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Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
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Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
D
PPS
Dialysis Outcomes and Practice Patterns Study
Longer Dialysis Session Length is Associated with
Better Intermediate Outcomes and Survival among
Patients on In-Center Three Times per Week
Hemodialysis: Results from the DOPPS
Francesca Tentori, Jinyao Zhang, Yun Li, Angelo Karaboyas,
Peter Kerr, Rajiv Saran, Juergen Bommer, Friedrich Port,
Takashi Akiba, Ronald Pisoni, Bruce Robinson
Nephrology Dialysis Transplantation, 2012
Introduction
• Longer dialysis session length (treatment time,
TT) has been associated with better survival
among hemodialysis (HD) patients.
• The impact of TT on clinical markers that may
contribute to this survival advantage has not
been described.
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
DOPPS Background
• International prospective cohort study of
hemodialysis patients and HD unit practices
• Uniform international data collection
• Goal: Identify HD practice patterns associated with
improved patient outcomes (adjusted for patient mix)
• Major outcomes: mortality, hospitalization, vascular
access, quality of life
• Coordinated by Arbor Research Collaborative for
Health (Ann Arbor, MI USA)
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
A Decade of DOPPS
Years:
Countries*:
Facilities:
Census Pts:
Sample Pts:
DOPPS 1
DOPPS 2
DOPPS 3
DOPPS 4**
1996-2001
2002-2004
2005-2008
2009-2011
7
12
12
12
308
322
300
382
>50,000
>17,000
>43,000
>12,800
>50,000
>11,300
>54,000
>15,000
Cross-sectional, longitudinal, representative
Comorbidities, medications, labs, QoL
Focus:
crosssections
annually
Additions:
Outcomes:
+ incident
& depression
+ process of
care &
nutrition
+3x/yr crosssections,
special study
“modules”
Quality of Life, Events, Hospitalizations, Mortality
* Japan, US, Europe (France, Germany, Italy, Spain, UK) + Australia, Belgium,
Canada, New Zealand, Sweden
** Includes oversampling of small, rural, independent facilities in US
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Methods (1)
• Sample: N=37,414 patients from DOPPS phases 1-3
on in-center 3x/week HD
• Variables of Interest: prescribed TT (120-420 min)
• Outcomes:
– Mortality: all-cause, cardiovascular, and sudden death
– Hospitalization: all-cause, cardiovascular, and CHF or
fluid overload
– Intermediate outcomes measured at study enrollment:
intradialytic weight loss, pre- and post- dialysis systolic
blood pressure (SBP), hemoglobin, white blood cell
count (WBC), serum phosphorus, potassium, albumin,
and ferritin
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Methods (2)
• Standard Regression Analysis:
– Intermediate outcomes: linear mixed models for continuous
outcomes and the Generalized Estimating Equation (GEE) method
with logit link function for dichotomized outcomes
– Mortality and hospitalization: Cox proportional hazards models
• Instrumental Variable (IV) Analysis:
(To partially account for patient-level unmeasured confounders)
– Intermediate outcomes: standard two-stage least square (TSLS) IV
method for continuous outcomes and an extended, two-stage IV
method with a linear model as the first stage and logistic
regression as the second stage for dichotomized outcomes.
– Mortality and hospitalization: extended IV approach that uses a
linear model first stage and a Cox model second stage.
• Adjustments: Age, sex, race, time on dialysis, BMI, 13 summary
comorbid conditions, residual kidney function, prescribed
blood flow rate, catheter use, DOPPS phase and country, and
accounted for facility clustering effects
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Figure 1
Facility TT by DOPPS country and phase
Facility Mean TT (min)
310
Facility
Percentile
95th
290
75th
50th
25th
270
5th
250
230
210
190
170
2 3
2 3
ANZ* BE*
2 3
1 2 3
1 2 3
1 2 3
1 2 3
1 2 3
2 3
1 2 3
1 2 3
CA
FR
GE*
IT
JP
SP*
SW*
UK
US*
* p<0.05 for increase over time
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Figure 2
Patient-level TT by DOPPS country
% of patients
100%
TT (min)
270-300 min
80%
240 min
60%
40%
210 min
20%
180 min
0%
CA
US ANZ BE
N. America
FR
GE
IT
SP
Europe/ANZ
SW
UK
JP
Japan
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Table 1
Patient characteristics by TT and region (1)
Patient TT
180 min
Number of patients All regions
Demographics
Age (years)
Sex (male)
Vintage (years)
Dry weight (kg)
210 min
240 min
270-300 min
8411 (22%)
7282 (19%) 16795 (45%) 4926 (13%)
North America (%)
4924 (32%)
4587 (29%)
5124 (33%)
948 (6%)
Eur/ANZ (%)
Japan (%)
2556 (17%)
931 (14%)
2306 (15%)
389 (6%)
7389 (49%)
4282 (65%)
2950 (19%)
1028 (16%)
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
64.5
64.3
66.3
45%
53%
58%
1.9
2.2
1.8
67.6
65.4
50.7
62.7
65.3
64.2
52%
52%
56%
2.3
3.8
4.1
72.1
64.6
51.3
58.7
62.7
60.5
63%
59%
61%
2.4
3.7
7.0
79.8
68.7
52.8
54.2
59.1
56.5
80%
70%
69%
3.7
5.1
10.7
97.3
77.4
55.6
P-value*
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
*Test of trend adjusted for country and phase, and accounted for facility clustering
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Table 1
Patient characteristics by TT and region (2)
Patient TT
180 min
Comorbidities
Diabetes
Hypertension
Coronary artery
disease
Congestive heart
failure
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
North America
Eur/ANZ
Japan
47%
28%
41%
85%
79%
75%
54%
39%
27%
45%
27%
26%
210 min
52%
26%
43%
87%
78%
71%
57%
38%
31%
48%
27%
23%
240 min
53%
29%
31%
86%
78%
67%
54%
42%
29%
46%
33%
17%
270-300 min
58%
34%
21%
89%
82%
56%
58%
51%
25%
47%
36%
13%
P-value*
<.0001
<.0001
0.13
0.08
<.0001
0.04
0.79
0.92
0.83
0.31
<.0001
0.36
*Test of trend adjusted for country and phase, and accounted for facility clustering
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Table 1
Patient characteristics by TT and region (3)
Patient TT
180 min
Labs
Hemoglobin (g/dL) North America
Eur/ANZ
Japan
Albumin (g/dL)
North America
Eur/ANZ
Japan
Catheter use
North America
Eur/ANZ
Japan
Dialysis Treatment
Blood flow
North America
(mL/min)
Eur/ANZ
Japan
High flux
North America
dialyzer use^
Eur/ANZ
Japan
210 min
240 min
270-300 min
10.7
10.5
9.4
3.6
3.6
3.6
42%
31%
9%
10.9
11.2
10.0
3.6
3.7
3.7
39%
20%
2%
11.0
11.2
9.9
3.6
3.7
3.8
42%
23%
1%
11.6
11.5
10.3
3.8
3.8
3.9
29%
14%
0%
P-value*
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
<.0001
363.4
273.1
173.2
55%
33%
62%
383.9
307.4
192.3
55%
39%
74%
384.1
301.9
193.9
50%
39%
73%
414.0
308.6
203.5
66%
51%
76%
<.0001
<.0001
<.0001
0.01
<.0001
<.0001
*Test of trend adjusted for country and phase, and accounted for facility clustering
^High flux percent calculated after excluding those with missing flux information (22%)
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Table 2
TT and mortality/hospitalization
Categorical TT [standard regression model, Hazard Ratio (95% CI) shown]
180 min
All-Cause Mortality
Unadjusted*
1.30 (1.22,1.40)
Adjusted
1.16 (1.07,1.24)
Cardiovascular Death
Unadjusted*
1.29 (1.17,1.42)
Adjusted
1.18 (1.06,1.31)
Sudden Death
Unadjusted*
1.30 (1.13,1.49)
Adjusted
1.19 (1.02,1.38)
Any hospitalization
Unadjusted*
1.14 (1.08,1.20)
Adjusted
1.10 (1.04,1.16)
Cardiovascular hospitalization
Unadjusted*
1.08 (1.01,1.16)
Adjusted
1.07 (1.00,1.15)
Hospitalization due to CHF or fluid overload
Unadjusted*
1.26 (1.11,1.43)
Adjusted
1.24 (1.09,1.42)
210 min
240 min
270-300 min
1.18 (1.11,1.26)
1.06 (0.99,1.13)
1.00 (Ref.)
1.00 (Ref.)
0.78 (0.71,0.85)
0.90 (0.83,0.98)
1.18 (1.07,1.29)
1.06 (0.96,1.17)
1.00 (Ref.)
1.00 (Ref.)
0.87 (0.77,0.98)
0.97 (0.86,1.10)
1.10 (0.96,1.26)
0.99 (0.86,1.14)
1.00 (Ref.)
1.00 (Ref.)
0.76 (0.63,0.91)
0.84 (0.70,1.01)
1.01 (0.96,1.06)
1.00 (0.94,1.05)
1.00 (Ref.)
1.00 (Ref.)
0.93 (0.89,0.98)
0.99 (0.94,1.05)
1.05 (0.98,1.13)
1.04 (0.97,1.11)
1.00 (Ref.)
1.00 (Ref.)
0.99 (0.92,1.07)
1.01 (0.93,1.10)
1.12 (0.99,1.27)
1.10 (0.97,1.24)
1.00 (Ref.)
1.00 (Ref.)
0.92 (0.79,1.08)
0.94 (0.80,1.11)
*Model stratified by DOPPS phase and country, and accounted for facility clustering
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Figure 3
TT and mortality/hospitalization
Standard regression model
Instrumental variable analysis
Mortality
All-cause
Cardiovascular
Sudden death
Unadjusted
Model
Hospitalization
Adjusted
Model
All-cause
Cardiovascular
CHF or fluid overload
0.70
0.80
0.90
1.00
0.70
0.80
0.90
1.00
1.10
Hazard Ratio (95% CI) per 30 min longer TT
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Figure 4
TT and all-cause mortality, by region
Hazard Ratio (95% CI)
(Ref.)
1.25
North
America
1.00
0.70
Europe/
ANZ
0.50
0.40
0.30
0.20
0.15
0.10
Japan
180 min
210 min
240 min
270-300 min
Treatment Time (minutes)
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
TT categories and intermediate
outcomes (1)
Table 3
Categorical TT (standard regression model)
180 min
210 min
240 min
270-300 min
-0.61 (-0.70,-0.52)
-0.21 (-0.29,-0.12)
0.00 (Ref.)
0.38 (0.28,0.47)
Pre-HD SBP (mmHg)
0.50 (-0.29,1.29)
0.45 (-0.31,1.22)
0.00 (Ref.)
0.21 (-0.67,1.09)
Post-HD SBP (mmHg)
1.32 (0.52,2.12)
0.38 (-0.40,1.15)
0.00 (Ref.)
-2.18 (-3.07,-1.28)
-0.24 (-0.29,-0.19)
-0.07 (-0.12,-0.02)
0.00 (Ref.)
0.19 (0.13,0.24)
Weight loss (kg)
Hemoglobin (g/dL)
Estimate (95% CI) shown is the difference in each outcome associated with prescribed treatment time
Models adjusted for DOPPS phase and country, age, sex, race, time on dialysis, BMI, 13 summary comorbid conditions,
residual kidney function, prescribed blood flow rate, and catheter use, and accounted for facility clustering.
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
TT categories and intermediate
outcomes (2)
Table 3
Categorical TT (standard regression model)
180 min
210 min
240 min
270-300 min
Albumin (g/dL)
-0.02 (-0.04,-0.01)
-0.01 (-0.03,0.01)
0.00 (Ref.)
0.05 (0.03,0.07)
WBC (1000/mL)
0.10 (0.02,0.19)
0.05 (-0.03,0.13)
0.00 (Ref.)
-0.06 (-0.15,0.03)
Ferritin (ng/mL)
-18.8 (-33.3,-4.3)
-15.6 (-29.0,-2.3)
0.00 (Ref.)
1.7 (-13.6,17.0)
Phosphorous (mg/dL)
0.05 (-0.01,0.11)
0.00 (-0.06,0.06)
0.00 (Ref.)
-0.03 (-0.09,0.04)
-0.11 (-0.13,-0.08)
-0.03 (-0.06,-0.01)
0.00 (Ref.)
0.10 (0.07,0.13)
Potassium (mEq/L)*
Estimate (95% CI) shown is the difference in each outcome associated with prescribed treatment time
Models adjusted for DOPPS phase and country, age, sex, race, time on dialysis, BMI, 13 summary comorbid conditions,
residual kidney function, prescribed blood flow rate, and catheter use, and accounted for facility clustering.
*Model also adjusted for dialysate K
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Continuous TT and intermediate
outcomes (1)
Table 3
Continuous TT
Standard regression model
Instrumental variable approach
(per 30 min)
(per 30 min)
Weight loss (kg)
0.26 (0.23,0.29)
-0.01 (-0.08,0.06)
Pre-HD SBP (mmHg)
-0.29 (-0.56,-0.01)
-1.35 (-2.09,-0.61)
Post-HD SBP (mmHg)
-1.01 (-1.28,-0.73)
-1.49 (-2.27,-0.70)
0.11 (0.09,0.13)
0.13 (0.08,0.19)
Hemoglobin (g/dL)
Estimate (95% CI) shown is the difference in each outcome associated with prescribed treatment time
Models adjusted for DOPPS phase and country, age, sex, race, time on dialysis, BMI, 13 summary comorbid conditions,
residual kidney function, prescribed blood flow rate, and catheter use, and accounted for facility clustering.
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Continuous TT and intermediate
outcomes (2)
Table 3
Continuous TT
Standard regression model
Instrumental variable approach
(per 30 min)
(per 30 min)
Albumin (g/dL)
0.02 (0.01,0.02)
0.05 (0.03,0.08)
WBC (1000/mL)
-0.04 (-0.07,-0.01)
-0.09 (-0.15,-0.03)
Ferritin (ng/mL)
6.7 (1.7,11.7)
17.7 (-2.4,37.8)
-0.04 (-0.06,-0.02)
-0.16 (-0.22,-0.11)
0.05 (0.04,0.06)
0.00 (-0.03,0.02)
Phosphorous (mg/dL)
Potassium (mEq/L)*
Estimate (95% CI) shown is the difference in each outcome associated with prescribed treatment time
Models adjusted for DOPPS phase and country, age, sex, race, time on dialysis, BMI, 13 summary comorbid conditions,
residual kidney function, prescribed blood flow rate, and catheter use, and accounted for facility clustering.
*Model also adjusted for dialysate K
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Figure 5
TT and achievement of clinical targets
Standard regression model
Instrumental variable analysis
Pre-HD SBP ≤ 140
mmHg
Post-HD SBP ≤ 130
mmHg
Hgb >11 g/dL
Phosphorous ≤ 5.5
mg/dL
Potassium ≤ 6
mEq/L*
0.80
*Model also adjusted
for dialysate K
0.90
1.00 1.10
1.25
0.90
1.00
1.10
1.25
Odds Ratio (95% CI) per 30 min longer TT
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Conclusions
• Favorable levels of a variety of clinical markers
may contribute to the better survival of patients
receiving longer TT.
• These findings support longer TT prescription in
the setting of in-center, three times per week HD.
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188
Acknowledgements
• Our thanks to DOPPS study coordinators, medical directors, and
participating patients for their dedicated work.
• The DOPPS would not be possible without the generous financial
support of the following companies who have demonstrated their
strong commitment to independent scientific research to improve
patient care:
–
–
–
–
–
–
Amgen (since 1996)
Kyowa Hakko Kirin (since 1999, in Japan)
Abbott Laboratories (since 2009)
Sanofi/Genzyme (since 2009)
Baxter Healthcare (since 2011)
Vifor Fresenius Medical Care Renal Pharma Ltd (since
2011)
• Support from DOPPS sponsors is provided without restrictions on
publications.
Tentori et al., Nephrol Dial Transplant 2012; 27: 4180-4188