a survey in china showed that the number of patients with chronic kidney disease , which gradually leads to end - stage renal disease ( esrd ) , was approximately 119.5 million . according to the chinese national renal data system ( cnrds ) ,
the united states renal data system ( usrds ) reported that the mortality rate in 2013 of hemodialysis patients was 172/1000 patient - years .
moreover , dialysis patients risk for fatal hospitalization increased three - fold compared with that of the reference population .
identifying the factors associated with death in maintenance hemodialysis ( mhd ) patients is vital .
some studies used baseline data of mhd patients to analyze their survival ; however , laboratory data characteristics were variable .
some studies report that hemodialysis patients who are expected to die have certain clinical and biochemical characteristics .
however , little is known on the state of dialysis patients preceding death , especially in our country .
hence , our study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period .
this study aimed to determine the characteristics of dying patients and the factors associated with death in mhd patients .
this study was approved by the ethics committee of the chinese people 's liberation army general hospital .
patients under mhd therapy in 16 blood purification centers from 12 provinces in china from january 2012 to december 2014 were selected .
inclusion criteria were as follows : age 20 years , receiving mhd therapy for at least 3 months , and with laboratory data , including blood pressure , kt / v , hemoglobin , serum albumin , serum calcium , and serum phosphate . based on survival status ,
the participants were divided into two groups : the survival group ( still alive on december 31 , 2014 ) and the death group ( died of any cause within the study period ) .
patients who were lost to follow - up for any reason began peritoneal dialysis , or received kidney transplant before december 31 , 2014 , were included in the survival group .
data , including sex , age , primary cause of esrd , dialysis duration , death cause , type of vascular access , dialysis time every week , and laboratory results , were collected retrospectively .
information on the type of vascular access and laboratory results was obtained from the latest hemodialysis records before the primary study endpoints of patient death , lost to follow - up , or the end of the study period .
the primary cause of esrd was categorized as primary glomerulonephritis ( pgn ) , diabetic nephropathy ( dn ) , hypertensive nephropathy ( htn ) , and other / unknown .
death causes were classified as cardiovascular events , cerebrovascular events , infection , sudden death of unknown reason , bleeding , cancer , and other / unknown .
dialysis duration was defined as the number of months between their first renal replacement therapy and a primary endpoint or completion of the study .
types of vascular access were arteriovenous fistula ( avf ) , tunneled cuffed catheter ( tcc ) , noncuffed catheter ( ncc ) , arteriovenous graft , and other / unknown .
data were expressed as mean  standard deviation ( sd ) or median ( interquartile range ) for continuous variables according to their distribution and as percentages for categorical variables . between - group comparison
was performed using the student 's t - test or kruskal - wallis test for continuous variables and chi - square test for categorical variables .
variables that affected all - cause mortality ( p < 0.05 ) in the univariate analysis were included in the multivariate logistic regression analysis model to determine factors associated with all - cause mortality .
all analyses were performed with statistical package for the social sciences software ( version 21.0 , spss inc . ,
this study was approved by the ethics committee of the chinese people 's liberation army general hospital .
patients under mhd therapy in 16 blood purification centers from 12 provinces in china from january 2012 to december 2014 were selected .
inclusion criteria were as follows : age 20 years , receiving mhd therapy for at least 3 months , and with laboratory data , including blood pressure , kt / v , hemoglobin , serum albumin , serum calcium , and serum phosphate . based on survival status ,
the participants were divided into two groups : the survival group ( still alive on december 31 , 2014 ) and the death group ( died of any cause within the study period ) .
patients who were lost to follow - up for any reason began peritoneal dialysis , or received kidney transplant before december 31 , 2014 , were included in the survival group .
data , including sex , age , primary cause of esrd , dialysis duration , death cause , type of vascular access , dialysis time every week , and laboratory results , were collected retrospectively .
information on the type of vascular access and laboratory results was obtained from the latest hemodialysis records before the primary study endpoints of patient death , lost to follow - up , or the end of the study period .
the primary cause of esrd was categorized as primary glomerulonephritis ( pgn ) , diabetic nephropathy ( dn ) , hypertensive nephropathy ( htn ) , and other / unknown .
death causes were classified as cardiovascular events , cerebrovascular events , infection , sudden death of unknown reason , bleeding , cancer , and other / unknown .
dialysis duration was defined as the number of months between their first renal replacement therapy and a primary endpoint or completion of the study .
types of vascular access were arteriovenous fistula ( avf ) , tunneled cuffed catheter ( tcc ) , noncuffed catheter ( ncc ) , arteriovenous graft , and other / unknown .
data were expressed as mean  standard deviation ( sd ) or median ( interquartile range ) for continuous variables according to their distribution and as percentages for categorical variables . between - group comparison
was performed using the student 's t - test or kruskal - wallis test for continuous variables and chi - square test for categorical variables .
variables that affected all - cause mortality ( p < 0.05 ) in the univariate analysis were included in the multivariate logistic regression analysis model to determine factors associated with all - cause mortality .
all analyses were performed with statistical package for the social sciences software ( version 21.0 , spss inc . ,
data from 4104 esrd patients from 16 centers were obtained ( 57.58% male ; age 59   years ) , among whom 620 patients were dead .
table 1 shows that among the 4104 patients , patients with pgn were the most common ( n = 1902 , 46.35% ) , followed by those with dn ( n = 788 , 19.20% ) and htn ( n = 460 , 11.21% ) .
characteristics of the studied cohort and comparison of the two groups values are presented as median ( iqr ) or n ( % ) .
pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; iqr : interquartile range .
the most common cause of death was cardiovascular events ( n = 235 , 37.90% ) , followed by cerebrovascular events ( n = 126 , 20.32% ) , infection ( n = 73 , 11.77% ) , sudden death of unknown reason ( n = 36 , 5.81% ) , bleeding ( n = 35 , 5.65% ) , cancer ( n = 17 , 2.74% ) , and other /
the studied group was divided into two groups based on their outcome : the death group ( n = 620 ) and the survival group ( n = 3484 ) .
the death group had 61.90% males , while the survival group had 46.31% males ( p = 0.013 ) .
the death group had a significantly higher median age than the survival group ( 68   years vs. 58   years ) .
the median dialysis duration ( 35   months vs. 34   months ) was not significantly different between the two groups .
however , the death group had less patients with 312 months of dialysis duration ( 15.97% vs. 21.33% ) but more patients with 2560 months of dialysis duration ( 39.19% vs. 30.86% ) .
the percentage of patients with pgn as the primary cause of esrd in the death group was lower than that in the survival group ( 31.13% vs. 49.05% , respectively ) , while the percentage of patients with dn ( 35.81% vs. 16.25% ) or htn ( 15.16% vs. 10.51% ) was significantly higher in the death group . compared with the survival group ,
the death group had a lower diastolic blood pressure , hemoglobin , serum albumin , serum calcium , serum phosphate , and kt / v .
univariate analysis identified several factors associated with mortality , including sex , age , cause of esrd , type of vascular access , dialysis time every week , diastolic blood pressure , hemoglobin , serum albumin , serum calcium , serum phosphate , and kt / v [ table 2 ] .
subsequently , two multivariate analysis models were built : one model consisted of all significant factors in the univariate analysis , while the other excluded laboratory examination . in the nonlaboratory examination model , sex , age , dialysis duration , cause of esrd , type of vascular access , and dialysis time every week
male sex ( odd ratio [ or ] 1.302 ; 95% confidence interval [ ci ] : 1.0801.571 ) , age ( or 1.042 ; 95% ci : 1.0351.049 ) , dn ( or 2.472 ; 95% ci : 1.9693.105 ) , htn ( or 1.629 ; 95% ci : 1.2242.169 ) , and dialysis with tcc ( or 1.640 ; 95% ci : 1.2442.161 ) were independent risk factors for mortality .
dialysis with ncc ( or 0.320 ; 95% ci : 0.1920.532 ) seemed to be associated with better outcome .
univariate analysis of factors associated with all - cause mortality ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; or : odds ratio ; ci : confidence interval .
multivariate analyses of factors associated with all - cause mortality unadjusted for laboratory examination ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; or : odds ratio ; ci : confidence interval .
table 4 shows the multivariate analyses of factors associated with all - cause mortality adjusted for laboratory examination .
these results show that , after adjustment for laboratory variables , male sex , age , and dn were still significantly associated with higher mortality , while dialysis with ncc was associated with lower mortality .
moreover , we observed that high hemoglobin ( or 0.974 ; 95% ci : 0.9670.981 ) , serum albumin ( or 0.939 ; 95% ci : 0.9150.963 ) , and serum calcium ( or 0.585 ; 95% ci : 0.3460.989 ) levels were protective factors associated with mortality .
multivariate analyses of factors associated with all - cause mortality adjusted for laboratory examination ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; or : odds ratio ; ci : confidence interval .
data from 4104 esrd patients from 16 centers were obtained ( 57.58% male ; age 59   years ) , among whom 620 patients were dead .
table 1 shows that among the 4104 patients , patients with pgn were the most common ( n = 1902 , 46.35% ) , followed by those with dn ( n = 788 , 19.20% ) and htn ( n = 460 , 11.21% ) .
characteristics of the studied cohort and comparison of the two groups values are presented as median ( iqr ) or n ( % ) .
pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; iqr : interquartile range .
the most common cause of death was cardiovascular events ( n = 235 , 37.90% ) , followed by cerebrovascular events ( n = 126 , 20.32% ) , infection ( n = 73 , 11.77% ) , sudden death of unknown reason ( n = 36 , 5.81% ) , bleeding ( n = 35 , 5.65% ) , cancer ( n = 17 , 2.74% ) , and other / unknown ( n = 98 , 15.81% ) .
the studied group was divided into two groups based on their outcome : the death group ( n = 620 ) and the survival group ( n = 3484 ) .
the death group had 61.90% males , while the survival group had 46.31% males ( p = 0.013 ) .
the death group had a significantly higher median age than the survival group ( 68   years vs. 58   years ) .
the median dialysis duration ( 35   months vs. 34   months ) was not significantly different between the two groups .
however , the death group had less patients with 312 months of dialysis duration ( 15.97% vs. 21.33% ) but more patients with 2560 months of dialysis duration ( 39.19% vs. 30.86% ) .
the percentage of patients with pgn as the primary cause of esrd in the death group was lower than that in the survival group ( 31.13% vs. 49.05% , respectively ) , while the percentage of patients with dn ( 35.81% vs. 16.25% ) or htn ( 15.16% vs. 10.51% ) was significantly higher in the death group . compared with the survival group , the death group had a lower diastolic blood pressure , hemoglobin , serum albumin , serum calcium , serum phosphate , and kt / v .
univariate analysis identified several factors associated with mortality , including sex , age , cause of esrd , type of vascular access , dialysis time every week , diastolic blood pressure , hemoglobin , serum albumin , serum calcium , serum phosphate , and kt / v [ table 2 ] .
subsequently , two multivariate analysis models were built : one model consisted of all significant factors in the univariate analysis , while the other excluded laboratory examination . in the nonlaboratory examination model , sex , age , dialysis duration , cause of esrd , type of vascular access , and dialysis time every week were included .
male sex ( odd ratio [ or ] 1.302 ; 95% confidence interval [ ci ] : 1.0801.571 ) , age ( or 1.042 ; 95% ci : 1.0351.049 ) , dn ( or 2.472 ; 95% ci : 1.9693.105 ) , htn ( or 1.629 ; 95% ci : 1.2242.169 ) , and dialysis with tcc ( or 1.640 ; 95% ci : 1.2442.161 ) were independent risk factors for mortality .
dialysis with ncc ( or 0.320 ; 95% ci : 0.1920.532 ) seemed to be associated with better outcome .
univariate analysis of factors associated with all - cause mortality ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; or : odds ratio ; ci : confidence interval .
multivariate analyses of factors associated with all - cause mortality unadjusted for laboratory examination ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; esrd : end - stage renal disease ; or : odds ratio ; ci : confidence interval .
table 4 shows the multivariate analyses of factors associated with all - cause mortality adjusted for laboratory examination .
these results show that , after adjustment for laboratory variables , male sex , age , and dn were still significantly associated with higher mortality , while dialysis with ncc was associated with lower mortality .
moreover , we observed that high hemoglobin ( or 0.974 ; 95% ci : 0.9670.981 ) , serum albumin ( or 0.939 ; 95% ci : 0.9150.963 ) , and serum calcium ( or 0.585 ; 95% ci : 0.3460.989 ) levels were protective factors associated with mortality .
multivariate analyses of factors associated with all - cause mortality adjusted for laboratory examination ( n = 4104 ) pgn : primary glomerulonephritis ; dn : diabetic nephropathy ; htn : hypertensive nephropathy ; avf : arteriovenous fistula ; tcc : tunnelled cuffed catheter ; ncc : noncuffed catheter ; avg : arteriovenous graft ; or : odds ratio ; ci : confidence interval .
there exists abundant literature on the risk factors for death in mhd patients , which are based on the baseline data obtained from those patients .
however , little is known about the clinical and laboratory parameters associated with the status of mhd patients preceding death , especially in our country . in this study
, we used the latest records , i.e. , before patient outcome identification or end of the study period , to find the characteristics and factors associated with death in mhd patients .
the results showed that the death group had more men and more patients with dn and htn .
moreover , patients in the group also had higher age and lower levels of diastolic blood pressure , hemoglobin , albumin , serum calcium , serum phosphate , and kt / v compared with survival group .
multivariate analysis showed that male sex , age , dn , and low hemoglobin , albumin , and serum calcium levels were associated with death in hemodialysis patients .
the logistic regression analysis showed that lower hemoglobin and serum albumin were associated with death .
the low levels of albumin and hemoglobin might be the result of both inflammatory and nutritional components .
nevertheless , they could also lead to undesirable outcomes . low hemoglobin level and erythropoiesis - stimulating agents could lead to cardiovascular events , fatigue , and even mortality , while low serum albumin level in dialysis patients was also known to be associated with malnutrition , inflammation , and all - cause and cardiovascular mortality .
the result was partly in accordance with the studies that have reported that mhd patients experienced a decrease in serum albumin level in their final stages of life .
numerous reports have demonstrated that a high level of serum calcium and phosphate could cause vascular calcification and even mortality .
however , our data showed that serum calcium and phosphate levels of patients in the death group were significantly lower than those of patients in the survival group .
moreover , the logistic regression analysis revealed that lower serum calcium was associated with death . low serum calcium level could be associated with the hypoalbuminemic status , which might partly explain the results in our study .
k / doqi and kdigo guidelines state that , because serum calcium is partly bound to serum albumin , total serum calcium decreases 0.8 mg / dl ( 0.2 mmol / l ) for every 1 g decrease in serum albumin below 4 g / dl ( 40 g / l ) . furthermore , the time before death course is frequently characterized by a loss of regulatory functions in numerous subsystems of dialysis patients ; hence , their system can not react properly to perturbations .
we also speculate that the poor diet of patients in their final stages of life might be a cause of the low serum levels of calcium and phosphate .
however , we could only provide the results and suggest the phenomena without being able to reason them .
further deep studies are needed to explain these mechanisms and their interactions . in our study , male was an independent risk factor for mortality , and this study showed that more men than women were undergoing hemodialysis treatment , which is consistent with our national hemodialysis registry data and the usrds . in our results , male sex was associated with a 1.437 times risk of death , which is also seen in other studies .
furthermore , the dialysis outcomes and practice patterns study ( dopps ) analyzed 206,374 patients receiving hemodialysis in 12 countries and found that the survival advantage of women over men in the general population was markedly diminished in hemodialysis patients .
the dopps study also found that the male - to - female mortality rate ratio in the general population varied from 1.5 to 2.6 for age groups under 75 years , while that in hemodialysis patients was close to 1 . in the general population ,
women have longer life expectancy than men , which could be related to a lower prevalence of cardiovascular risk factors and events in women .
in hemodialysis patients , men were younger , were less frequently obese , received kidney transplant more frequently , and were less frequently depressed .
these factors may partly explain the survival advantage of females in the general population and the lack of that survival advantage in females requiring hemodialysis . according to the cnrds , glomerulonephritis ( 54.2% ) was the most frequent disease among chinese hemodialysis patients in 2015 , followed by dn ( 17.0% ) and htn ( 9.9% ) . in our study ,
the leading cause of esrd in the survival group was similar to that in the annual data report of cnrds .
however , in the death group , dn ( n = 222 , 35.81% ) accounted for a larger proportion of deaths compared with gn ( n = 193 , 31.13% ) .
the death group also had a higher proportion of htn patients than that in the report of cnrds .
logistic regression analysis also showed that the risks of death in patients with dn or htn were 2.472 times and 1.629 times higher , respectively , than those of patients with pgn before adjusting for laboratory examination . after adjusting for laboratory examination , dn remained risk factors for death .
as reported , the incidence of hypertension , coronary heart disease , and cerebral thrombus in dn patients is higher than those in non - dn patients .
the absolute cardiovascular disease ( cvd ) risk in diabetic patients is two - fold greater than that in persons without diabetes .
conditions associated with diabetes mellitus type 2 , such as insulin resistance , hyperinsulinemia , and hyperglycemia , may lead to inflammation , dyslipidemia , endothelial dysfunction , and oxidative stress , which could predispose patients to atherosclerosis and cvd .
patients often used catheters when they initiated hemodialysis ; thus , the percentage of ncc use was higher at 312 months than at 1 year after dialysis initiation . in our study , compared with the death group ,
therefore , we hypothesize that this may explain the apparent advantage of ncc . in this study , we used logistic regression rather than the cox 's proportional hazard model .
we began the follow - up on january 1 , 2012 , rather than the time when patients began their first hemodialysis .
the survival time in this study should be calculated from the study entry date ( january 1 , 2012 ) to the date of death , lost to follow - up , or the end of the study ( december 31 , 2014 ) .
however , patients who started dialysis before the entry date had survived for a period of time , which should be included in their real survival time . those might affect the cox 's proportional hazard model analysis to some extent .
first , the laboratory data were obtained from the latest records before patient outcome identification .
second , there were no lipid profile , uric acid , and body mass index ( bmi ) data in the analysis , which might be associated with death in mhd patients . considering that not all the patients underwent the lipid profile or uric acid examination in this study
moreover , some hospitals did not record patients height or bmi in the hemodialysis record .
we , therefore , thought that the bmi data might not be accurate enough and did not include it .
third , as the data were collected retrospectively , information bias to some extent existed .
hence , our data do not reflect the overall mhd patients status in our country . in conclusion , this study revealed the characteristics of mhd patients prior to death and the factors associated with death in mhd patients .
hemodialysis patients preceding death had lower hemoglobin , albumin , and serum calcium levels but higher age .
multivariate analysis showed that male sex , age , dn , low hemoglobin , albumin , and serum calcium levels were associated with death in hemodialysis patients .
this study was supported by grants from the national key technology r&d program ( no .
2011bai10b08 ) ; special fund for nhfpc scientific researchin the public welfare ( no . 201502023 ) , the fund of chinese pla 12th five - year plan for medical sciences ( no.bws14j040 ; no .
this study was supported by grants from the national key technology r&d program ( no .
2011bai10b08 ) ; special fund for nhfpc scientific researchin the public welfare ( no . 201502023 ) , the fund of chinese pla 12th five - year plan for medical sciences ( no.bws14j040 ; no .
 background : patients on hemodialysis have a high - mortality risk . 
 this study analyzed factors associated with death in patients on maintenance hemodialysis ( mhd ) . while some studies used baseline data of mhd patients , this study used the most recent data obtained from patients just prior to either a primary endpoint or the end of the study period to find the characteristics of patients preceding death.methods:participants were selected from 16 blood purification centers in china from january 2012 to december 2014 . 
 patients data were collected retrospectively . based on survival status , 
 the participants were divided into two groups : survival group and the death group . 
 logistic regression analysis was performed to determine factors associated with all - cause mortality.results:in total , 4104 patients ( 57.58% male , median age 59 years ) were included . 
 compared with the survival group , the death group had more men and more patients with diabetic nephropathy ( dn ) and hypertensive nephropathy . 
 the patients preceding death also had lower levels of diastolic blood pressure , hemoglobin , serum albumin , serum calcium , serum phosphate , kt / v , and higher age . 
 multivariate analysis revealed that male sex ( odd ratio [ or ] : 1.437 , 95% confidence interval [ ci ] : 1.0941.886 ) , age ( or : 1.046 , 95% ci : 1.0361.057 ) , and presence of dn ( or : 1.837 , 95% ci : 1.3222.552 ) were the risk factors associated with mortality . 
 high serum calcium ( or : 0.585 , 95% ci : 0.3460.989 ) , hemoglobin ( or : 0.974 , 95% ci : 0.9670.981 ) , albumin ( or : 0.939 , 95% ci : 0.9150.963 ) levels , and dialysis with noncuffed catheter ( or : 0.165 , 95% ci : 0.0700.386 ) were protective factors based on a multivariate analysis.conclusions:hemodialysis patients preceding death had lower hemoglobin , albumin , and serum calcium levels . 
 multivariate analysis showed that male sex , age , dn , low hemoglobin , low albumin , and low serum calcium were associated with death in hemodialysis patients . 