Daily and Nocturnal Hemodialysis

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Daily and Nocturnal Hemodialysis

• Alan S. Kliger MD
• Hospital of St. Raphael
• Yale University School of Medicine
• New Haven CT

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Best Opportunities to Improve Outcomes

• Increase Dialysis Dose
• Reduce Inflammation
• Decrease LVH
• Restore fluid balance and BP
• Reduce Sympathetic Activity
• Reduce Depression

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Cardiovascular disease mortalitygeneral
population vs ESRD patients
Annual CVD Mortality ()
Dialysis Female
Dialysis Black
Dialysis White
Age (years)
Foley RN, et al. Am J Kidney Dis.
199832S112-S119.
GP General Population.
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4
5
5
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HEMO Study Survival by dose group
1,846 Patients
Eknoyan et al, N Eng J Med 2002
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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
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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)

Separation in Std Kt/V in HEMO Trial
Only 16 difference in mean Std Kt/V between
dose groups
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Effect of increasing length of dialysis Three
sessions per week
7
6
5
HEMO High
4
Weekly Dialysis Dose (stdKt/V)
3
2
1
HEMO Standard
0
0.0
0.5
1.0
1.5
Dialysis dose each dialysis (eKT/V)
10
Effect of increasing number of dialysis sessions
per week
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Hemodialysis
Daily Dialysis
6
sessions/wk
6
5
HEMO High
4
Weekly Dialysis Dose (stdKt/V)
3
3
2
1
HEMO Standard
0
0.0
0.5
1.0
1.5
Dialysis dose each dialysis (eKT/V)
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Published data in Daily HD Trials

• Systemic review of daily HD
• Review of daily HD publications in 6 languages
• More than 800 citations screened
• 233 full text articles retrieved for detailed
  review
• Only 25 articles met the inclusion criteria
• Five or more adult patients
• Follow-up of at least 3 months
• Prescription of 1.5 3 hours 5 7 days/week
• Published after 1989
• Suri R et al. CJASN 133-42, 2006

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Daily HD Summary of Findings
Variable Outcome studies
SBP or MAP Decrease 10 of 11
Serum phosphorus or binder dose No change 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
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Suri R. et al. CJASN 133-42, 2006
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Retrospective Analysis of Survival for 415
Patients Treated with Short Daily Hemodialysis

• 10 year survival 429
• 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 233283, 2008
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C U M S U R V I V A L
SHORT DAILY HOME HD N265
USRDS CAD TX 2005
USRDS PD AND HD SURVIVAL
Slide courtesy of Dr. Kjellstrand
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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 671500-1508, 2005

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Walsh M et al Kidney Int 67 1500-1508, 2006
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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 2981291, 2007
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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 (n44) 15.3,
  CI (1.0, 29.6 )
• Observed data only (n35)
  19.7, CI (1.9, 37.4 )

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Culleton et al JAMA 2981291, 2007
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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 1.270.06 to 2.230.09
• Phosphorus and PTH levels fell
• BP and BP medications fell

Chan JASN Express Dec 17 2008
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Nocturnal Home Hemodialysis (NHHD)

• Hb rose from 11.30.3 to 12.50.4 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
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Frequent Hemodialysis Network

• 2 parallel RCT
• Comparing in-center 6x/wk dialysis to
  conventional 3x/wk dialysis
• Comparing home nocturnal 6x/wk dialysis to
  conventional 3x/wk home dialysis

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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.
1.5 months training 12 months 6x/Week Nocturnal
HD
12 months 3x/Week Conventional Home HD
12 months 6x/Week Daily In-center HD
12 months 3x/Week Conventional In-center HD
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Standard weekly Kt/V urea
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Phosphorus removal
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Beta-2-microglobulin clearance
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Co-Primary Outcomes

• Composite of 1-year mortality and change in LV
  mass by cardiac cine-MRI
• Composite of 1-year mortality and change in RAND
  PHC from SF- 36

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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
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Clinical Centers for Daily TrialRRI 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
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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
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Randomized Subjects

• Daily Nocturnal
• Goal 250 90
• Enrolled 378 118
• Randomized 245 81

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Trial Timelines

• Daily Nocturnal
• Randomization Ends 3/2009 5/2009
• Study Period Ends 3/2010 5/2010
• Report Results late 2010-2011

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Cost-Effectiveness of Frequent in-Center
Hemodialysis

• Monte Carlo simulation model
• Inputs
• Various frequencies and duration of HD (3-6x/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 191792, 2008
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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 lt 125,000/ life
  year gained

Lee CO et al JASN 191792, 2008
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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 191792, 2008
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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 191792, 2008
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In-Center Nocturnal HD (INHD)

• 16 patients in New Haven switched from
  conventional to INHD
• Kt/V urea rose from 1.20.16 to 2.60.65
• UF rate fell from 10.34.5 to 5.91.7 mL/hr/kg
• Phosphorus fell from 5.31.3 to 4.41.1mg/dL
• No change in psychosocial assessments (QoL)

Troidle Adv Chronic Kid Dis 14244,2007
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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
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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
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Frequent HD in USA Current Status
DaVita FMC Satellite
Home (O RCG)
3x/wk 70 163 5
QOD 17 33 2
4x/wk 50 8 6
5x/wk 696 6 39
6x/wk 764 3 88
7x/wk 5 1 0
INHD 842 785 10
PD 9,207 7,921 648
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NxStage Growth 2004 to 2008
Courtesy Dr Lockridge
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International Quotidian Dialysis Registry

• Standard Daily HD gt2 hrs, 5-7x/wk
• Nocturnal HD gt 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
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Table 1 Baseline Patient Characteristics
Nocturnal/Long HD (n2330) Short-daily HD (n367) Limited-care CHD (n5531)

Female Female 1725 (74) 231 (63) 3286 (59)
Age at RRT Age at RRT 44.5 14.1 (3 - 102) 47.4 17.4 (7 - 91) 60.3 15.6 (18 - 94)
Age at QD Age at QD 50.3 12.8 (18 - 102) 50.3 12.3 (18.8 - 90.0) -
Vintage Vintage 4.3 5.5 (0 - 36.3) 4.4 5.5 (0 28.9) 3.5 4.9 (0 - 34.5)
Race Race
Caucasian 1356 (58) 248 (68) 4483 (81)
Black 675 (29) 57 (16) 663 (12)
Other 698 (13) 61 (16) 384 (7)
Vascular access Vascular access
Catheter 559 (28) 115 (37) 1405 (27)
Graft 289 (15) 34 (11) 766 (15)
Fistula 1145 (59) 160 (52) 3092 (58)
Country Country
Australia/NZ 1071 (46) 139 (38) 506 (9)
Canada 140 (6) 85 (23) 212 (4)
United States 1118 (48) 142 (39) 607 (11)
Other - - 3112 (76)
IQDR 2009
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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

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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

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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