The vascular access (VA) used at hemodialysis (HD) inception is involved in the mortality risk. We analyzed the survival of incident patients over time according to the initial VA and the VA profile of patients who died during the first year of follow-up.
Data of VA were obtained from 9956 incident HD patients from the Catalan Registry.
Over 12 years, 47.9% of patients initiated HD with a fístula, 1.2% with a graft, 15.9% with a tunneled catheter and 35% with an untunneled catheter. Regarding fistula use, the hazard ratio of death for all-causes over time when applying a multivariate competing risk model was 1.55 [95% confidence interval (CI): 1.42-1.69] and 1.43 (95% CI: 1.33-1.54) for patients with tunneled and untunneled catheter, respectively. During the first year of follow-up, the crude all-cause mortality rate (deaths/100 patient-years) was higher during the early (first 120 days) compared to the late (121-365 days) period: 18.3 (95% CI: 16.8-19.8) versus 15.4 (95% CI: 14.5-16.5). Regarding fistula use, for patients using untunneled and tunneled catheter, the odds ratio of death in the early period for all-causes was 3.66 (95% CI: 2.80-4.81) and 2.97 (95% CI: 2.17-4.06), for cardiovascular causes it was 2.76 (95% CI: 1.90-4.01) and 1.84 (95% CI: 1.17-2.89) and for infection-related causes it was 6.62 (95% CI: 3.11-14.05) and 4.58 (95% CI: 2.00-10.52), respectively.
Half of all incident patients in Catalonia are exposed to excessive mortality risk related to catheter and this scenario can be improved by early fistula placement.
J Vasc Access 2016; 17(1): 20 - 28
Article Type: ORIGINAL RESEARCH ARTICLE
AuthorsRamon Roca-Tey, Emma Arcos, Jordi Comas, Higini Cao, Jaume Tort, and the Catalan Renal Registry Committee
- • Accepted on 03/08/2015
- • Available online on 08/09/2015
- • Published in print on 28/01/2016
This article is available as full text PDF.
Despite improvements achieved in both the healthcare of chronic kidney disease (CKD) patients and hemodialysis (HD) technology in recent years, the clinical outcomes of this treatment are still influenced by the vascular access (VA) type in use (1). It has been suggested that the VA type could be involved in the variability of current mortality observed between countries (2) or between dialysis techniques (peritoneal dialysis vs. HD) (3). In this regard, bearing in mind the existing biases (4), initiating HD treatment using a central venous catheter (CVC) has been associated with higher risk of death over time compared with a mature fístula (AVF) (5-6-7-8-9-10-11-12-13-13).
The highest all-cause mortality rate of incident HD patients occurs during the first year of treatment (14) and, more specifically, within the first 120 days (early period) compared to 121-365 days (late period) after starting HD (15-16-17). It has been reported that CVC use at the HD inception is one of the factors independently associated with the increased mortality risk during the first year of HD treatment (15, 16). However, is this mortality risk constant throughout the whole first year of follow-up (early and late periods) for both types of CVC? It’s necessary to identify the temporal profile of mortality associated with tunneled (TCC) and untunneled (UCC) central catheters and also clarify its specific weight on the mortality risk.
Using the data from the Catalan Registry, we performed a retrospective observational study to assess the survival of chronic HD patients over time according to the initial VA and to analyze the VA profile of incident patients who died during the first year of follow-up.
Materials and methods
The Catalan Renal Registry (RMRC)
The data source used for this study is the Registry of Catalonia, an autonomous community of Spain with a population of 7,553.197 million residents in 2011. This Registry collects data from 46 centers about HD initiation, changes of center and/or treatment modality, deaths and patient exclusion, as well as annual update of all active cases on the 31st of December of each year.
Patients and vascular accesses
We analyzed the VA of the incident HD patients from the 1st of January 2000 until December 31, 2011. We have included all patients resident in Catalonia aged 18 years or older with end-stage renal disease (ESRD) starting chronic HD program as their initial form of renal replacement treatment (RRT).
The following baseline variables were analyzed: gender, age, primary kidney disease, associated comorbidities (coronary artery disease, cardiomyopathy, cardiac conduction disorders, cerebrovascular disease, peripheral vascular disease, chronic respiratory disease and diabetes not considered as primary kidney disease) grouped according to the International Classification of Diseases (ICD-9) (18). The duration of nephrology care before HD start was also considered, as well as ESRD presentation form (acute presentation of CKD not previously known or acute-on-chronic renal disease or steady progression of known CKD) and period of HD initiation (2000-2005 or 2006-2011).
The causes of death were codified according to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) (19) codes and we have classified them into seven categories: unknown, cardiovascular, infection, liver or gastrointestinal disease, cancer, social (suicide, dialysis withdrawal) and miscellaneous.
The VA used at HD inception was classified as one of four types: AVF, arteriovenous graft (AVG), TCC and UCC. To assess the changes from the initial VA, we used the information collected in the two first annual follow-up reports at 31 December, in order to have at least one year follow-up in all cases. We determined the direction of changes comparing the initial VA with the VA used in the first and second follow-up at December 31.
Continuous and categorical variables were described as mean ± standard deviation and as percentages, respectively. We evaluated the differences between each type of VA and the variables studied using the analysis of variance and the chi-square test.
The risk of death for all-causes over time was obtained by means of a multivariate competing risk model where kidney transplantation, switch to peritoneal dialysis or renal function recovery acts as competing risk (20). This model was adjusted taking into account all potential confounding aforementioned baseline variables.
Considering the incident patients who died during the first year of follow-up, we describe the initial VA and the causes of death overall, during the first 120 days (early period) and during the period of 120-365 days (late period). For this purpose, although the patients considered for the study were those included until December 31, 2011, the observation period ended on December 31, 2012. The odds ratios (OR) for all-cause, cardiovascular- and infectious-related mortality during these periods, according to the initial VA type, were estimated using logistic regression models taking into account all the potential confounding variables previously outlined. We also analyzed the change in the adjusted all-cause mortality risk associated with the switch of the initial VA during the first year of follow-up. Patients starting HD with AVG and who died during the first year of follow-up were excluded from the final analysis of mortality because of the low number (n = 14).
Data analysis was performed using STATA software version 11.
During 2000-2011, 9956 patients met the inclusion criteria.
Characteristics of the incident hemodialysis patients according to the initial vascular access during the study period
|% Missing (n = 9956)||% UCC (3485)||% TCC (1582)||% AVF (4773)||% AVG (116)||p value*|
|AVF = arteriovenous fistula; AVG = arteriovenous graft; ESRD = end-stage renal disease; TCC = tunneled central vein catheter; UCC = untunneled central vein catheter.|
|0||Age group (years)||45-64||32.6||13.8||52.3||1.3|
|Primary Renal Disease (PRD)||Glomerular disease||36.7||13||49.2||1.1|
|Polycystic kidney disease||16.2||7.3||74.7||1.8|
|3.2||Duration of predialysis nephrology care (years)||<1||59.1||22.1||18.5||0.3||p<0.001|
|0.9||Coronary artery disease||No||34.6||14.8||49.5||1.1||p<0.001|
|0.9||Cardiac conduction disorders||No||33.8||15.3||49.7||1.2||p<0.001|
|1||Peripheral vascular disease||No||34.2||15.4||49.2||1.2||p<0.001|
|0.9||Chronic respiratory disease||No||33.9||15.4||49.5||1.2||p<0.001|
|0.8||Diabetes (not PRD)||No||34.8||15.2||48.7||1.3||p<0.001|
|2.1||ESRD presentation||Unknown chronic renal disease||70.4||22.3||7.2||0.1||p<0.001|
|Acute-on-chronic renal disease||53.6||20.4||25.4||0.6|
|0||Period of time||2000-2005||40.1||11.1||47.6||1.2||p<0.001|
Changes in the VA during the first year of follow-up
We were able to study a possible VA change in 6705 (67.3%) incident patients of whom there was available information about the VA in two consecutive follow-up reports at 31 December. Overall, 66.6% of these patients changed the initial VA during the first year of follow-up. This percentage was 90.1% and 81.7% in patients with UCC and TCC as first VA, respectively.
Regarding the direction of these VA changes, more than half of incident patients who started HD with UCC and TCC changed to an AVF during the first year of follow-up (67.2 and 59.6%, respectively). Despite having wide variability, the period of time necessary for AVF placement was significantly higher for patients who initiated HD by TCC (107.5 ± 212.9 days) in relation to that of UCC (85.8 ± 194.4 days) (p = 0.015).
Survival of patients according to the initial VA
We found significant differences in patient survival over time according to the VA used in the first HD performed. Regarding initiating HD with a mature AVF (reference), the adjusted hazard ratio (HR) of death was 1.55 [95% CI: 1.42-1.69, p<0.001], 1.43 (95% CI: 1.33-1.54, p<0.001) and 1.08 (95% CI: 0.84-1.38, p = 0.56) for the patients who started HD through TCC, UCC and AVG, respectively (
Cumulative incidence of dying over time according to the vascular access used in the first hemodialysis (HD) session. Multivariate competing risk regression model. Meaning of the curves from top to bottom: tunnelled central catheter (TCC), untunnelled central catheter (UCC), arteriovenous graft (AVG), arteriovenous fistula (AVF).
Characteristics of the incident HD patients who died during the first year of follow-up
Of the 4700 patients who died during the study period, 1481 (31.5%) patients died during the first year of follow-up reaching a crude mortality rate of 14.6 deaths/100 patient-years (95% CI: 14.2-15.9). When comparing these patients with the survivors after the first year of follow-up (n = 8475), we have observed significant differences in all variables analyzed excepting gender (
Characteristics of the patients who died and who survived during the first year of follow-up
|Death 1-365 days (n = 1481)||Survived >365 days (n = 8475)||p-value1|
|2 UCC = untunneled central vein catheter; TCC = tunneled central vein catheter; AVF = arteriovenous fistula; AVG = arteriovenous graft.|
|Age group (years)||18-44||31||2.1||884||10.4||<0.001|
|Primary renal disease (PRD)||Glomerular||118||8.0||1,087||12.8||<0.001|
|Duration of pre-dialysis nephrology care (years)||<1||527||36.6||2,168||26.5||<0.001|
|Initial comorbidity||Coronary artery disease||474||32.2||1,715||20.4||<0.001|
|Cardiac conduction disorders||453||30.9||1,321||15.7||<0.001|
|Peripheral vascular disease||500||34.1||1,757||20.9||<0.001|
|Chronic respiratory disease||413||28.1||1,487||17.7||<0.001|
|Diabetes (not PRD)||183||12.4||644||7.7||<0.001|
|End-stage renal disease presentation||Unknown chronic renal disease||230||15.7||790||9.5||<0.001|
|Acute-on-chronic renal disease||543||37.1||2,328||28.1|
|Period of hemodialysis inception||2000-2005||839||56.7||4,301||50.7||<0.001|
|First vascular access2||UCC||746||50.4||2,739||32.3||<0.001|
VA profile of incident HD patients who died during the first year of follow-up
Patients who died during the first year of follow-up showed a higher percentage of UCC (50.4% vs. 32.3%) and lower percentage of AVF (27.8% vs. 51.5%) compared with the survivors (for both comparisons, p<0.001) (
Classification of the patients who died and who survived during the first year of follow-up according to age group and type of initial vascular access
|Age group (years)||Type of initial vascular access||Death 1-365 days N (%)||Survived >365 days N (%)|
|UCC = untunneled central vein catheter; TCC = tunneled central vein catheter; AVF = arteriovenous fistula; AVG = arteriovenous graft.|
|18-44||UCC||20 (64.5)||349 (39.5)|
|TCC||8 (25.8)||125 (14.1)|
|AVF||3 (9.7)||405 (45.8)|
|AVG||0 (0.0)||5 (0.6)|
|45-64||UCC||112 (55.7)||769 (30.8)|
|TCC||40 (19.9)||333 (13.3)|
|AVF||44 (21.9)||1,365 (54.6)|
|AVG||5 (2.5)||31 (1.3)|
|65-74||UCC||234 (51.3)||735 (32.5)|
|TCC||93 (20.4)||337 (14.9)|
|AVF||126 (27.6)||1,157 (51.2)|
|AVG||3 (0.7)||32 (1.4)|
|>74||UCC||380 (47.9)||886 (31.3)|
|TCC||168 (2.12)||478 (16.9)|
|AVF||239 (30.1)||1,434 (50.6)|
|AVG||6 (0.8)||34 (1.2)|
The crude all-cause mortality curve associated with any type of CVC as the first VA used was always above that for AVF at any time during the first year of follow-up (
Crude all-cause mortality rates by month and initial vascular access type.
The all-cause mortality risk of patients switching from a CVC to an AVF during the first year (n = 1932) decreases by half (OR: 0.46, 95% CI: 0.36-0.58) compared with patients dialyzed for as long through a CVC (using a single CVC or changing from one CVC to another) (n = 873). The all-cause mortality risk of patients switching from an AVF to a CVC during the first year (n = 226) is 6-fold (OR: 5.88, 95% CI: 4.00-9.09) compared with patients dialyzed for as long through an AVF (using a single AVF or changing from one AVF to another) (n = 2945).
Characteristics of the patients who died within 120 days (early period) and from 121 to 365 days (late period) after initiating HD
Of the 1481 patients who died during the first year of follow-up, 577 (39%) died within 120 days (early period) and 904 (61%) from 121 to 365 days (late period) after initiating HD. No significant differences between either group of patients in age or in the distribution of virtually all comorbidities were found (
Characteristics of the patients who died within 120 days and from 121 to 365 days after initiating hemodialysis
|Death ≤120 days (n = 577)||Death 121-365 days (n = 904)||p-value1|
|2UCC = untunneled central vein catheter; TCC = tunneled central vein catheter; AVF = arteriovenous fistula; AVG = arteriovenous graft.|
|Age group (years)||18-44||16||2.8||15||1.7||0.378|
|Primary renal disease (PRD)||Glomerular||51||8.8||67||7.4||0.022|
|Duration of pre-dialysis nephrology care (years)||<1||236||42.4||291||32.9||<0.001|
|Initial comorbidity||Coronary artery disease||180||31.4||294||32.8||0.571|
|Cardiac conduction disorders||192||33.6||261||29.1||0.073|
|Peripheral vascular disease||191||33.3||309||34.6||0.601|
|Chronic respiratory disease||163||28.4||250||27.8||0.816|
|Diabetes (not PRD)||87||15.2||96||10.7||0.011|
|End-stage renal disease presentation||Unknown chronic renal disease||105||18.4||125||14.0||<0.001|
|Acute-on-chronic renal disease||232||40.7||311||34.8|
|Period of hemodialysis inception||2000-2005||330||57.2||509||56.3||0.737|
|First vascular access2||UCC||338||58.6||408||45.1||<0.001|
The crude all-cause mortality rate (deaths/100 patient-years) was significantly higher during the early period (18.3, 95% CI: 16.8-19.8) compared to the late period (15.4, 95% CI: 14.5-16.5). This rate peaked at 90 days, reaching a crude mortality rate of 21.6 deaths/100 patient-years and, then, dropped until remaining stable around a rate of 15 deaths/100 patient-years from 121 to 365 days after HD inception (
Cause-specific mortality rates were significantly higher in the early than in the late period for virtually all-causes (
Cause-specific mortality rates and 95 confidence intervals for the ≤120 days and 121 to 365 days periods.
VA profile of incident patients who died within (the first) 120 days (early period) and from 121 to 365 days (late period) after initiating HD
The distribution of the first VA type was significantly different between the early and late mortality periods (
The crude all-cause mortality rate (deaths/100 patient-years) for UCC was significantly higher during the early mortality period (31.2, 95% CI: 28.0-34.6) compared to the late period (21.3, 95% CI: 19.3-23.6). The highest crude all-cause mortality rate (deaths/100 patient-years) associated with the CVC was recorded during this period: 37.4 at 60 days for UCC and 29.9 at 90 days for TCC.
Regarding starting HD with a mature AVF (reference), the adjusted multivariate OR of all-cause mortality risk for the patients using UCC or TCC was 3.66 (95% CI: 2.80-4.81) and 2.97 (95% CI: 2.17-4.06) during the early period, and 1.87 (95% CI: 1.56-2.25) and 1.98 (95% CI: 1.66-2.44) during the late period. Regarding cardiovascular mortality, 2.76 (95% CI: 1.90-4.01) and 1.84 (95% CI: 1.17-2.89) during the early period, and 1.79 (95% CI: 1.36-2.37) and 1.98 (95% CI: 1.45-2.71) during the late period. Regarding infection-related mortality, 6.62 (95% CI: 3.11-14.05) and 4.58 (95% CI: 2.00-10.52) during the early period, and 1.80 (95% CI: 1.17-2.75) and 1.54 (95% CI: 0.93-2.55) during the late period.
Those patients who initiated HD by any type of CVC in Catalonia had a higher associated all-cause mortality risk over time compared to those patients with a mature AVF at HD inception, as has been previously reported (5-6-7-8-9-10-11-12-13). Gruss et al showed a risk-adjusted all-cause mortality rate 1.86 times higher for patients who started HD with a TCC than for those patients using an AVF, and demonstrated that patients who needed a TCC at some point during follow-up had a risk-adjusted mortality rate 1.68 times higher than those patients who had always used an AVF (10). From the Scottish Renal Registry (2009-2011), Bray et al reported that patients using only TCC during follow-up had higher adjusted risk of all-cause, cardiovascular- and infection-related cause of death compared with patients dialyzing only with an arteriovenous access (21).
Using a TCC at the time of HD initiation in Catalonia is independently associated with the highest adjusted risk of death over time related to AVF, even above the UCC. Why don’t TCC and UCC share the same associated all-cause mortality risk? The answer may be related to the duration of CVC exposure, significantly higher for TCC than for UCC. Regarding this “time factor”, Gruss et al reported that the mortality risk is graded according to the length of TCC exposure: the risk-adjusted all-cause mortality rate was 7.66 times higher for patients who were dialyzed with a TCC for over 52% of the follow-up time in relation to patients with a TCC for less than 18% of the follow-up time (10).
Confirming other studies (15, 16), the use of a CVC at first HD session is one factor independently associated with the increased risk of adjusted all-cause mortality during the first year of HD treatment in Catalonia. Therefore, the VA type at HD initiation should be included in predictive models of patient’ survival such as those developed and validated by Mauri et al using data from RMRC (22, 23).
The crude all-cause mortality rate was the highest during the early period of follow-up (first 120 days) and peaked in month 3 after HD inception in Catalonia. According to the United States Renal Data System (USRDS), all-cause mortality rate peaked in month 2 following HD initiation (24). This temporal profile is very similar with the crude all-cause mortality rate associated with any type of CVC in Catalonia because it peaked in month 2 and 3 after starting HD through UCC and TCC, respectively. Lukowsky et al showed that the highest all-cause mortality rate among 18,707 incident HD patients occurred during the first 6 months, including an 80% higher death risk within the first 2 months, and using CVC as the first VA explained 34% of all deaths after HD inception (25).
Why this excess of mortality risk associated with the CVC as the initial VA? Catheter-related bacteremia can explain some cases of death in incident patients using a CVC (infection-related mortality) (26, 27). In fact, in Catalonia both UCC and TCC were associated with a significantly higher risk of infection-related death during the first 120 days after HD inception - that is within the highest mortality risk period.
However, sepsis secondary to CVC cannot fully explain the increase in the mortality rate related to CVC. Confirming previous findings (11), we have demonstrated a significantly higher cardiovascular mortality risk associated with starting HD treatment by CVC during the first year of follow-up. This risk remains significantly higher when considering UCC and TCC separately or also both early and late periods of mortality. The reason for this increased one-year cardiovascular mortality risk is unclear. It has been postulated that the use of CVC itself, through the foreign body effect and/or the presence of bacterial biofilm without overt CVC infection, may amplify the baseline inflammatory status which, in turn, has been linked with an increased cardiovascular risk (28-29-30-31-32-33). It appears that the elapsing time from CVC insertion until developing a fatal cardiovascular disease is limited and would be against this hypothesis. However, according to the CHOICE study, CVC insertion is associated with a heightened state of inflammation that persists even after 60 days from placement (34).
In a recent adjusted multivariate logistic analysis, both age and comorbidity are risk factors independently associated with the likelihood to use a mature AVF as the first VA in the incident patient (35). It has been suggested that some patient characteristics, such as older age and the presence of cardiovascular comorbidities, are associated, on the one hand, with a lower probability to start chronic HD through a mature AVF (and an higher likelihood to use a CVC) and, on the other hand, with a higher cardiovascular mortality risk during the first year of HD treatment (36). In this regard, the clinical profile between patients who died and who survived during the first year of follow-up in the present study was significantly different suggesting the existence of selection bias (1, 4). In addition to age and comorbidity, other unmeasured confounding factors could play a role in the mortality rate often attributed to CVC (37). In this regard, Sachdeva et al have pointed out that CKD patients initiating HD with TCC or AVG had a higher inflammatory status
This study has a number of weaknesses inherent to any study performed completely using patients’ data from a population register database, in which the variables utilized are restricted in number and can have low clinical specificity. The adjusted competitive all-cause mortality risk over time related to VA was calculated according to the VA used only in the first HD, without accounting for further changes in VA type during the follow-up. Another limitation of this study is the small proportion of incident patients that initiated HD through AVG and, therefore, conclusions about the mortality associated with this type of VA are not possible in Catalonia.
Strengths of the present study include its large sample size (almost 10,000 incident HD patients) and the prolonged duration of the study period (12 years), sufficient numbers and sufficient time to make valuable conclusions about the mortality risk associated with VA in Catalonia. Another strength of our study is that, in contrast with previous epidemiological studies where UCCs and TCCs were combined into one “CVC group” (15, 16), we have considered UCC and TCC separately to analyze possible differences between both types of CVC. In the present study, we included the mortality data from day 1 of HD treatment unlike other studies that only consider patients who died after day 90 of HD inception. That is, they excluded all incident HD patients dying within the first 3 months after HD initiation (11). According to USRDS, death rates from day 1 are 17-20% higher than those followed from day 90 (24).
In conclusion, the present registry-based study over a period of 12 years shows that around 50% of ESRD patients started HD without a mature AVF in Catalonia. Initiating HD treatment by any type of CVC was independently associated with a higher all-cause mortality risk over time than with a mature AVF. The period of the highest crude all-cause mortality rate in Catalonia was the first 120 days after HD inception. During this period, the adjusted OR of death for all-cause, cardiovascular- and infection-related mortality was significantly higher for the incident patients who started HD through any type of CVC regarding initiating HD with a mature AVF. Therefore, about half incident HD patients in Catalonia are exposed annually to an excessive mortality risk related to CVC, which is a potentially modifiable risk factor by means of early AVF placement.
To all the staff at Centers and Services providing attention to end-stage renal disease patients in Catalonia. To the vascular accesses working group members of the Catalan Society of Nephrology (SCN) in alphabetical order: J. Feixas (Hospital General de Vic), N. Fontseré (Hospital Clínic i Provincial), F. Graterol (Hospital Germans Trías i Pujol), J. Ibeas (Consorci Hospitalari Parc Taulí), J. Martínez (Fundació Puigvert), M. Ramírez de Arellano (Hospital de Terrassa), R. Sans (Hospital de Figueres). The promoter of this work was the Organització Catalana de Trasplantaments (OCATT) and it could never have been carried out without their support.
- Roca-Tey, Ramon [PubMed] [Google Scholar] 1, 2, * Corresponding Author (firstname.lastname@example.org)
- Arcos, Emma [PubMed] [Google Scholar] 3
- Comas, Jordi [PubMed] [Google Scholar] 3
- Cao, Higini [PubMed] [Google Scholar] 3, 4
- Tort, Jaume [PubMed] [Google Scholar] 3
- Catalan Renal Registry Committee, and the [PubMed] [Google Scholar] 3
Coordinator of the Vascular Accesses Working Group of the Catalan Society of Nephrology (SCN), Barcelona - Spain
Department of Nephrology, Hospital de Mollet, Barcelona - Spain
Registre de Malalts Renals de Catalunya (RMRC), Organització Catalana de Trasplantaments (OCATT), Health Department of Catalonia, Barcelona - Spain
Department of Nephrology, Hospital del Mar, Barcelona - Spain