***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 Treatment of secondary hyperparathyroidism ( SHPT ) with activated vitamin D analogues is associated with better survival in patients receiving dialysis . It is unclear whether such a benefit is present in patients with predialysis chronic kidney disease ( CKD ) . METHODS We examined the association of oral calcitriol treatment with mortality and the incidence of dialysis in 520 male US veterans ( mean [ SD ] age , 69.8 [ 10.3 ] years ; 23.5 % black ) with CKD stages 3 to 5 and not yet receiving dialysis ( mean [ SD ] estimated glomerular filtration rate , 30.8 [ 11.3 ] ) . Associations were examined by the Kaplan-Meier method and in Poisson regression models with adjustment for age , race , comorbidities , smoking , blood pressure , body mass index , use of phosphate binders , estimated glomerular filtration rate , proteinuria , white blood cell count , percentage of lymphocytes , and levels of parathyroid hormone , calcium , phosphorus , albumin , bicarbonate , and hemoglobin . RESULTS Two hundred fifty-eight of 520 subjects received treatment with calcitriol , 0.25 to 0.5 microg/d , for a median duration of 2.1 years ( range , 0.06 - 6.0 years ) . The incidence rate ratios for mortality and combined death and dialysis initiation were significantly lower in treated vs untreated patients ( P < .001 for both in the fully adjusted models ) . Treatment with calcitriol was associated with a trend toward a lower incidence of dialysis . These results were consistent across different subgroups . CONCLUSIONS Treatment with the activated vitamin D analogue calcitriol appears to be associated with significantly greater survival in patients with CKD not yet receiving dialysis . R and omized clinical trials are required to verify the causality of these associations and to examine whether similar associations are seen with different activated vitamin D analogues 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 This prospect i ve , r and omized , controlled trial compared the progression of vascular and cardiac valve calcification in 360 prevalent adult hemodialysis patients with secondary hyperparathyroidism treated with either cinacalcet plus low-dose vitamin D sterols or flexible doses of vitamin D sterols alone . METHODS Eligible subjects were on hemodialysis for ≥ 3 months with parathyroid hormone ( PTH ) > 300 pg/mL or PTH 150 - 300 pg/mL with calcium-phosphorus product > 50 mg(2)/dL(2 ) while receiving vitamin D.  All subjects received calcium-based phosphate binders  . Coronary artery calcification ( CAC ) and aorta and cardiac valve calcium scores were determined both by Agatston and volume scoring using multi-detector computed tomography . Subjects with Agatston CAC scores ≥ 30 were r and omized to cinacalcet ( 30- 180 mg/day ) plus low-dose calcitriol or vitamin D analog ( ≤ 2 μg paricalcitol equivalent/dialysis ) , or flexible vitamin D therapy . The primary end point was percentage change in Agatston CAC score from baseline to Week 52 . RESULTS Median ( P10 , P90 ) Agatston CAC scores increased 24 % ( -22 % , 119 % ) in the cinacalcet group and 31 % ( -9 % , 179 % ) in the flexible vitamin D group ( P = 0.073 ) . Corresponding changes in volume CAC scores were 22 % ( -12 % , 105 % ) and 30 % ( -6 % , 133 % ; P = 0.009 ) . Increases in calcification scores were consistently less in the aorta , aortic valve and mitral valve among subjects treated with cinacalcet plus low-dose vitamin D sterols , and the differences between groups were significant at the aortic valve . CONCLUSIONS In hemodialysis patients with moderate to severe secondary hyperparathyroidism  , cinacalcet plus low-dose vitamin D sterols may attenuate vascular and cardiac valve calcification 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 BACKGROUND Secondary hyperparathyroidism is observed in patients with early chronic kidney disease ( CKD ) . This study investigated the safety and efficacy of cinacalcet for secondary hyperparathyroidism in participants with CKD not receiving dialysis . STUDY DESIGN Double-blind , r and omized , 32-week , phase 3 study . SETTING & PARTICIPANTS 404 participants with stage 3 or 4 
    Output:
    
Cinacalcet reduces the need for parathyroidectomy in patients with CKD stage 5D , but does not appear to improve all-cause or cardiovascular mortality .
Additional trials in CKD stage 5D are unlikely to change our confidence in the treatment effects of cinacalcet in this population