***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 AND OBJECTIVES Circulating fibroblast growth factor 23 ( FGF23 ) is associated with adverse cardiovascular outcomes in CKD . Whether FGF23 predicts cardiovascular mortality  after kidney transplantation , independent of measures of mineral metabolism and cardiovascular risk factors , is unknown . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The association between plasma C-terminal FGF23 and cardiovascular mortality was analyzed in a single-center prospect i ve cohort of 593 stable kidney transplant recipients ( mean age ± SD , 52 ± 12 years ; 54 % male ; estimated GFR , 47 ± 16 ml/min per 1.73 m(2 ) ) , at a median of 6.1 ( interquartile range , 2.7 - 11.7 ) years after transplantation . Multivariate Cox regression models were built , adjusting for measures of renal function and mineral metabolism ; Framingham risk factors ; the left ventricular wall strain markers midregional fragment of pro-A-type natriuretic peptide ( MR-proANP ) and N-terminal-pro brain natriuretic peptide ( NT-proBNP ) ; and copeptin , the stable C-terminal portion of the precursor of vasopressin . RESULTS In multivariate linear regression analysis , MR-proANP ( β=0.20 , P<0.001 ) , NT-proBNP ( β=0.18 , P<0.001 ) , and copeptin ( β=0.26 , P<0.001 ) were independently associated with FGF23 . During follow-up for 7.0 ( interquartile range , 6.2 - 7.5 ) years , 128 patients ( 22 % ) died , of whom 66 ( 11 % ) died due to cardiovascular disease ; 54 ( 9 % ) had graft failure . FGF23 was associated with an higher risk of cardiovascular mortality in a fully adjusted multivariate Cox regression model ( hazard ratio [ HR ] , 1.88 [ 95 % confidence interval ( CI ) , 1.11 to 3.19 ] ; P=0.02 ) . FGF23 was also independently associated with all-cause mortality ( full model HR , 1.86 [ 95 % CI , 1.27 to 2.73 ] ; P=0.001 ) . Net reclassification improved for both cardiovascular mortality ( HR , 0.07 [ 95 % CI , 0.01 to 0.14 ] ; P<0.05 ) and all-cause mortality ( HR , 0.11 [ 95 % CI , 0.05 to 0.18 ] ; P<0.001 ) . CONCLUSIONS Plasma FGF23 is independently associated with  cardiovascular and all-cause mortality after kidney transplantation .  The association remained significant after adjustment for measures of mineral metabolism and cardiovascular risk factors Background / Aims Osteoprotegerin ( OPG ) and fetuin-A are vascular calcification regulators that may be related to high cardiovascular ( CV ) mortality in hemodialysis ( HD ) patients . We evaluated the relationship between  OPG , fetuin-A , and pulse wave velocity ( PWV ) , a marker of vascular stiffness , and determined whether OPG and fetuin-A were independent predictors of CV events in HD patients . Methods We conducted a prospect i ve observational study in 97 HD patients .  OPG and fetuin-A  were measured at baseline and arterial stiffness was evaluated by PWV . All patients were stratified into tertiles according to serum OPG levels . Results A significant trend was observed across increasing serum OPG concentration tertiles for age , HD duration , systolic blood pressure , cholesterol , triglycerides , and PWV . Multiple linear regression analysis revealed that diabetes ( β = 0.430 , p = 0.000 ) and  OPG  levels ( β = 0.308 , p = 0.003 ) were independently associated with PWV . The frequency of new CV events was significantly higher in the upper OPG tertiles compared with those in the lower OPG tertiles . In Cox proportional hazards analysis , upper tertiles of OPG levels were significantly associated with CV events ( hazard ratio = 4.536 , p = 0.011 ) . Conclusions Serum OPG , but not fetuin-A , levels were closely associated with increased vascular stiffness , and higher OPG levels may be independent predictors of new CV events in HD patients Background Disordered mineral metabolism is implicated in the pathogenesis of vascular calcification in hemodialysis ( HD ) patients .  Fibroblast growth factor 23 ( FGF-23 ) is the main regulator of phosphate metabolism . In this prospect i ve study , we aim ed to investigate the association of serum FGF-23 with progression of coronary artery calcification in HD patients . Methods Seventy-four HD patients ( 36 male/38 female , mean age : 52 ± 14 years ) were included .  Serum FGF-23 levels were measured by ELISA . Coronary artery calcification score ( CACS ) was measured twice with one year interval . Patients were grouped as progressive ( PG ) ( 36 patients -48 % ) and non-progressive ( NPG ) . Results Age , serum phosphorus , baseline and first year CACS were found to be significantly higher in the PG compared to NPG group . Serum FGF-23 levels were significantly higher in PG [ 155 ( 80–468 ) vs 147 ( 82–234 ) , p = 0.04 ] . Patients were divided into two groups according to baseline CACS ( low group , CACS ≤ 30 ; high group , CACS > 30 ) . Serum FGF-23 levels were significantly correlated with the progression of CACS ( ΔCACS ) in the low baseline CACS group ( r = 0.51 , p = 0.006 ) , but this association was not found in high baseline CACS group ( r = 0.11 , p = 0.44 ) . In logistic regression analysis for predicting the PG patients ; serum FGF-23 , phosphorus levels and baseline CACS were retained as significant factors in the model . Conclusions Serum FGF-23 was found to be related to progression of CACS independent of serum phosphorus levels . FGF-23 may play a major role in the progression of vascular calcification especially at the early stages of calcification process in HD patients Klotho is a single-pass transmembrane protein predominantly expressed in the kidney . The extracellular domain of Klotho is subject to ectodomain shedding and is released into the circulation as a soluble form . Soluble Klotho is also generated from alternative splicing of the Klotho gene . In mice , defects in Klotho expression lead to complex phenotypes resembling those observed in dialysis patients . However , the relationship between the level of serum soluble Klotho and overall survival in hemodialysis patients , who exhibit a state of Klotho deficiency , remains to be delineated . Here we prospect ively followed a cohort of 63 patients with a mean duration of chronic hemodialysis of 6.7 ± 5.4 years for a median of 65 months .  Serum soluble Klotho  was detectable in all patients ( median 371 pg/mL , interquartile range 309–449 ) . Patients with serum soluble Klotho levels below the lower quartile ( < 309 pg/mL ) had significantly higher cardiovascular and all-cause mortality rates . Furthermore , the higher all-cause mortality persisted even after adjustment for confounders ( hazard ratio 4.14 , confidence interval 1.29–13.48 ) . We conclude that there may be a threshold for the serum soluble Klotho level associated with a higher risk of mortality BACKGROUND In patients with chronic kidney disease , vascular calcification contributes to increased cardiovascular ( CV ) morbidity and mortality . CV risk remains high after successful renal transplantation . Osteoprotegerin ( OPG ) is a glycoprotein , involved in the regulation of the vascular calcification process . Previous studies have shown that elevated OPG is predictive of mortality in high-risk population s. The aim of this study was to investigate the prognostic value of OPG for graft function , CV events and all-cause death , in a large transplant cohort . METHODS  OPG  was measured at baseline in renal transplant recipients enrolled in the Assessment of Lescol in Renal Transplantation ( ALERT ) study , a r and omized  placebo-controlled  intervention study comparing fluvastatin and placebo . Patients were followed for 6.7 years with evaluation of pre-specified end points , graft loss , graft function , CV events and death . RESULTS  OPG was analysed in 1889 renal transplant recipients , with a mean value of 4.69 ± 1.85 pg/L.  The number of renal and CV events increased by quartiles of OPG . In the multivariate analysis , OPG in the fourth as compared to first quartile was an independent predictor of graft failure or doubling of serum creatinine [ hazard ratio ( HR ) 2.20 ( 1.56 - 3.11 ) , P < 0.001 ] , major CV events [ HR 2.40 ( 1.58 - 3.64 ) , P < 0.001 ] , cardiac mortality [ HR 2.80 ( 1.32 - 5.94 ) , P = 0.007 ] and all-cause mortality [ HR 2.31 ( 1.53 - 3.49 ) , P < 0.001 ] . CONCLUSION In a large cohort of kidney transplant patients with long-term follow-up , OPG was independently associated with renal events , CV events and mortality Background Vascular calcifications ( VCs ) are a cardiovascular risk factor in patients affected by chronic kidney disease and after kidney transplantation ( KTx ) . We evaluated the prevalence of VCs at the abdominal aortic site in  KTx patients at the time of transplantation and 1 year after KTx , exploring the possibly associated factors . Methods In 107 transplanted patients , the following parameters were evaluated at the first and twelfth month after KTx : the aortic calcification index ( ACI ) , fibroblast growth factor 23 , osteoprotegerin ( OPG ) , fetuin A , and clinical and biochemical parameters .  Patients were followed up for 2 years after KTx . Results At the time of KTx , 60 % of patients had some degree of VC ( ACI>0 ) , whereas 40 % had no VC . One year after KTx , VCs worsened in 26 % of patients , whereas in 74 % , VCs remained stable or improved . The progression of VC was observed almost exclusively in patients with a positive ACI score at the first month . At the multivariate analysis , serum calcium , OPG , and estimated glomerular filtration rate were the only variables independently associated with the progression of VC . Conclusions VCs at the aortic site are frequent in  KTx patients , and in a significant percentage of them , they tend to progress even in the short time . High levels of serum calcium and OPG are significantly associated with the progression of VCs . Whether these associations are based on a cause-effect relationship and their correction might impact on the calcification process could be ascertained by prospect i ve interventional studies Deranged calcium-phosphate metabolism contributes to the burden of morbidity and mortality in dialysis patients . This study aim ed to assess the association of the phosphaturic hormone fibroblast growth factor 23 ( FGF23 ) and soluble Klotho with all-cause mortality . We measured soluble Klotho and FGF23 levels at enrolment and two weeks later in 239 prevalent hemodialysis patients . The primary hypothesis was that low Klotho and high FGF23 are associated with increased mortality . The association between Klotho and atrial fibrillation ( AF ) at baseline was explored as secondary outcome . AF was defined as presence of paroxysmal , persistent or permanent AF . During a median follow-up of 924 days , 59 ( 25 % ) patients died from any cause . Lower Klotho levels were not associated with mortality in a multivariable adjusted analysis when examined either on a continuous scale ( HR 1.25 per SD increase , 95 % CI 0.84–1.86 ) or in tertiles , with tertile 1 as the reference category ( HR for tertile two 0.65 , 95 % CI 0.26–1.64 ; HR for tertile three 2.18 , 95 % CI 0.91–2.23 ) . Higher Klotho levels were associated with the absence of AF in a muItivariable logistic regression analysis ( OR 0.66 per SD increase , 95 % CI 0.41–1.00 ) . Higher FGF23 levels were associated with mortality risk in a multivariable adjusted analysis when examined either on a continuous scale ( HR 1.45 per SD increase , 95 % CI 1.05–1.99 ) or in tertiles , with the tertile 1 as the reference category ( HR for tertile two 
    Output:
    
Reported risk estimates of RANK lig and , OPN , Klotho protein and BMP‐7 were not suitable for pooling ; however , only Klotho protein was significantly related to mortality .
In hemodialysis patients , FGF23 is a predictor of all‐cause and cardiovascular mortality , whereas the predictive value of OPG is restricted to cardiovascular mortality .