Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis

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Journal of the Formosan Medical Association (2018) xx, 1e8

Available online at www.sciencedirect.com

ScienceDirect journal homepage: www.jfma-online.com

Original Article

Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis Chien-Hua Chiu a, Chun-Yeh Wang a, Sin-Hua Moi b, Chien-Hsing Wu a, Cheng-Hong Yang b, Jin-Bor Chen a,* a Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan b Department of Electronic Engineering, National Kaohsiung University of Applied Sciences, Kaohsiung, Taiwan

Received 7 June 2018; received in revised form 15 August 2018; accepted 29 August 2018

KEYWORDS Tunneled catheter; Arteriovenous fistula; Mortality; Hemodialysis

Purpose: We examined the association between catheter use for maintenance hemodialysis (HD) and mortality/hospitalization in a cohort of patients with prevalent HD. Methods: In this study, 70 HD patients with tunneled cuffed central venous catheters (TCVCs) from a Taiwanese HD center during 2014e2016 were enrolled and compared with 70 matched HD patients with native arteriovenous fistulae (AVF). The compared variables included demographic parameters and laboratory and dialysis-related indices. Cox regression analysis was used to assess the risk of mortality/hospitalization within a year. Results: Low baseline serum albumin levels were found in patients with TCVCs (3.64 g/dL vs 3.79 g/dL, p Z 0.030). The mortality rates of patients with AVF and TCVCs were 14 per 1000 patients and 171 per 1000 patients, respectively. Infection was the leading cause of mortality/hospitalization in patients with TCVCs. Using multivariate analyses, the risk of death was found to be significantly higher in patients with TCVCs than in those with AVF (Hazard ratio [HR] 12.15, 95% CI 1.16e127.17; p Z 0.037). Patients with TCVC also had a higher hospitalization rate (HR 1.33, 95% CI 0.71e2.49; p Z 0.369) (not statistically significant). Conclusion: Catheter use for maintenance HD was associated with increased all-cause mortality. Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/bync-nd/4.0/).

* Corresponding author. N123, DaPei Rd, Niao Song Dist, Kaohsiung City 80833, Taiwan. Fax: þ886 7 7322402. E-mail address: [email protected] (J.-B. Chen). https://doi.org/10.1016/j.jfma.2018.08.025 0929-6646/Copyright ª 2018, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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Introduction Vascular access is required for hemodialysis (HD) procedures. There are several types of vascular access in clinical practice, such as tunneled/non-tunneled central venous catheters, cuffed/non-cuffed central venous catheters, native arteriovenous fistulae (AVF), and arteriovenous grafts (AVG). The choice of vascular access is determined by several clinical factors, which include the patient’s vascular status, comorbidity, nutritional status, functional performance, physician’s preference, timing of nephrologist’s referral, the pre-dialysis insurance status, etc. Generally, catheter use in HD increases the risk of thrombosis,1,2 infection,3e8 low delivered HD dose,9 and reduced survival.2,10 Moreover, catheter use is associated with higher mortality when compared to the use of native AVF.11e15 Accordingly, clinical guidelines strongly recommend AVF for long-term HD.16,17 A limiting factor in examining the association between the type of vascular access and mortality in HD patients is the constant change, over time, in the type of vascular access used. In a previous Medicare procedure codes study, Xue et al.,14 found that incident HD patients who used catheters had a 70% higher risk of mortality in the first year than did those who used AVF. The study did not determine duration of the catheter use, and therefore could not adjust the potential time-effect of catheter use on the risk of subsequent mortality in HD patients. The CHOICE study.18 addressed the issue of mortality by accounting for the changes in vascular access types over time. The study demonstrated that the percentage of catheter use in HD initiation decreased from 66% to 34% after six months. In contrast, AVF use increased from 14% in HD initiation to 26% after six months. Investigators found that the vascular access type change was more likely to occur in the first six months after HD initiation. Accordingly, the study suggested that prevalent HD patients receiving HD for more than six months may provide more reliable data for examining the association between vascular access types and subsequent mortality. The current study aims to address this issue. A cohort of prevalent HD patients who undergo constant vascular access type changes for their maintenance HD therapy were recruited. We examined incidences of allcause mortality/hospitalizations between native AVF and TCVCs over a 12-month period.

Methods Subjects Medical records of HD patients who received regular dialysis treatments between 2014 and 2016 at Kaohsiung Chang Gung Memorial Hospital in Taiwan were reviewed. Eligibility criteria for this study included ages >18 y, survival three months after HD initiation, HD thrice weekly and no change of HD vascular access type occurred during the study period. Patients who underwent TCVC HD during 2014e2016 were considered the test subjects. The AVF patients, designated as controls, were obtained by searching the HD database for matching factors that included age (5 years), sex, and dialysis vintage (1 years). Total 1088 AVF patients

C.-H. Chiu et al. were eligible for being matched in initial. After matching with TCVCs patients using current study eligible criteria, 70 of 1088 patients was defined as AVF matched group, and remaining 1018 AVF patients is defined as the AVF not matched groups. The distribution of baseline characteristics including age, gender, dialysis vintage, DM, primary disease, and albumin of AVF not matched, AVF matched, TCVC matched groups were summarized in Supplementary Table 1. In this study, 70 TCVC subjects were matched to 70 AVF controls for a total of 140 enrolled subjects. The site of TCVC insertion was the right internal jugular vein. Native AVF were created predominately in the non-dominant left forearm. Each patient was monitored for hospitalizations and all-cause mortality within 12 months. In this study, we defined catheter-related blood stream infections as occurring when the same organism was cultured from the peripheral blood and two catheter hubs. TCVC components were made of silicone (Medtronic, USA).

Demographic and clinical data Data on age, sex, primary kidney disease, diabetes, medication use (including vitamin D, antihypertensives, iron, and erythropoiesis-stimulating agents), causes of mortality/hospitalization, type of vascular access (native AVF or TCVC), and cardiothoracic (CT) ratio by chest radiographic examination, were collected during the study period. Physical performance status was evaluated by Karnofsky Performance Status Score (KPS). Blood sampling was performed on the Wednesday/Thursday before the commencement of HD. Baseline data included hemoglobin (Hb), albumin, blood urea nitrogen (BUN), creatinine (Cr), potassium (K), serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), ferritin, Kt/V urea (Daugirdas method), and urea reduction ratio (URR). URR was calculated using the following formula: [pre-dialysis BUN e post-dialysis BUN/pre-dialysis BUN]  100%. Kt/V urea score Z -Ln (R e 0.008  t) þ [4 e (3.5  R)]  UF/W, where R represents the ratio of post-dialysis BUN to pre-dialysis BUN, t represents the duration of dialysis in hours, UF represents the ultrafiltration amount in liters, and W is the post-dialysis body weight in kg. All blood samples were analyzed using commercial kits or an autoanalyzer (Hitachi 7600-210, Hitachi Ltd., Tokyo, Japan). Albumin was measured using the Bromocresol green method. ALP was measured using a colorimetric assay, according to manufacturers’ instructions, via the hydrolysis of p-nitrophenyl phosphate (Roche Diagnostic Indianapolis, USA), and iPTH was determined using a chemiluminescent immunoassay (Siemens Healthcare Diagnostics Inc., USA). To determine the CT ratio for each patient, chest radiography following HD was performed. Cardiac size was measured as the distance between parallel lines drawn from the most lateral points on both sides of the heart. Thoracic width was measured as the distance between parallel lines drawn down the inner aspect of the widest points of the rib cage. The CT ratio was defined as cardiac size/thoracic width. HD data collection also included various components of HD dialyzers (cellulose triacetate, polymethylmethacrylate, polysulfone, polyethersulfone), surface area of HD dialyzers, HD frequency, HD duration in each session, and blood flow

Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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Tunneled venous catheter in hemodialysis rates of vascular access types. The dialysate flow rate was 500 cc/min for all subjects. Each subject was observed since the first date they were underwent AVF or TCVC HD treatment during 2014e2016. For those who have received AVF or TCVC HD treatment before 2014 year, we had given an initial index date since 1st Jan 2014. The hospitalization is defined as the 1st hospitalization after observation. The follow-up interval of hospitalization is counted from the first observation date or initial index date until the date of first time hospitalization or end of study observation (within 12 months from first observation date). The all-cause mortality is defined as the patients who expired during study follow-up interval. The all-cause mortality interval is counted from the first observation date or initial index date until the expired date or end of study observation (within 12 months from first observation date). This study was approved by the Committee on Human Research at Kaohsiung Chang Gung Memorial Hospital (101e1595B) and conducted in accordance with the Helsinki Declaration. Informed consent was not required from the study subjects, according to retrospective data review regulations of the Committee on Human Research at Kaohsiung Chang Gung Memorial Hospital.

Statistical analysis The distribution of TCVCs and AVF controls were summarized using mean (standard deviation), median (interquartile range), or frequency (percentage). The difference between both groups was estimated using the correct application of either the chi-squared test or the independent two-sample t-test. The Cox regression analysis was performed to evaluate the risk factors for all-cause mortality and hospitalization within 12 months. The multivariate Cox regression model analysis only included the variables with p-values < 0.2 in univariate analysis. The cumulative risk of all-cause mortality and hospitalizations were visualized using a KaplaneMeier curve and the comparison risk of all-cause mortality and hospitalizations between TCVC and controls was estimated using a log-rank test. In all analyses, p-values < 0.05 were considered statistically significant. All statistical analyses were conducted using STATA (version 11.1).

Results A total of 70 patients with native AVF and 70 patients with TCVCs were analyzed in this study. The causes of TCVC use included unsuitable vessels for AVF creation after previous episodes of fistula failure (n Z 31), as well as surgeon’s and patient’s preferences (n Z 39) such as poor candidates for arteriovenous access creation, critically ill condition at the timing for access creation and personal preference in patients. Table 1 shows the baseline characteristics of these patients. There were no statistically significant differences between patients with AVF or TCVC access types in relation to age, sex, dialysis vintage, diabetes, categories of etiology for kidney failure and dialyzers, dialysis duration and blood flow rate in each HD session, or medication use including vitamin D, antihypertensive, iron, erythropoietin-

3 stimulating agents and performance status. Comparing cohorts of AVF not matched, AVF matched, TCVC matched, subjects in AVF not matched showed significantly younger than those in other two cohorts (61.87, vs. 66.27 vs. 66.43 years old, respectively). Dialysis vintage also showed significantly longer in AVF not matched cohort comparing with other two cohorts (7.05 vs.2.29, 2.25 years, respectively). Meanwhile, serum albumin exhibited significantly higher levels in AVF not matched cohort comparing with other two cohorts (3.89, vs.3.79 vs. 3.64 g/dL, respectively) (supplementary table 1). Patients with TCVCs receiving the HD dialyzer >2.0 m2 had low percentages. Patients with AVF had significantly higher serum albumin than those with TCVCs. Within a year, only one of the 70 patients with AVF died, while 12 out of the 70 patients with TCVCs died. The mortality rates were 93, 14, and 171 per 1000 dialysis patients for the total, control, and catheter subjects, respectively. Fatal infection was the leading cause of mortality. Detailed information on the causes of mortality is shown in Supplementary Table 2. Among the deaths, none were related to AVF or catheter use infections. Pneumonia caused infections in 1 patient with AVF and 3 patients with TCVCs. Two cases with unknown sources of sepsis also occurred in patients with TCVCs. The bacteria in patients with TCVCs included Klebsiella pneumoniae (2), Pseudomonas aeruginosa (2), and a yeast-like organism (1). Hospitalizations were higher in patients with TCVCs than in those with AVF (n Z 28, 40% vs. n Z 21, 30%, p Z 0.215) (Table 1). Dialysisrelated complications were the leading causes of hospitalizations in patients with AVF (fluid overload, hyperkalemia, and metabolic encephalopathy). In contrast, infectious diseases were the main causes of hospitalizations in patients with TCVCs (Supplementary Table 3). The causes of infection in patients with TCVCs included: pneumonia (3), urinary tract infections (3), intra-abdominal abscess (1), infectious spondylitis (1), cellulitis in the leg (1), and unknown sources of sepsis (2). The bacteria in patients with TCVCs included: Staphylococcus aureus (1), K. pneumoniae (2), P. aeruginosa (2), a yeast-like organism (1), and those that could not be cultured (5). Figs. 1 and 2 show the KaplaneMeier curves for all-cause mortality/hospitalizations in patients with AVF and TCVCs. Table 2 shows the results of the univariate and multivariate analyses for all-cause mortality within the 12-month study. The risk of death was higher in patients with TCVC than in those with AVF (HR e 12.15, 95% CI - 1.16e127.17; p Z 0.037). Table 3 shows the results of the univariate and multivariate analyses for hospitalizations within the 12-month study. Although patients with TCVCs had higher hospitalizations than those with AVF (HR e 1.33, 95% CI 0.71e2.49; p Z 0.369), it did not reach statistical significance.

Discussion The current study examined the impact of TCVCs for maintenance HD on all-cause mortality/hospitalizations in prevalent HD patients. Their control counterparts were patients with native AVF for maintenance HD. The main difference between the current and previous studies is that

Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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C.-H. Chiu et al. Table 1

Baseline characteristics and clinical features. (n Z 140). AVF (n Z 70)

TCVC (n Z 70)

P-value

Match criteria Age (mean, SD) Male (n, %) Dialysis vintage (years) (mean, SD) Dialysis vintage (years) (median, range)

66.27 25 2.29 0.91

14.19 35.71 4.04 0.07e16.88

66.43 25 2.25 0.78

14.29 35.71 3.96 0.07e16.89

0.948 1.000 0.956

Categorical variables

n

%

n

%

DM (Yes) Primary disease A: Renal Parenchymal Diseases B: Systemic Diseases G: Unknown causes Dialyzer Cellulose Synthetic Dialyzer square meter  2.0 > 2.0 Vit D use Antihypertensive use Iron use Hospitalization Cause of mortality CV Infection Others Karnofsky Performance Status 40 50 60 70 80 90 100 URR  0.65 Cardiothoracic ratio  0.5

33

47.14

32

45.71

21 45 4

30 64.29 5.71

21 45 4

30 64.29 5.71

24 46

34.29 65.71

15 55

21.43 78.57

14 56 3 16 6 21 1 0 1 0

20 80 4.29 22.86 8.57 30 1.43 0 0 1.43

27 43 3 27 8 28 12 3 5 4

38.57 61.43 4.29 38.57 11.43 40 17.14 5.71 4.29 7.14

0 11 15 12 6 21 5 63 31

0.00 15.71 21.43 17.14 8.57 30.00 7.14 90 44.29

3 22 10 12 5 11 7 65 29

4.29 31.43 14.29 17.14 7.14 15.71 10.00 92.86 41.43

Continuous variables

mean

SD

mean

SD

Dialysis duration: min Blood analysis Hb (g/dL) Albumin (g/dL) Cr (mg/dL) Ca (mg/dL) P (mg/dL) K (meq/L) Kt/V

231

17.21

227.14

18.11

0.199

10.38 3.79 9.29 9.17 4.65 4.36 1.66

1.31 0.4 2.59 0.78 1.41 0.7 0.33

9.91 3.64 8.42 9.16 5.06 4.5 1.6

1.33 0.42 2.71 0.83 1.29 0.86 0.33

0.037 0.030 0.055 0.986 0.074 0.308 0.309

median

interquartile range

median

interquartile range

250 24000

(230e260) (16000e24000)

250 24000

(220e260) (16000e24000)

0.324 0.875

61 82 200 451

(53e77) (64e108) (87e439.9) (288e581.4)

67.5 84.5 158.5 443.6

(56e81) (64e120) (101e370.8) (259.8e704.7)

0.151 0.147 0.338 0.832

Blood flow rate (cc/min) EPO mean dose/Month Blood analysis BUN (mg/dL) Alkaline phosphatase (IU/L) iPTH (pg/mL) Ferritin (ng/mL)

0.865 1.000

0.090

0.016

1.000 0.044 0.573 0.215 0.002

0.083

0.735 0.779

P-value for categorical variables were estimated by chi-squared test and continuous variables were estimated by independent twosample t-test. Abbreviations: CNS, central nervous system; CV, cardiovascular; EPO, erythropoietin; iPTH, intact parathyroid hormone; URR, urea reduction ratio. Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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Tunneled venous catheter in hemodialysis

Figure 1

KaplaneMeier curve for all-cause mortality.

in this study, subjects received a permanent vascular access type throughout the study period.3,4,8,14 Therefore, the time-effect of vascular access types on mortality can potentially be diminished. We found that patients with TCVCs demonstrated significantly higher risk for all-cause mortality compared to those with native AVF. These findings agree with previous studies on HD patients with catheter use. In the U.S. Renal Data System (USRDS) Dialysis Morbidity and Mortality Study (Wave 1), prevalent HD patients with TCVCs had an increased mortality risk when compared with those with AVF.12 The results were proven in subsequent large cohort studies including the U.S. ESRD Network 6.13 the U.S. Medicare dialysis population.14 the Australia and New Zealand Dialysis and Transplant Association Registry for incident HD patients,15 the CHOICE study,18 and the European study.19 It is clear that TCVC use, either in incident or prevalent HD patients, increased the risk of mortality when compared to that in patients with AVF. In our previous study, incident HD patients who were converted from TCVC use to AVF or AVG exhibited lower mortality rates within 1e3 years after initiation of HD.20 The current study also shows that catheter use for maintenance HD increased the risk of mortality in the Taiwanese prevalent HD population. A similar trend of catheter use and morbidity has been observed in the current and aforementioned previous studies.

Figure 2

KaplaneMeier curve for hospitalization.

5 In the present study, we found age (p Z 0.051) was a risk factor for death in our patients. A similar result has been reported in previous studies including National Report from Taiwan Society of Nephrology.13,14,21 We also examined the influence of physical performance upon death risk in our study. KPS was utilized to evaluate physical performance status in our patients. We did not find KPS associated with risk for mortality and hospitalization by Cox regression analyses. This result is contrary to prior studies those demonstrated lower KPS was correlated with higher death risk.22,23 The plausible explanation included small sample size and relative short-term follow-up period in our study. Therefore, our result cannot refute the critical role of physical performance on mortality in dialysis patients. Infection is the main cause of mortality in prevalent HD patients. Our study demonstrated that infection was the leading cause of mortality/hospitalizations both in patients with TCVC and AVF. In our previous studies, we found that patients who converted from catheter use to AVF or AVG showed a decreased risk of infection compared to those with permanent catheter use.20 Similar results were also documented in previous studies.12,13,15,18,19 In addition, the current study found that most of the infections either for mortality or hospitalization were not related to the vascular access type which agrees with recent studies on HD vascular access types and mortality. The Dialysis Outcomes and Practice Patterns Study (DOPPS), from 1996 to 2011 showed that HD vascular access type complications did not mediate mortality in the different HD access types for incident HD patients.24 Similarly, in the US Renal Data System report linked with Medicare,25 patients using catheters after failed HD fistula creation demonstrated lower mortality. Collectively, these studies suggest that patient factors affect the choice of HD vascular access types. However, other mechanisms that cause infections in HD catheter use cannot be ignored. Several clinical factors involved in this predisposition include: procedure performance, vascular anatomy, competence of nephrologists, dialysis adequacy indices, nutritional status, and self-care quality, etc. In the current study, the main cause of mortality in patients with TCVCs was related to infectious diseases, although an analysis of the related bacteria suggests a low probability that the infection originated at the TCVC site. Ultimately, to properly address this issue, a more detailed study of infection control in catheter care via accurate records of clinical situations and individual audits of patient care is required. We found different causes for hospitalizations in each cohort. Patients with AVF were hospitalized mainly for dialysis-related and gastro-hepatic causes. In contrast, patients with TCVCs were hospitalized mainly for infectious diseases. Dialysis-related causes included fluid overload, hyperkalemia, and metabolic encephalopathy, etc. However, the dialysis adequacy indices (Kt/V, and URR) and CT ratio were not significantly different between the two cohorts. We speculate that these dialysis-related events are mainly due to the patient’s poor self-care. Although the majority of the hospitalizations in those patients with TCVC were related to infections, none were related to catheter use according to the definition of HD catheter-related bloodstream infection.26 However, the infection episodes occurred less than a year after the TCVC implant, which

Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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C.-H. Chiu et al. Table 2

Cox regression for all-cause mortality within 12 months follow-up.

Variables

TCVC (vs. controls) Age (years) Male Dialysis vintage (years) DM (Yes) Dialyzer (Synthetic) Dialyzer square meter > 2 Dialysis duration: min Blood flow rate Vit D use Antihypertensive use Iron use EPO mean dose/Month Karnofsky Performance Status Blood analysis Hb (g/dL) Albumin (g/dL) BUN (mg/dL) Cr (mg/dL) Ca (mg/dL) P (mg/dL) K (meq/L) Alkaline phosphatase iPTH (pg/mL) Ferritin (ng/mL) Kt/V URR  0.65 (%) Cardiothoracic ratio  0.5 (%) Hospitalization (%)

Univariate

Multivariate*

HR

95% CI

P

HR

95% CI

P

14.84 1.07 0.85 1.05 0.47 2.40 0.20 1.00 0.98 2.10 1.68 1.83 0.99998 0.96

1.93e114.27 1.01e1.13 0.28e2.59 0.94e1.16 0.14e1.53 0.53e10.84 0.07e0.62 0.97e1.04 0.97e0.998 0.27e16.16 0.55e5.16 0.41e8.28 0.9999e1.00005 0.93e0.999

0.010 0.014 0.773 0.402 0.210 0.255 0.005 0.898 0.031 0.476 0.366 0.431 0.575 0.045

12.15 1.12

1.16e127.17 0.9996e1.25

0.037 0.051

1.34

0.23e7.77

0.748

0.98

0.96e1.005

0.125

1.03

0.97e1.09

0.354

0.78 0.09 1.02 0.64 0.66 0.80 0.53 1.01 1.0004 1.0002 0.83 0.96 0.43 2.99

0.55e1.12 0.03e0.27 0.98e1.05 0.49e0.83 0.32e1.37 0.53e1.198 0.26e1.097 1.01e1.02 0.999e1.002 0.999e1.001 0.12e5.71 0.12e7.43 0.1e1.78 0.98e9.18

0.179 <0.001 0.340 0.001 0.266 0.279 0.087 <0.001 0.559 0.631 0.854 0.970 0.242 0.055

0.70 0.14

0.42e1.16 0.02e1.04

0.166 0.054

1.04

0.72e1.50

0.840

0.55 1.004

0.16e1.87 0.995e1.01

0.340 0.350

0.91

0.23e3.68

0.897

*The variables show p-value < 0.2 in univariate analysis were included.

emphasizes the importance of infection awareness in patients with TCVCs. In the current study, patients with TCVCs showed a low HD dialyzer >2.0 m2 percentage use compared to those with AVF. Furthermore, patients with TCVCs did not show low results for dialysis parameters such as adequacy indices, dialysis blood flow rates, or dialysis durations within the HD sessions. However, serum albumin levels were significantly lower in patients with TCVC implants. In summary, patients with TCVC implants, in the current study, did not show HD inadequacy. These findings were contrary to previous studies. Previous reports generally showed that catheter use for HD resulted in low blood flow rates, dialysis doses, and missed or reduced dialysis sessions.27 Based on our findings, we speculate that the attributable causes of increased risk for mortality/hospitalization in patients with TCVCs are factors other than those related to the HD procedure. In the current study, low serum albumin levels were associated with the risk of mortality/hospitalization using the univariate analysis; however, the effect approached neutral effect using the multivariate analysis. Accordingly, we realized that when catheter use was unavoidable in clinical circumstances for maintenance HD, dialysis adequacy indices were not factors precluding catheter use. Competent and qualified bedside catheter nursing care, and apparently healthy patients,

were the main components for the reduced risk of complications with catheter use. Finally, TCVCs are still a risk for all-cause mortality in HD patients following the Cox regression multivariate analysis. Among the etiologies, infections were the main cause of mortality/hospitalization in those patients with TCVCs. Therefore, careful infection surveillance and management are important for those with TCVC implants. The serum measurement of inflammatory markers may help determine whether the presence of hyperferritinemia in dialysis patients is due to iron overload or inflammation; this may be particularly helpful when the serum ferritin level is > 800 ng/mL but the serum transferrin saturation is within the normal range (<50 percent).28 The association between increased mortality and serum ferritin levels >800 ng/mL appears to be primarily due to the confounding effect of inflammation.29 In our study, mean ferritin level in both groups are less than 500 ng/mL which means no obvious inflammatory status existed. Furthermore, the HR was nearly neutral value by Cox regression analysis for hospitalization. We supposed serum ferritin levels in the present study not contributing to the infectious impact. Although the current study showed a significant association between TCVC use and all-cause mortality/

Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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Tunneled venous catheter in hemodialysis Table 3

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Cox regression for hospitalization within 12 months follow-up.

Variables

TCVC (vs. controls) Age (years) Male Dialysis vintage (years) DM (Yes) Dialyzer (Synthetic) Dialyzer square meter > 2 Dialysis duration: min Blood flow rate Vit D use Antihypertensive use Iron use EPO mean dose/Month Karnofsky Performance Status Blood analysis Hb (g/dL) Albumin (g/dL) BUN (mg/dL) Cr (mg/dL) Ca (mg/dL) P (mg/dL) K (meq/L) Alkaline phosphatase iPTH (pg/mL) Ferritin (ng/mL) Kt/V URR  0.65 (%) Cardiothoracic ratio  0.5 (%)

Univariate

Multivariate*

HR

95% CI

P

HR

95% CI

P

1.70 1.00 1.31 0.96 0.86 0.92 0.62 1.00 1.00 0.78 1.50 1.79 1.00001 0.99

0.96e2.996 0.98e1.03 0.71e2.41 0.89e1.05 0.49e1.51 0.49e1.704 0.35e1.11 0.98e1.01 0.99e1.01 0.19e3.203 0.84e2.69 0.804e3.997 0.99997e1.00005 0.98e1.01

0.067 0.711 0.381 0.363 0.592 0.783 0.108 0.871 0.570 0.728 0.172 0.154 0.532 0.235

1.33

0.71e2.49

0.369

1.04

0.52e2.08

0.915

1.39 1.85

0.73e2.67 0.77e4.48

0.318 0.170

0.82 0.32 1.01 0.86 0.95 1.06 1.03 1.01 0.9998 1.001 1.59 1.31 1.07

0.67e0.99 0.16e0.61 0.99e1.03 0.77e0.97 0.67e1.35 0.86e1.3 0.71e1.49 1.002e1.01 0.999e1.001 1.0004e1.001 0.64e3.95 0.41e4.23 0.56e2.03

0.044 0.001 0.196 0.011 0.771 0.603 0.892 0.004 0.662 <0.001 0.316 0.648 0.845

1.04 0.60 1.02 0.91

0.83e1.31 0.24e1.52 0.998e1.04 0.78e1.07

0.730 0.281 0.081 0.244

1.002

0.998e1.01

0.345

1.0006

1.0001e1.001

0.028

*The variables show p-value < 0.2 in univariate analysis were included.

hospitalization in prevalent HD patients, there were some limitations. First, retrospectively selecting patients from one large HD center could not prevent the effect of center-specific management. Secondly, early deaths could not be avoided in studies involving prevalent HD patients. Moreover, the number of deaths was relatively low in the current study. Therefore, a more detailed analysis of the causes of mortality was impossible on the basis of the low death rate. The mortality rate of 93 per 1000 dialysis patients among the total population was lower than the reported Taiwanese national registry annual mortality rate in HD prevalent patients of 120 per 1000 dialysis patients.21 Notably, mortality rates increased to 171 per 1000 dialysis patients in those with TCVCs compared to 14 per 1000 dialysis patients in those with AVF in the current study. Because of the unavailability comparable data for these two cohorts in the Taiwanese national registry, it was impossible to conclude whether the percentages, did or did not, meet the standard of HD care in Taiwan. Thirdly, the timing of nephrologist’s referrals was not recorded which could be an important factor considering that an early referral could influence the choice of vascular access in early stage HD and the subsequent mortality risk.30,31 Nevertheless, the current study examined the impact of permanent TCVCs on all-cause mortality and morbidity in prevalent HD patients during the

study period. This differs from a majority of the previous studies by examining the impact of catheter use on mortality rates in HD patients. We also demonstrated that catheter use in HD patients did not result in low dialysis adequacy indices. Due to a lack of detailed patient medical information, the possibility of case-specific causes influencing the final impact of the vascular access type complications could also not be determined. In conclusion, TCVC implants for maintenance HD are related to an increased risk of all-cause mortality compared to patients with AVF, access of TCVC was not the main cause of these TCVC complications.

Author’s contributions CH Chiu: drafting the article, CY Wang: data collection and management. MS Hua: statistical analysis. CH Wu: providing intellectual content of critical importance to the work described. CH Yang: interpretation of data and revision of article, JB Chen: conception, design, interpretation of data and drafting the article.

Conflicts of interest The authors declare no conflict of interest.

Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025

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MODEL

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Acknowledgements The authors would like to thank the HD nurses who participated in the collection of clinical data for this study.

Appendix A. Supplementary data Supplementary data related to this article can be found at https://doi.org/10.1016/j.jfma.2018.08.025.

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Please cite this article in press as: Chiu C-H, et al., Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis, Journal of the Formosan Medical Association (2018), https://doi.org/10.1016/j.jfma.2018.08.025