***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: BACKGROUND JTT-751 is a novel phosphate binder containing ferric citrate as the active ingredient . METHODS In this Phase 3 , multicenter , r and omized , open-label , parallel-group study , we compared the efficacy and safety of JTT-751 and sevelamer hydrochloride in patients undergoing hemodialysis . A total of 230 patients with a serum phosphate ≥1.97 and < 3.23 mmol/L were r and omized to JTT-751 ( dose adjusted between 1.5 and 6.0 g/day ) or sevelamer hydrochloride ( dose adjusted between 3.0 and 9.0 g/day ) for 12 weeks . The primary outcome was change in serum phosphate from baseline to end of treatment . Secondary outcomes included the changes in corrected serum calcium and intact parathyroid hormone ( PTH ) . The changes in ferritin , transferrin saturation and erythropoiesis-stimulating agent dose were additional outcomes . RESULTS Changes in serum phosphate at the end of treatment were -0.82 mmol/L in the JTT-751 group and -0.78 mmol/L in the sevelamer group , establishing non-inferiority of JTT-751 compared with sevelamer ( least squares mean , -0.03 mmol/L ; 95 % confidence interval , -0.13 to 0.07 mmol/L ) . Corrected serum calcium increased and PTH decreased from baseline within both groups ; changes between groups were similar . Gastrointestinal disorders were the most common adverse events in both groups ; the incidence of diarrhea was higher in the JTT-751 group , while constipation occurred frequently in the sevelamer group . Treatment with JTT-751 result ed in significant relative increases in serum ferritin and transferrin saturation . CONCLUSIONS Efficacy and safety of JTT-751 was comparable to sevelamer in patients on hemodialysis with hyperphosphatemia . Differential adverse effects were observed ; biochemical markers of iron status increased in patients treated with JTT-751 . TRIAL REGISTRATION NUMBER CTI-111433 ( The Japan Pharmaceutical Information Center at : http//www . clinical trials.jp ) . Date of registration : 7 March 2011 BACKGROUND AND OBJECTIVES Higher phosphate is associated with mortality in dialysis patients but few prospect i ve studies assess this in nondialysis patients managed in an outpatient nephrology clinic . This prospect i ve longitudinal study examined whether phosphate level was associated with death in a referred population . DESIGN , SETTING , PARTICIPANTS & MEASUREMENTS Patients ( 1203 ) of nondialysis chronic kidney disease ( CKD ) in the Chronic Renal Insufficiency St and ards Implementation Study were assessed .  Survival analyses were performed for quartiles of baseline phosphate relative to GFR , 12-month time-averaged phosphate , and baseline phosphate according to published phosphate targets . RESULTS  Mean ( SD ) eGFR was 32 ( 15 ) ml/min per 1.73 m(2 ) , age 64 ( 14 ) years , and phosphate 1.2 ( 0.30 ) mmol/L. Cox multivariate adjusted regression in CKD stages 3 to 4 patients showed an increased risk of all-cause and cardiovascular mortality in the highest quartile compared with that in the lowest quartile of phosphate . No association was found in CKD stage 5 patients . Patients who had values above recommended targets for phosphate control had increased risk of all-cause and cardiovascular death compared with patients below target . The highest quartile compared with the lowest quartile of 12-month time-averaged phosphate was associated with an increased risk of mortality . CONCLUSIONS In CKD stages 3 to 4 patients , higher phosphate was associated with a stepwise increase in mortality . As phosphate levels below published targets ( as opposed to within them ) are associated with better survival , guidelines for phosphate in nondialysis CKD patients should be re-examined . Intervention trials are required to determine whether lowering phosphate will improve survival Background / Aims : JTT-751 ( ferric citrate hydrate ) is a novel oral , iron-based phosphate binder being developed for the treatment of hyperphosphatemia among chronic kidney disease patients who are on dialysis . This study investigated the dose-response and safety of JTT-751 among Japanese hemodialysis patients . Methods : This was a multicenter , r and omized , placebo-controlled , double-blind , parallel-group , comparative study . A total of 192 subjects with serum phosphorus ( P ) levels between 6.1 and 10.0 mg/dl were r and omized to JTT-751 ( 1.5 , 3 or 6 g/day ) or to placebo treatment for 28 days . Changes in serum P level from baseline were examined . Results : In the full analysis set , the mean change in serum P level at week 4 was 0.04 , –1.28 , –2.16 and –4.10 mg/dl in the placebo , 1.5-grams , 3-grams and 6-grams/day groups , respectively , demonstrating a dose-response relationship up to 6 g/day . Overall , a reduction in serum P levels to ≤5.5 mg/dl was achieved in 2.5 , 16.7 , 50.0 and 92.6 % of subjects , in the placebo , 1.5-grams , 3-grams and 6-grams/day groups , respectively . The most common adverse events ( AEs ) were gastrointestinal disorders . Most AEs were mild . In 25 patients , treatment was discontinued due to increased transferrin saturation ≥50 % ; however , this was not considered to be a safety issue . Conclusions : When hemodialysis subjects  received JTT-751 at doses between 1.5 and 6 g/day for 28 days , serum P levels were significantly reduced in a dose-dependent manner ( p < 0.001 ) . JTT-751 was found to be efficacious and safe , with the majority of subjects in the 6-grams/day group achieving a serum P level of ≤5.5 mg/dl Efficacy of PA21 ( sucroferric oxyhydroxide ) , a novel calcium-free polynuclear iron(III)-oxyhydroxide phosphate binder , was compared with that of sevelamer carbonate in an open-label , r and omized , active-controlled phase III study . Seven hundred and seven hemo- and peritoneal dialysis patients with hyperphosphatemia received PA21 1.0–3.0 g per day and 348 received sevelamer 4.8–14.4 g per day for an 8-week dose titration , followed by 4 weeks without dose change , and then 12 weeks maintenance . Serum phosphorus reductions at week 12 were −0.71 mmol/l ( PA21 ) and −0.79 mmol/l ( sevelamer ) , demonstrating non-inferiority of , on average , three tablets of PA21 vs. eight of sevelamer . Efficacy was maintained to week 24 . Non-adherence was 15.1 % ( PA21 ) vs. 21.3 % ( sevelamer ) . The percentage of patients that reported at least one treatment-emergent adverse event was 83.2 % with PA21 and 76.1 % with sevelamer . A higher proportion of patients withdrew owing to treatment-emergent adverse events with PA21 ( 15.7 % ) vs. sevelamer ( 6.6 % ) . Mild , transient diarrhea , discolored feces , and hyperphosphatemia were more frequent with PA21 ; nausea and constipation were more frequent with sevelamer . After 24 weeks , 99 hemodialysis patients on PA21 were re-r and omized into a 3-week superiority analysis of PA21 maintenance dose in 50 patients vs. low dose ( 250 mg per day ( ineffective control ) ) in 49 patients . The PA21 maintenance dose was superior to the low dose in maintaining serum phosphorus control . Thus , PA21 was effective in lowering serum phosphorus in dialysis patients , with similar efficacy to sevelamer carbonate , a lower pill burden , and better adherence BACKGROUND 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 . METHODS To extend this observation , we performed an open-label , r and om 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 r and omly 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 . RESULTS 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 . CONCLUSION 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 AIM Limitations of conventional phosphate binders have led to the development of novel non-calcium , non-aluminium agents for use in patients with chronic kidney disease ( CKD ) . The iron-based agent PA21 ( stabilized polynuclear iron(III)-oxyhydroxide ) has high phosphate binding capacity in vitro . This study was undertaken to investigate the uptake of iron after oral administration of PA21 in order to identify any potential risk of iron overload in the clinical setting , and to obtain a preliminary assessment of the effect of PA21 on serum phosphate levels prior to larger trials over a longer treatment period . MATERIAL S AND METHODS An open-label , Phase I study was undertaken in which PA21 10 g/day was administered for 7 days to 8 nondialysis-dependent CKD patients ( Stages 3 - 4 ) , 8 maintenance hemodialysis patients and 8 healthy subjects . In addition , a single dose of radiolabeled PA21 was administered to determine iron uptake . RESULTS Median iron uptake ( range ) was 0.06 % ( 0.008 - 0.44 % ) , 0.02 % ( 0 - 0.04 % ) and 0.43 % ( 0.16 % - 1.25 % ) in the nondialysis-dependent CKD patients , hemodialysis patients and healthy subjects , respectively . Serum phosphate level decreased over the 7-day treatment period in the nondialysis patients ( 1.44 + or - 0.29 mmol/l to 1.10 + or - 0.27 mmol/l , p < 0.01 ) and the hemodialysis patients ( 2.85 + or - 0.78 mmol/l to 2.25 + or - 0.85 mmol/ , p < 0.01 ) . The most common adverse event was diarrhea ( n = 9 ) ; all cases were mild to moderate . CONCLUSION Findings from this short-term study indicate that PA21 may be an efficacious and well-tolerated phosphate binder with low iron uptake that may offer a promising alternative to existing hyperphosphatemia therapies . These results will need to be confirmed with longer-term , controlled studies Background SBR759 , an iron (III)-based oral phosphate binder , was developed for the treatment of hyperphosphataemia in chronic kidney disease stage V patients receiving maintenance renal replacement therapy ( RRT ) . Serum phosphate-lowering efficacy and dose response of SBR759 ( 3- , 6- , 9- and 12-g/day doses ) were compared with placebo . 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CONCLUSION Iron-based phosphate binders are as effective as sevelamer and well tolerated for hyperphosphatemia in dialysis patients .
Iron-based phosphate binders appear to have a beneficial effect on renal anemia in patients receiving dialysis .
Therefore , iron-based phosphate binders may represent a new treatment option for dialysis patients