Transcript Frequent Hemodialysis Network: NIH/CMS Daily and Nocturnal

Daily and Nocturnal
Hemodialysis
Alan S. Kliger MD
Hospital of St. Raphael
Yale University School of Medicine
New Haven CT
Best Opportunities to Improve
Outcomes
Increase Dialysis Dose
Reduce Inflammation
Decrease LVH
Restore fluid balance and BP
Reduce Sympathetic Activity
Reduce Depression
Cardiovascular disease mortality
general population vs ESRD patients
Annual CVD Mortality (%)
100
10
GP Male
1
GP Female
GP Black
GP White
0.1
Dialysis Male
Dialysis Female
Dialysis Black
0.01
Dialysis White
0.001
25-34
35-44
45-54
55-64
66-74
75-84
>85
Age (years)
GP = General Population.
Foley RN, et al. Am J Kidney
Dis. 1998;32:S112-S119.
4
5
HEMO Study: Survival by dose group
1,846 Patients
Eknoyan et al, N Eng J Med 2002
BREAST
CANCER
HIV
PROSTATE
CANCER
THE DEATH-RATE
WAS THREE TIMES
THAT OF BREAST
CANCER AND HIV,
TWICE THAT OF
PROSTATE CANCER
Slide courtesy of
Dr. Kjellstrand
HEMO
Post-Hoc Analysis of HEMO
Study
Limited separation between treatment groups for unified
dose measures, such as
Standard Kt/V ≅ [urea generation rate] / [average (C0)]
Weekly Std Kt/V
Separation in Std Kt/V in HEMO Trial
Mean = 2.19
Mean = 2.53
2.88
2.59
2.30
2.02
Standard
Dose
High
Dose
Only 16% difference
in mean Std Kt/V
between dose groups
Weekly Dialysis Dose (stdKt/V)
Effect of increasing length of dialysis
Three sessions per week
7
6
5
HEMO: High
4
3
2
1
0
0.0
HEMO: Standard
0.5
1.0
Dialysis dose each dialysis (eKT/V)
1.5
Weekly Dialysis Dose (stdKt/V)
Effect of increasing number of
dialysis sessions per week
7
6
Hemodialysis
sessions/wk
Daily
Dialysis
6
5
HEMO: High
4
3
3
2
1
0
0.0
HEMO: Standard
0.5
1.0
1.5
Dialysis dose each dialysis (eKT/V)
Daily HD – Summary of Findings
Variable
Outcome
# studies
SBP or MAP*
Serum phosphorus or binder
dose*
Decrease
No change
10 of 11
6 of 8
Anemia (Hb, HCT or EPO dose)
Improvement
7 of 11
Serum albumin
Increase
5 of 10
HRQOL
Improvement
6 of 12
Vascular access dysfunction
No change
5 of 7
Suri R. et al. CJASN 1:33-42, 2006
12
Retrospective Analysis of
Survival for 415 Patients Treated
with Short Daily Hemodialysis
• 10 year survival: 42+9%
• Compared with matched patients from
USRDS:
– Daily dialysis patient survival was 2-3 times
higher
– Predicted survival times were 2.3 -10.9 yrs
longer for daily dialysis patients
Kjellstrand et al NDT 23:3283, 2008
100
C
U
M
S
U
R
V
I
V
A
L
75
SHORT DAILY
HOME HD
N=265
USRDS
CAD TX
2005
50
25
USRDS
PD AND HD
SURVIVAL
0
0
5
10
Slide courtesy of Dr. Kjellstrand
15
YEAR
20
25
Nocturnal HD – Summary of
Findings
Variable
Outcome
# studies
SBP or MAP*
Decrease
4 of 4
Number of antihypertensives*
Decrease
4 of 4
Serum phosphorus or binder dose
No change
1 of 2
Anemia (Hb, HCT or EPO dose)*
Improvement
3 of 3
HRQOL
Improvement
Variable+
Walsh M et al. Kidney Int 67:1500-1508, 2005
Walsh M et al Kidney Int 67: 1500-1508, 2006
15
Alberta RCT Nocturnal HD vs
Conventional HD
•
•
•
•
Primary Outcome: Change in LV mass
52 patients randomized
44 had baseline MRI
35 had follow-up MRI after 6 months
– No second MRI
• 6 refused
• 2 transplanted
• 1 died
Culleton et al JAMA 298:1291, 2007
16
Result: LV Mass Gm (SD)
Conventional
HD
Nocturnal
HD
Baseline
181.5 (92.3)
177.4 (51.1)
Exit
183.0 (84.2)
163.6 (45.2)
Change
1.5 (24.0)
-13.8 (23.0)
Estimated Treatment Effect on LV Mass (Gm)
Last observation carried forward (n=44): 15.3, CI (+1.0, +29.6 )
Observed data only (n=35):
19.7, CI (+1.9, +37.4 )
Culleton et al JAMA 298:1291, 2007
17
Nocturnal Home Hemodialysis
(NHHD)
Nocturnal Hemodialysis Improves
Erythropoietin Responsiveness and
Growth of Hematopoietic Stem Cells
– 16 patients switched from conventional HD
to NHHD
– Kt/V urea increased from 1.27+0.06 to
2.23+0.09
– Phosphorus and PTH levels fell
– BP and BP medications fell
Chan JASN Express Dec 17 2008
Nocturnal Home Hemodialysis
(NHHD)
– Hb rose from 11.3+0.3 to 12.5+0.4 Gm/dL
with no change in EPO or iron
– Cell culture studies and gene profiling
showed up regulation of genes responsible
for hematopoetic progenitor cells after
more intensive HD.
– NHHD increases growth and production of
RBCs.
Chan JASN Express Dec 17 2008
Frequent Hemodialysis Network
2 parallel RCT
1. Comparing in-center 6x/wk dialysis to
conventional 3x/wk dialysis
2. Comparing home nocturnal 6x/wk
dialysis to conventional 3x/wk home
dialysis
FHN Study Designs
Daily In-Center
Patients from 10
regional centers
Nocturnal
Patients from 9
regional centers
250 pts
randomized
over 46 mo.
90 pts
randomized
over 27 mo.
12 months
6x/Week
Daily
In-center HD
12 months
3x/Week
Conventional
In-center HD
Compare outcomes
after 1 year
1.5 months
training +
12 months
6x/Week
Nocturnal HD
12 months
3x/Week
Conventional
Home HD
Compare outcomes
after 1 year
Standard weekly Kt/V urea
7
6
5.12
sKt/V
5
3.82
4
3
2.46
2
1
+55%
+108
0
3X w eek HD
Daily HD
Nocturnal HD
22
Phosphorus removal
Phosphate removal (mg/day)
1600
1400
1218
1200
1000
800
600
400
415
299
+39%
200
+328%
0
3X week HD
Daily HD
Nocturnal HD
23
Equivalent B2 microglobulin clearance
(ml/min)
Beta-2-microglobulin clearance
12
10
9.03
8
6
4.88
4.73
4
2
+ 3%
+91%
Daily HD
Nocturnal HD
0
3X week HD
24
Co-Primary Outcomes
• Composite of 1-year mortality and
change in LV mass by cardiac cineMRI
• Composite of 1-year mortality and
change in RAND PHC from SF- 36
25
9 Main Outcome Domains
#
Domain
Main Outcome
1
Cardiovascular structure /
Function
 LV mass by cardiac MRI
2
Health related QOL /
Physical function
 SF-36 Physical Health Composite
3
Depression / Burden of illness
 Beck Depression Index
4
Cognitive function
 Trail Making B Score
5
Nutrition/Inflammation
 Serum Albumin
6
Mineral metabolism
 Serum Phosphorus
7
Survival / Hospitalization
Non-Access Hospitalization/Death
Rate
8
Hypertension
Several outcomes
9
Anemia
Several outcomes
Clinical Centers for Daily Trial
RRI and UCSF/Stanford Cores
Univ. of Western Ontario
– Dr. Robert Lindsay
Washington Univ. (MO)
-- Dr. Brent Miller
RRI: New York City (NY)
– Dr. Peter Kotanko
Vanderbilt University (TN)
– Dr. Gerald Schulman
Wake Forest University (NC)
– Dr. Michael Rocco
UCSF/Stanford
– Dr. Glenn Chertow
Univ. California, Davis
– Dr. Thomas Depner
Peninsula Dialysis: (CA)
– Dr. George Ting
UCLA
– Dr Anjay Rastogi
UCSD
– Dr. Ravindra Mehta
27
Clinical Centers for Nocturnal
Trial
Univ. of British Columbia
– Dr. Michael Copland
Humber River Hosp
– Dr. Andreas Pierratos
University of Toronto
– Dr. Chris Chan
Univ. of Western Ontario
– Dr. Robert Lindsay
Rubin Dialysis (NY)
– Dr. Christopher Hoy
University of Iowa
– Dr. John Stokes
Lynchburg Nephrology
– Dr. Robert Lockridge Jr.
Wake Forest University
– Dr. John Burkart
Washington University
– Dr. Brent Miller
Randomized Subjects
Daily
Nocturnal
Goal
250
90
Enrolled
Randomized
378
245
118
81
Trial Timelines
Daily
Nocturnal
Randomization Ends 3/2009
5/2009
Study Period Ends
5/2010
Report Results
3/2010
late 2010-2011
Cost-Effectiveness of Frequent
in-Center Hemodialysis
• Monte Carlo simulation model
• Inputs:
– Various frequencies and duration of HD (36x/wk, 2-4.5 hrs/session)
– Outcomes: costs, life expectancy, QALY
– Assumptions on potential effects of
frequent dialysis on outcomes –
(ex: 32% reduction in mortality with
6x/wk)
Lee CO et al JASN 19:1792, 2008
Cost-Effectiveness of Frequent
in-Center Hemodialysis
• Incremental cost-effectiveness ratio will
be at least $75,000/ life year gained
• None of the strategies using 6x/wk HD
achieved a cost-effectiveness ratio of
< $125,000/ life year gained
Lee CO et al JASN 19:1792, 2008
Cost-Effectiveness of Frequent
in-Center Hemodialysis
How could costs “break even”?
• If the per-session costs were reduced
between 32 and 43%
• Reduction in hospitalization rate
– For 4 HD/wk, need to reduce
hospitalization to 46% of current rate
– For 5 HD/wk, need to eliminate
hospitalizations
Lee CO et al JASN 19:1792, 2008
Cost-Effectiveness of Frequent
in-Center Hemodialysis
Conclusions
• More frequent in-center HD strategies
would likely increase ESRD program
costs considerably.
• Transition to home-based therapies will
be required to derive any benefit that
might be present without incurring
excessive costs.
Lee CO et al JASN 19:1792, 2008
In-Center Nocturnal HD (INHD)
• 16 patients in New Haven switched from
conventional to INHD
–
–
–
–
Kt/V urea rose from 1.2+0.16 to 2.6+0.65
UF rate fell from 10.3+4.5 to 5.9+1.7 mL/hr/kg
Phosphorus fell from 5.3+1.3 to 4.4+1.1mg/dL
No change in psychosocial assessments (QoL)
Troidle Adv Chronic Kid Dis 14:244,2007
In-Center Nocturnal HD (INHD)
• 39 patients in Toronto switched from
conventional to 8 hr INHD
–
–
–
–
–
URR increased from 74% to 89%
Phosphorus fell from 5.9 to 3.7 mg/dL
Number of antihypertensive drugs: 2.0 to 1.5
ESA use fell significantly
QoL, sleep, intradialytic cramps, appetite,
energy level all improved significantly
Bujega CJASN April 2009
In-Center Nocturnal HD (INHD)
• 224 pts in Turkey switched from
conventional to 8 hour INHD
– Compared prospectively with matched cohort
224 pts on conventional 4 hour HD 3 days/wk
– INHD patients had
•25% hospitalization rate
•78% reduction in mortality
•Less intradialytic hypotension,
lower phosphate, reduced
arterial stiffness
•Improved cognitive function
Ok E: ASN abstract F-FC-317 2008
Frequent HD in USA:
Current Status
DaVita
FMC*
Satellite
Home
3x/wk
70
(O RCG)
163
5
QOD
4x/wk
17
50
33
8
2
6
5x/wk
696
6
39
6x/wk
7x/wk
764
5
3
1
88
0
842
9,207
785
7,921
10
648
INHD
PD
NxStage Growth 2004 to 2008
4000
3100
3000
2223
NxStage Daily Patients
2000
NxStage HT Centers
1022
1000 45 295
8
70
174
334
400
0
2004 2005 2006 2007 2008
Courtesy Dr Lockridge
International Quotidian Dialysis
Registry
• Standard Daily HD: >2 hrs, 5-7x/wk
• Nocturnal HD:
> 6 hrs, 3-7x/wk
• Enrollment as of Mar, 2009:
US
1,260
ANDATA 1,210
Canada
225
Total
2,695
Nesrallah GE, on behalf of the quotidian
dialysis international working group
Conclusions
• More intensive dialysis is needed to
improve ESRD patient outcomes
• Observational trials suggest better
anemia care, phosphorus control, fluid
and BP management with intensive HD
• Retrospective analysis shows improved
survival with intensive dialysis
Conclusions
• Frequent in-center HD (4-6 HD/wk) is
more costly - unless per-treatment HD
costs fall
• Frequent home HD (4-6HD/wk) is
increasing slowly
• NHHD is promising, but utilized by few
patients
• INHD is the fastest growing – in US and
internationally - with more efficient use
of facility space improving financial
viability
Conclusions
• RCT of NHHD and daily in-center HD in
progress
• International Quotidian Dialysis Registry
may give us meaningful information on
the effect of intensive HD on mortality
and hospitalization