***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND 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 . METHODS Seventy-eight hemodialysis patients with secondary hyperparathyroidism were enrolled into this 18-week , double-blind , r and omized , 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 . RESULTS 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 . CONCLUSIONS The calcimimetic AMG 073 decreases both PTH and calcium x phosphorus levels in hemodialysis patients with secondary hyperparathyroidism Management of secondary hyperparathyroidism is challenging with traditional therapy . The calcimimetic cinacalcet HCl acts on the calcium-sensing receptor to increase its sensitivity to calcium , thereby reducing parathyroid hormone ( PTH ) secretion . This phase 3 , multicenter , r and omized , placebo-controlled , double-blind study evaluated the efficacy and safety of cinacalcet in hemodialysis ( HD ) and peritoneal dialysis ( PD ) patients with PTH > or = 300 pg/ml despite traditional therapy . A total of 395 patients received once-daily oral cinacalcet ( 260 HD , 34 PD ) or placebo ( 89 HD , 12 PD ) titrated from 30 to 180 mg to achieve a target intact PTH ( iPTH ) level of < or = 250 pg/ml . During a 10-wk efficacy assessment phase , cinacalcet was more effective than control for PTH reduction outcomes , including proportion of patients with mean iPTH levels < or = 300 pg/ml ( 46 versus 9 % ) , proportion of patients with > or = 30 % reduction in iPTH from baseline ( 65 versus 13 % ) , and proportion of patients with > or = 20 , > or = 40 , or > or = 50 % reduction from baseline . Cinacalcet had comparable efficacy in HD and PD patients ; 50 % of PD patients achieved a mean iPTH < or = 300 pg/ml . Cinacalcet also significantly reduced serum calcium , phosphorus , and Ca x P levels compared with control treatment . The most common side effects , nausea and vomiting , were usually mild to moderate in severity and transient . Once-daily oral cinacalcet was effective in rapidly and safely reducing PTH , Ca x P , calcium , and phosphorus levels in patients who received HD or PD . Cinacalcet offers a new therapeutic option for controlling secondary hyperparathyroidism in patients with chronic kidney disease on dialysis BACKGROUND The calcimimetic agent R-568 lowers plasma parathyroid hormone ( PTH ) levels in hemodialysis patients with mild secondary hyperparathyroidism , but its efficacy in those with more severe secondary hyperparathyroidism has not been studied . METHODS Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were r and omly assigned to 15 days of treatment with either 100 mg of R-568 ( N = 16 ) or placebo ( N = 5 ) . Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1 , 2 , 3 , 5 , 8 , 11 , 12 , and 15 . RESULTS Pretreatment PTH levels were 599 + /- 105 ( mean + /- SE ) and 600 + /- 90 pg/mL in subjects given R-568 or placebo , respectively , and values on the first day of treatment did not change in those given placebo . In contrast , PTH levels fell by 66 + /- 5 % , 78 + /- 3 % , and 70 + /- 3 % at one , two , and four hours , respectively , after initial doses of R-568 , remaining below pretreatment values for 24 hours . Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo . Despite lower ionized calcium concentrations on both the second and third days of treatment , predose PTH levels were 422 + /- 70 and 443 + /- 105 pg/mL , respectively , in patients given R-568 , and values fell each day by more than 50 % two hours after drug administration . Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study . Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568 , whereas values were unchanged in those given placebo .  Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568 ; five patients withdrew from study after developing symptoms of hypocalcemia , whereas three completed treatment after the dose of R-568 was reduced . CONCLUSIONS The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease BACKGROUND AND OBJECTIVES Patients with chronic kidney disease ( CKD ) receiving dialysis often develop secondary hyperparathyroidism with disturbed calcium and phosphorus metabolism . The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative ( KDOQI ) was established to guide treatment practice s for these disorders . The ACHIEVE study was design ed to test two treatment strategies for achieving KDOQI goals . DESIGN , SETTING , PARTICIPANTS , MEASUREMENTS Individuals on hemodialysis treated with vitamin D sterols were enrolled in this 33-week study . Subjects were r and omly assigned to treatment with either cinacalcet and low-dose vitamin D ( Cinacalcet-D ) or flexible vitamin D alone ( Flex-D ) to achieve KDOQI-recommended bone mineral targets . ACHIEVE included a 6-week screening phase , including vitamin D washout , a 16-week dose-titration phase , and an 11-week assessment phase . RESULTS Of 173 subjects enrolled , 83 % of Cinacalcet-D and 67 % of Flex-D subjects completed the study . A greater proportion of Cinacalcet-D versus Flex-D subjects had a > 30 % reduction in parathyroid hormone ( PTH ) ( 68 % versus 36 % , P < 0.001 ) as well as PTH < 300 pg/ml ( 44 % versus 23 % , P = 0.006 ) . The proportion of subjects simultaneously achieving targets for intact PTH ( 150 - 300 pg/ml ) and calcium-phosphorus product ( Ca x P ) ( < 55 mg2/dl2 ) was also greater ( 21 % versus 14 % ) , but this was not statistically significant . This was attributable to 19 % of Cinacalcet-D subjects with a PTH value below the KDOQI target range . CONCLUSIONS Achievement of KDOQI targets was difficult , especially with Flex-D. Maintaining calcium and phosphorus target values precluded the use of vitamin D doses necessary to lower PTH to within the narrow target range and highlighted limitations inherent to the KDOQI treatment algorithm Hyperphosphatemia is highly prevalent among patients with end-stage renal disease ( ESRD ) and is associated with increased mortality risk in hemodialysis ( HD ) patients . The mechanism through which this mortality risk is mediated is unclear . Data from two national r and om sample s of HD patients ( n = 12,833 ) was used to test the hypothesis that elevated serum PO(4 ) contributes mainly to cardiac causes of death . During a 2-yr follow-up , the cause-specific relative risk ( RR ) of death for patients was analyzed separately for several categories of cause of death , including coronary artery disease ( CAD ) , sudden death , and other cardiac causes , cerebrovascular and infection . Cox regression models were fit for each of the eight cause of death categories , adjusting for patient demographics and non-cardiovascular comorbid conditions . Time at risk for each cause-specific model was censored at death that result ed from any of the other causes . Higher mortality risk was seen for patients in the high PO(4 ) group ( > 6.5mg/dl ) compared with the lower PO(4 ) group ( < or = 6.5mg/dl ) for death result ing from CAD ( RR 1.41 ; P < 0.0005 ) , sudden death ( RR 1.20 ; P < 0.01 ) , infection ( RR 1.20 ; P < 0.05 ) , and unknown causes ( RR 1.25 ; P < 0.05 ) . Patients in the high PO(4 ) group also had non-significantly increased RR of death from other cardiac and cerebrovascular causes of death . The RR of sudden death was also strongly associated with elevated Ca x PO(4 ) product ( RR 1.07 per 10 mg(2)/dl(2 ) ; P < 0.005 ) and serum parathyroid hormone levels greater than 495 pg/ml ( RR 1.25 ; P < 0.05 ) . This study identifies strong relationships between elevated serum PO(4 ) , Ca x PO(4 ) product , and parathyroid hormone and cardiac causes of death in HD patients , especially deaths result ing from CAD and sudden death . More vigorous measures to reduce the prevalence of these factors in HD patients may result in improved survival AIMS This 1-year double-blind , placebo-controlled , multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis . METHOD Patients were r and omly assigned in a 1:1 ratio to cinacalcet or control treatment groups . The initial dose of cinacalcet ( or matching placebo ) was 30 mg . Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone ( iPTH ) response and safety profile . Sequential doses included 30 , 60 , 90 , 120 and 180 mg/d . Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus . Efficacy and safety were compared between treatment groups among patients who completed the study ( 52 total weeks of treatment ) . Reasons for withdrawal are presented for patients who did not complete the study . RESULTS A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet ( n = 99 ) or placebo ( n = 111 ) . Over the last 6 months of the study , a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level < or = 250 pg/ml ( 61.6 vs. 9.9 % , p < 0.001 ) or a > or = 30 % decrease in iPTH from baseline ( 81.8 vs. 21.6 % , p < 0.001 ) . Mean iPTH levels decreased by -47.8 % in the cinacalcet group and increased by + 12.9 % in the control group . Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following : serum calcium -6.5 vs. + 0.9 % ( p < 0.001 ) , serum phosphorus -3.6 vs. -1.1 % ( p = 0.465 ) , and Ca x P -9.9 vs. -0.3 % ( p = 0.006 ) . The most commonly reported adverse events related to study drug by the investigators included nausea ( 13 % cinacalcet , 5 % control ) , investigator-reported hypocalcemia ( 11 % cinacalcet , 1 % control ) , vomiting ( 9 % cinacalcet , 2 % control ) , dyspepsia ( 
    Output:
    
Calcimimetic treatment of SHPT leads to significant improvements in biochemical parameters that observational studies have shown to be associated with increased mortality , cardiovascular risk and osteitis fibrosa , but patient-based benefits have not yet been demonstrated in trials .