absorptive hypercalciuria UroPhos-K seems to correct hypercalciuria by a combination of reduced intestinal absorption, bone resorption and improved renal calcium reabsorption. The drug is well tolerated compared to placebo. 24 patients with chronic renal failure (glomerular filtration-rate (G.F.R.) 5-25 ml/min) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol (1alpha-H.C.C.) 1 mug daily for eleven weeks. This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks. It also induced a significant reduction of the raised serum levels of parathyroid hormone. No significant changes were induced in plasma-phosphorus, plasma-alkaline-phosphatase, or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone. The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group. The fall in G.F.R. over eleven weeks was 2-5 times greater in the 1alpha-H.C.C. group than in the placebo group, but this difference was not significant. It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium. The safety and efficacy of paricalcitol injection have been well established for the prevention and treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) stage 5. The capsule form of paricalcitol was developed to provide a convenient dosage form for patients with stages 3 and 4 CKD.
                Three randomized, placebo-controlled, phase-3 trials were conducted in patients with stages 3 and 4 CKD with SHPT. Enrollment criteria included an estimated glomerular filtration rate between 15 and 60 mL/min/1.73 m2 (0.25 and 1.00 mL/s/1.73 m2), an average of 2 consecutive intact parathyroid hormone (iPTH) levels greater than 150 pg/mL (ng/L), 2 consecutive serum calcium levels between 8.0 and 10.0 mg/dL (2.00 and 2.50 mmol/L), and 2 consecutive serum phosphorus levels of 5.2 mg/dL or less (< or = 1.68 mmol/L). Two studies used a thrice-weekly dosing regimen and 1 study used a once-daily dosing regimen for 24 weeks. Dosing was based on serum iPTH, calcium, and phosphorus levels. The primary efficacy end point is 2 consecutive decreases in iPTH levels greater than 30% from baseline.
                Two hundred twenty patients participated (n = 107, paricalcitol; n = 113, placebo). At least 2 consecutive decreases in iPTH levels of 30% or greater from baseline occurred in 91% of paricalcitol versus 13% of placebo patients (P < 0.001). Incidences of hypercalcemia, hyperphosphatemia, and elevated calcium-phosphorus product levels were not significantly different between groups. Similarly, no significant differences in urinary calcium and phosphorus excretion or deterioration in kidney function were detected in patients administered paricalcitol compared with placebo.
                Paricalcitol capsule was well tolerated and effectively decreased iPTH levels with minimal or no impact on calcium levels, phosphorus balance, and kidney function in patients with stages 3 and 4 CKD. Calcium carbonate has been successfully used as a phosphate binder in patients with chronic renal failure; however, a high frequency of hypercalcaemia has been reported. To study the effects of calcium carbonate preparations with different dissolution characteristics on the incidence of this side effect, we conducted a double-blind, crossover trial in 21 patients undergoing chronic haemodialysis. Aluminum hydroxide therapy was replaced with calcium carbonate. The subjects then randomly received either an enteric-coated or a gastric-coated preparation. Calcium carbonate (3.1-3.6 g/d) controlled serum phosphate concentrations as effectively as aluminium hydroxide (2.9 g/d). Concurrently, there was a significant rise in mean serum calcium and a fall in serum concentrations of both parathyroid hormone and osteocalcin, the latter suggesting a decrease in bone turnover. Overall, hypercalcaemic episodes developed in 9 patients (43%) and occurred at a considerable frequency (33 episodes per 100 patient-months) during treatment with the gastric-coated formulation. Following conversion to enteric-coated calcium carbonate (3.6 g/d) patients had fewer occurrences of hypercalcaemia (12 episodes per 100 patient-months, P less than 0.05) and, as compared to the gastric-coated preparation, increases in serum calcium greater than 3.00 mmol/l were not observed at all. Hyperaluminaemia was regressive during therapy with calcium carbonate, but addition of small doses of aluminium hydroxide caused a large rise in serum aluminium concentrations after infusion of desferrioxamine, indicating an enhanced rate of absorption or aberrant compartmentalization of aluminium. We conclude that calcium carbonate can control hyperphosphataemia in dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS) The aim of this crossover study was to compare the reduction of serum phosphorus (SP) with fixed doses of the non-calcium-containing phosphate binders lanthanum carbonate (LC) and sevelamer hydrochloride (SH) in hemodialysis patients.
                Following washout (2 - 3 weeks), 182 patients with SP >or= 6.0 mg/dl and calcium >or= 8.4 mg/dl were randomized (1:1) to receive LC (2,250 to 3,000 mg/day) or SH (4,800 to 6,400 mg/day) for 4 weeks. Patients underwent a second washout (2 weeks) and switched to the alternative binder for 4 weeks.
                At the end of treatment, LC had reduced SP by 1.7 +/- 0.1 mg/dl, compared with 1.4 +/- 0.1 mg/dl for SH; the difference was not statistically significant in the primary analysis (LOCF, p = 0.133). However, the reduction with LC was significantly greater than with SH in a prespecified key secondary analysis of patients who completed 4 weeks of treatment with each binder (0.5 mg/dl difference, p = 0.007). The reduction of SP was also greater with LC than SH after 1 week of treatment (p = 0.024).
                Although the primary analysis found no difference between LC and SH in the reduction of SP, a significant difference in favor of LC was observed in patients who completed treatment. The results of this study show interesting trends with respect to onset and duration of action that warrant further investigation in longer-term studies. Hyperphosphatemia has an important role in the development of bone and mineral abnormalities in end-stage renal disease (ESRD).
                To compare the phosphorus binding power and the hypercalcemic effect of calcium acetate and calcium carbonate in hemodialysis patients.
                Crossover, randomized, double-blind study.
                A private hospital dialysis center.
                Fifty-two patients who were undergoing regular hemodialysis three times a week ([Ca++] dialysate = 3.5 mEq/L).
                Half of the patients were started on 5.6 g/day of calcium acetate and, after a 2 week washout period, received 6.2 g/day of calcium carbonate. The other half followed an inverse protocol.
                Clinical interviews were conducted 3 times a week to monitor for side effects. Determinations of serum urea, calcium, phosphorus, hematocrit, Kt/V and blood gas analysis were obtained before and after each treatment.
                Twenty-three patients completed the study. A significant increase in calcium plasma levels was only observed after treatment with calcium carbonate [9.34 mg/dl (SD 0.91) vs. 9.91 mg/dl (SD 0.79), P < 0.01]. The drop in phosphorus levels was substantial and significant for both salts [5.64 mg/dl (SD 1.54) vs. 4.60 mg/dl (SD 1.32), P < 0.01 and 5.89 mg/dl (SD 1.71) vs. 4.56 mg/dl (SD 1.57), P < 0.01, for calcium acetate and calcium carbonate respectively]. The percentage reduction in serum phosphorus (at the end of the study) per milliequivalent of salt administered per day tended to be higher with calcium acetate but statistical significance was not found.
                Calcium acetate can be a good alternative to calcium carbonate in the handling of hyperphosphatemia in ESRD patients. When calcium acetate is used, control of hyperphosphatemia can be achieved with a lower administration of calcium, perhaps with a lower risk of hypercalcemia. Prevention of secondary hyperparathyroidism in uremia necessitates correction of hyperphosphatemia and hypocalcemia. In order to avoid aluminum toxicity, calcium containing phosphate binders are used increasingly, instead of aluminium hydroxide. Recent studies have shown that calcium acetate has many characteristics of an ideal phosphate binder. It is, for instance, a more readily soluble salt compared with calcium carbonate. This advantage might, however, disappear if calcium carbonate is taken on an empty stomach, a few minutes before meals. We examined the efficacy of three different phosphate binding agents in a randomized prospective study of 53 patients on regular hemodialysis. Bicarbonate dialyses were performed with a dialysate calcium concentration of 1.75 mmol/l. After a three-week wash-out period, patients received either aluminum hydroxide (control group), calcium acetate, or calcium carbonate as their phosphate binder. Patients were instructed to take the calcium salts a few minutes before meals on an empty stomach, and aluminum hydroxide during meals. Serum calcium, phosphate, intact parathormone, and alkaline phosphatase levels were determined every month. Patient compliance was estimated every month by asking the patients which phosphate binder and what daily dose they had used.
                Aluminum hydroxide tended to be the most effective phosphate binder. The mean +/- SEM required daily dose of calcium acetate at 12 months was 5.04 +/- 0.60 g, corresponding to 10.1 +/- 1.20 tablets of 500 mg. Co-medication with aluminum hydroxide, however, was needed (1.29 +/- 0.54 g per day, corresponding to 2.6 +/- 1.08 tablets of 500 mg). The required daily calcium carbonate dose appeared to be 2.71 +/- 0.48 g, corresponding to 5.4 +/- 0.95 capsules of 500 mg, with an adjuvant daily aluminum hydroxide dose of 0.69 +/- 0.27 g, corresponding to 1.4 +/- 0.55 tablets of 500 mg (p = 0.0055). Thus, the mean daily doses of elemental calcium were comparable between the calcium acetate and calcium carbonate-treated patients (1.28 +/- 0.15 g versus 1.09 +/- 0.19 g; n.s.). The incidence of hypercalcemic episodes (albumin-corrected serum calcium levels above 2.80 mmol/l) in the calcium acetate-treated group was 18% versus 31% in the calcium carbonate-treated group (p < 0.005). None of the aluminum hydroxide-treated patients experienced hypercalcemic episodes. Mean serum concentrations of alkaline phosphatase, intact parathormone, and aluminum did not differ between the groups.
                In chronic intermittent hemodialysis patients, per gram administered elemental calcium phosphate binding with either calcium acetate or calcium carbonate is equivalent, provided that calcium carbonate is taken on an empty stomach a few minutes before meals. The number of capsules calcium carbonate, but also the total amount in grams, necessary to keep serum phosphate and intact parathormone levels into an acceptable range then is significantly less. This might improve patient compliance. High serum phosphorus levels are a common problem in patients receiving long-term dialysis treatment. Lanthanum carbonate (Fosrenol) is a new non-aluminum, non-calcium phosphate binder developed for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). We report data from a recent trial, which, for the first time, assessed the efficacy and tolerability of lanthanum carbonate treatment, compared with placebo, in Chinese patients with ESRD.
                Following a one- to three-week washout phase and a four-week, open-label lanthanum carbonate dose-titration phase, male and female hemodialysis patients were randomized (1:1) to receive either lanthanum carbonate or placebo for four weeks. The primary efficacy parameter of the study was the control of serum phosphorus levels (< or =1.8 mmol/l [< or = 5.6 mg/dl]). Secondary endpoints included the profile of serum phosphorus during titration and parathyroid hormone, calcium, and calcium x phosphorus (Ca x P) product levels. The safety and tolerability of lanthanum carbonate were assessed by monitoring adverse events throughout the study.
                Mean serum phosphorus level at the end of washout was 2.5 +/- 0.5 mmol/l (7.7 +/- 1.5 mg/dl; n=73), and there was no evidence of a difference in levels between the treatment groups pre-randomization. At the end of the study, lanthanum carbonate-treated patients had significantly lower phosphorus levels (1.6 +/- 0.5 mmol/l [5.1 +/- 1.5 mg/dl]; n=30) than those receiving placebo (2.3 +/- 0.4 mmol/l [7.2 +/- 1.3 mg/dl]; n=31; p < 0.001). In addition, a significantly higher proportion of patients receiving lanthanum carbonate had controlled serum phosphorus levels (60%) compared with the placebo group (10%; p < 0.001). Ca x P product levels were also significantly lower in the lanthanum carbonate group at the end of randomized treatment (p < 0.001). Lanthanum carbonate was well tolerated; only one serious adverse event was reported, which was unrelated to treatment.
                Lanthanum carbonate was shown to be an effective and well-tolerated phosphate binder for the treatment of hyperphosphatemia in Chinese patients with ESRD. This finding supports the results of previous US and European studies, which have also shown that lanthanum carbonate treatment effectively controls serum phosphorus levels. Calcitriol lowers parathyroid hormone (PTH) levels in patients with chronic kidney disease (CKD) stages 3 and 4, but its use is limited by a low therapeutic index and concerns regarding hypercalcemia and acceleration of kidney disease. We evaluated doxercalciferol (1alpha-hydroxyvitamin D2) as an alternative therapy in a randomized, double-blinded, placebo-controlled, multicenter trial.
                Fifty-five adults with stage 3 or 4 CKD and an intact PTH (iPTH) level greater than 85 pg/mL (ng/L) completed 8 baseline weeks, followed by 24 weeks of oral therapy with doxercalciferol or placebo. Pretreatment demographics and biochemical features did not differ between groups. Dosages were increased gradually if iPTH level was not decreased by 30% or greater and serum calcium and phosphorus levels were stable. Regular monitoring included plasma iPTH, serum calcium and phosphorus, urinary calcium, bone-specific serum markers, and serum lalpha,25-dihydroxyvitamin D levels. Glomerular filtration rate (GFR) was measured before and after treatment.
                Mean plasma iPTH level decreased by 46% from baseline after 24 weeks of doxercalciferol treatment (P <0.001), but was unchanged with placebo. After 6 weeks, iPTH level reductions with doxercalciferol treatment exceeded those with placebo at all subsequent intervals (P <0.001). No clinically significant differences in mean serum calcium or phosphorus or urinary calcium levels or incidence of hypercalcemia, hyperphosphatemia, or hypercalciuria were noted between groups. Serum C- and N-telopeptide and bone-specific alkaline phosphatase levels decreased with doxercalciferol treatment relative to both baseline and placebo (P <0.01). Adverse-event rates and changes in GFR did not differ between groups.
                Doxercalciferol is safe and effective in controlling secondary hyperparathyroidism of patients with CKD stages 3 and 4. We conducted a randomized unblinded parallel clinical trial to compare the effectiveness, side effects and tolerance between calcium acetate (CA) and calcium carbonate (CC) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus (P) levels with aluminum hydroxide (AH). All patients were dialyzed against the same calcium dialyzate (1.62 mmol/l). The serum analytical tests included: calcium corrected to total protein, P, PTH (intact molecule) and bicarbonate. The study was divided into the following periods: P0: baseline measurements; P1: washout (withdrawal of AH for 15 days); P2: random allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium, stratified according to previous doses of AH (2 months); P3: adjustment of doses until control P (2 months). CA was poorly tolerated in 7 patients and CC in 2 (NS). The changes in serum P levels between P0 and P2 periods were lower in the CA group (1.73 +/- 0.25 vs. 1.80 +/- 0.50 mmol/l; p = 0.26) than in the CC group (1.77 +/- 0.35 vs. 1.93 +/- 0.48 mmol/l; p = 0.03, paired t test). Serum calcium was hardly modified by CA (2.42 +/- 0.20 vs. 2.47 +/- 0.17 mmol/l; NS) while in the CC group, it rose significantly (2.40 +/- 0.12 vs. 2.55 +/- 0.22 mmol/l; p = 0.0004). There were no differences in the control of PTH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)
Available phosphate-binding agents have been shown to reduce phosphorus levels in comparison to placebo. However, there are insufficient data to establish the comparative superiority of novel non-calcium binding agents over calcium-containing phosphate binders for patient-level outcomes such as all-cause mortality and cardiovascular end-points in CKD.