Download
description
Transcript of Download
![Page 1: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/1.jpg)
Frequent Hemodialysis Network:Rationale for Studyand Study Design
National Kidney FoundationAnnual Meeting – April 2006
Michael V. Rocco, M.D., M.S.C.E.Wake Forest University School of Medicine
![Page 2: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/2.jpg)
Objectives
• Introduction• Selective review of data in daily and nocturnal
HD studies• Why a randomized trial is needed• FHN Nocturnal study
– Trial objectives and study design– Inclusion and exclusion criteria– Dose of dialysis– Primary and secondary outcomes– Baseline and follow-up period– Schedule of measurements
![Page 3: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/3.jpg)
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 1:33-42, 2006
![Page 4: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/4.jpg)
Review of Daily HD Trials through 5/31/05
• 14 cohorts of 268 unique patients– Largest cohort – 42 patients– One randomized design, using a randomized cross-
over trial– 13 observational studies
• All studies reported continuous outcomes between 3 and 24 months of follow-up, with the majority at 12 months
• Delivered treatment time or frequency reported in only 6 of 14 cohorts
![Page 5: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/5.jpg)
Daily HD – Summary of findings
Variable Outcome Number of 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
Suri R. et al. CJASN 1:33-42, 2006
![Page 6: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/6.jpg)
Milton Roy Model A
Built by Milton Roy Company of St. Petersburg, Florida in 1964
![Page 7: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/7.jpg)
Milton Roy Model A
Features:
Automatic hot water
Disinfection
Automatic alarm checks
Solid state logic
Acoustic tiles inside to reduce noise
![Page 8: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/8.jpg)
Nocturnal Home HD Machines
Aksys PHD System
Baxter Aurora Fresenius 2008K at home
![Page 9: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/9.jpg)
Nocturnal Home HD Programs in the U.S.
From www.HomeDialysisCentral.org
![Page 10: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/10.jpg)
Published data in Nocturnal HD Trials
• Systemic review of Nocturnal HD– Review of nocturnal HD publications from Medline,
Cochrane, BioAbstracts, Cinahl, Health Technology Assessment Database and Proceedings First
– 270 papers and abstracts screened– 71 publications retrieved for detailed review– Only 10 papers and 4 abstracts met inclusion criteria:
» Prescription of at least 5 nights per week and 6 hours per session
» Reported on at least one of four outcomes of interest» Follow-up of at least 4 weeks» Included a comparator group (case-control or pre/post within
patient comparison)
Walsh M et al. Kidney Int 67:1500-1508, 2005
![Page 11: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/11.jpg)
Review of Nocturnal HD Trials through 7/03
• 4 cohorts of unique patients– London, Ontario– Toronto, Ontario– Lynchburg, Virginia– Rochester, Minnesota
• Average follow-up time ranged from 6 weeks to 3.4 years
• Study sample sizes ranged from 5 - 63 Nocturnal patients
• No randomized trials• No comparative data on survival or occurrence of
cardiac events
![Page 12: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/12.jpg)
Nocturnal HD – Summary of findings
Variable Outcome Number of 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, 2006
+ Different tools and reporting methods used in individual studies
![Page 13: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/13.jpg)
Other reported improvements in patient outcomes with NHHD
• Improvement in sleep apnea (Hanly)• Increase in patient dry weight (McPhatter, Pierratos)• Decrease in serum creatinine level (McPhatter)• Decrease in beta-2 microglobulin levels (Raj)
Hanly PJ Pierratos A. NEJM 344: 102-107, 2001
Pierratos A et al. JASN 9:859-868, 1998
McPhatter LL et al. Adv Renal Replace Ther 6:358-365 1999
Raj DS et al Nephrol Dial Trans 15:58-64, 2000
![Page 14: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/14.jpg)
Nocturnal HD – Renal osteodystrophy
• Multiple studies with differing results– London, Ontario (Dr. Robert Lindsay)– Toronto, Canada (Dr. Andreas Pierratos)– Lynchburg, Virginia (Dr. Robert Lockridge)
![Page 15: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/15.jpg)
Serum phosphorus levels - London
p = NS; 2 nocturnal patients added phosphate to dialysate
Lindsay et al. Am J Kidney Dis 42(Suppl1) S24-S29, 2003
01
234567
89
0 6 12 18
Time in months
Serum phosphorus (mg/dl)
NocturnalControl
![Page 16: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/16.jpg)
Phosphate binder dosing - London
All patients prescribed calcium carbonate* p < 0.05 versus nocturnal HD group value; + p < 0.05 versus baseline value
Lindsay et al. Am J Kidney Dis 42(Suppl 1) S24-S29, 2003
-1000
0
1000
2000
3000
4000
5000
6000
7000
0 6*+ 12*+ 18
Time in months
Phosphate binder daily dose
(mg/day)
Nocturnal
Control
![Page 17: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/17.jpg)
Serum phosphorus and phosphate intake - Pierratos
Mucsi et al. Kidney Int. 53:1399-1404, 1998
0
1
2
3
4
5
6
7
8
9
-3 3 5
Time in months
Serum phosphorus (mg/dl)
0
200
400
600
800
1000
1200
1400
1600
Dietary phsophate intake
(mg/day)
Serum phosphorus
Phosphorus intake
![Page 18: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/18.jpg)
Serum phosphorus and phosphorus intake - Lockridge
McPhatter et al. Advances Renal Replacement Ther 6:358-365, 1999
0
2
4
6
8
10
12
-6 -3 3 6 12 18
Time in months
Serum phosphorus
(mg/dl)
0
200
400
600
800
1000
1200
1400
Dietary phsophate intake (mg/day)
Serum phosphrus
Phosphorus intake
![Page 19: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/19.jpg)
Phosphate binder dosing - Pierratos
*p < 0.05 versus baseline values pre-nocturnal HD;
Mucsi et al. Kidney Int 53:1399-1404, 1998
![Page 20: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/20.jpg)
Phosphorus binders - Lockridge
McPhatter et al. Advances Renal Replacement Ther 6:358-365, 1999
0
2
4
6
8
10
12
14
16
18
20
-6 -3 3 6 12 18
Time in months
Phosphate binders per day
Binders per day
![Page 21: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/21.jpg)
NHHD dialysis parameters
Parameter London Pierratos Lockridge
Machine F 2008 F 2008 F 2008
Time per treatment (hrs) 6 – 8 8 – 10 4 – 9
# of nights/week 5 – 6 6 5 – 6
Blood flow rate (ml/min) 200 – 300 200 - 300 200 – 250
Dialysate flow rate (ml/min)
300 300 – 350 200 – 300
# of needles Usually 1 2 2
Reuse No No Yes
![Page 22: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/22.jpg)
Gaps in knowledge in frequent HD
• Improvement in serum albumin level seen in some but not all frequent HD studies
• Hemoglobin levels have not improved in all frequent HD studies
• Effect of frequent HD on EPO requirements inconsistent
• Very small sample size does not allow for analysis of hospitalization rates or access complication rates
![Page 23: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/23.jpg)
Limitations of existing frequent HD studies
• Lack of adequate control groups– Most studies are pre-post case series reports
• Selection bias– Population different than typical in-center patients
• Dropout bias– Patients lost to follow-up may due worse than patients
who continue on nocturnal modality
• Publication bias– Negative studies less likely to be published
• Small sample size
![Page 24: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/24.jpg)
Advantages of a randomized trial
• A well-designed study of six times per week hemodialysis with rigorous methods for data collection and interpretation will help to alleviate the limitations of prior studies
• The preferred study design to minimize these limitations and biases is a randomized trial, analyzed in an intention to treat manner
![Page 25: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/25.jpg)
Frequent Hemodialysis Network
Nightly Hemodialysis
![Page 26: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/26.jpg)
Frequent Hemodialysis Network
• Sponsored by both NIH and CMS
• Clinical trials began in March 2006
• Comparison of standard three times per week hemodialysis with more frequent therapies– Daily in-center hemodialysis– Daily nocturnal home hemodialysis
![Page 27: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/27.jpg)
Trial Objectives – Feasibility and Safety
• Feasibility– Can we recruit and retain patients?
– Will patients adhere to dialysis six times per week?
– Why do patients become non-compliant to a six times per week prescription?
• Safety– Are there risks associated with daily HD?
![Page 28: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/28.jpg)
Trial objectives - Efficacy
• How will daily HD affect patient outcomes in:– Cardiovascular disease– Physical health– Mental health – Cognitive function– Nutrition– Blood pressure control– Anemia management– Phosphate management– Hospitalization and mortality
![Page 29: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/29.jpg)
Study timeline
0 6 12 18 24 30 36 42 48 54 60 66
Months
Study close-out
Patient follow-up
Patient enrollment
Training of studypersonnel
Protocoldevelopment
March 2006 May 2009
![Page 30: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/30.jpg)
Inclusion Criteria
• Patients with end stage renal disease requiring chronic renal replacement therapy
• Age – > 18 years (nocturnal HD)– > 12 years (daily in-center HD)
• Achieved mean eKt/V of > 1.0 over 2 baseline sessions
![Page 31: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/31.jpg)
Exclusion Criteria (1 of 2)• Residual kidney function (avoid confounding due
to residual renal function)– GFR greater than 10 ml/min/1.73 m2 (nocturnal HD)– Residual urea clearance > 3 ml/min per 35L urea volume
(daily in-center HD)• Reversibility of renal function• Life expectancy of less than six months• Unavailability for duration of study
– Scheduled for living donor kidney transplant – Change to peritoneal dialysis, or – Plans to relocate to an area outside of the referral area
of one of the clinical centers within the next 12/14 months
![Page 32: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/32.jpg)
Exclusion Criteria (2 of 2)• Less than 3 months since patient returned to
hemodialysis after renal transplantation• Medical history that might limit the individual’s ability to
take trial treatments for the 12/14 month duration of the study, including: – Currently receiving chemo or radiotherapy for a malignant
neoplastic disease other than localized non-melanoma skin cancer
– Active systemic infection (including tuberculosis, disseminated fungal infection, active AIDS but not HIV
– cirrhosis with encephalopathy
• Current pregnancy or planning to become pregnant within the next 12/14 months (patients require a higher dose of dialysis if pregnant).
![Page 33: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/33.jpg)
Nocturnal HD Study
• Prospective, randomized trial:– Three times per week in-center hemodialysis
versus– Six times per week nocturnal home hemodialysis
• Up to 250 chronic dialysis patients » 125 patients per study arm
• Follow-up of 14 months for each patient– Assumes training period of 2 months– At least 12 months of follow-up on nocturnal HD
therapy
![Page 34: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/34.jpg)
Clinical Centers for Nocturnal HD
Humber River Regional Hospital (Toronto) – Dr. Andreas Pierratos
Lynchburg Nephrology Associates (VA) – Dr. Robert Lockridge, Jr.
Rubin Dialysis Center, Saratoga Springs (NY) – Dr. Christopher Hoy
University of British Columbia – Dr. Michael CoplandUniversity of Iowa – Dr. John Stokes and Douglas SomersUniversity of Toronto – Dr. Chris ChanUniversity of Western Ontario – Dr. Robert LindsayWashington University – Dr. Brent Miller
![Page 35: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/35.jpg)
Dose of Dialysis• Nocturnal home hemodialysis
– Minimum prescription of 6 hours 6 times per week» Can decrease below this level if patient remains
hypophosphatemic despite the addition of 45 mmol/L of phosphorus to the dialysate
» Single or double needle hemodialysis» Minimum standardized Kt/V of 4.0
• Standard three times per week in-center HD– Equilibrated Kt/V of > 1.1
• In both arms of study, the specific dialysis dose is chosen by the patient’s nephrologist, as long as the minimum dose criteria above are met
![Page 36: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/36.jpg)
Dialysis Prescription for Nocturnal HD
• High flux dialyzers only• No reuse of dialyzers• Use of ultrapure dialysate• For patients performing two needle HD:
– Blood flow rate between 200 – 300 ml/min– Dialysate flow rate between 300 – 400 ml/min
• For patients performing single needle HD:– Blood flow rate between 500 – 600 ml/min– Dialysate flow rate between 300 – 400 ml/min
![Page 37: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/37.jpg)
Summary of Interventions
Parameter 3X week HD Nocturnal HD Difference
Sessions per week 3 6 + 100%
Hours per session > 2.5 hours 6 – 8 hours + 100%
Max time between HD sessions
68.5 hours 41 hours - 40%
Avg. interdialytic interval
52.5 hours 21.0 hours - 60%
Hours HD per week 10.5 40 + 281%
![Page 38: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/38.jpg)
Daily In-Center HD Study
• Prospective, randomized trial:– Three times per week in-center hemodialysis
versus
– Six times per week in-center hemodialysis
• Up to 250 chronic dialysis patients »125 patients per study arm
• Follow-up of 12 months for each patient
![Page 39: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/39.jpg)
Clinical Centers – Renal Research Institute
RRI – New York City (NY) – Dr. Nathan Levin
University of Western Ontario (London, Ontario) – Dr. Robert Lindsay
Washington University (MO) – Dr. Brent Miller
Vanderbilt University (TN) – Dr. Gerald Schulman
Wake Forest University (NC) – Dr. Michael Rocco
![Page 40: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/40.jpg)
Clinical Centers – UCSF
Univ. of California at San Francisco – Dr. Glenn ChertowUniv. of California, Davis – Dr. Thomas DepnerPeninsula (El Camino, San Jose) – Drs. John Moran and
George TingUniv. of California at Los Angeles – Drs. Allen
Nissenson, William Goodman and Isidro SaluskyUniv. of California at San Diego – Dr. Ravindra MehtaUniversity of Texas at San Antonio – Drs. Juan Ayus and
Steven Achinger
![Page 41: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/41.jpg)
Dose of Dialysis – Daily HD• Standard three times per week in-center HD
– Equilibrated Kt/V > 1.1
• Daily in-center HD– Six sessions per week– Minimum normalized eKt/V of 0.9 per session
» Normalized V = 3.271 × V 2/3
– Minimum time of 1.50 hours/treatment» Ensure minimum time for volume removal
– Maximum time of 2.75 hours/treatment» Assist with patient adherence to prescription
![Page 42: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/42.jpg)
Summary of Interventions
Parameter 3X week HD 6X week HD Difference
Sessions per week 3 6 + 100%
Hours per session > 2.5 hrs Median = 3.5
1.5 – 2.75 hrs
Median = 2.4
- 33%
Max time between HD sessions
68.5 hours 45.6 hours - 33%
Avg. interdialytic interval
52.5 hours 25.6 hours - 51%
Hours HD per week(5th – 95th percentile)
10.5
(9.0 – 13.1)
14.2
(11.5 – 16.5)
+ 35%
![Page 43: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/43.jpg)
Equilibrated Kt/V
1.7
0.92
1.39
0
0.5
1
1.5
2
2.5
Control Daily HD Nocturnal HD
eKt/V
-34% +22%
![Page 44: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/44.jpg)
Standardized Kt/V
Gotch F. Seminars in Dialysis 14: 15-17, 2001
![Page 45: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/45.jpg)
Efficiency of more frequent hemodialysis
0 to 60 minutes: BUN drops from 75 to 47 mg/dl
60 – 120 minutes BUN drops from 47 to 34 mg/dl
![Page 46: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/46.jpg)
Standardized Kt/V for Conventional HD
1.50
2.00
2.50
3.00
3.50
4.00
4.50
0.50 1.00 1.50 2.00
eKt/V
stdKt/V
GFR
15
12
9
6
3
0
Gotch F, FHN analysis
HEMO StudyStandard Arm
HEMO StudyHigh Dose Arm
![Page 47: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/47.jpg)
Standardized Kt/V for Daily HD
3.00
4.00
5.00
6.00
7.00
0.50 1.00 1.50 2.00
eKt/V
stdKt/V
GFR 0 GFR 3 GFR 6 GFR 9 GFR 12 GFR 15
Short Daily HD Dose Range
GFR1512 9 6 3 0
![Page 48: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/48.jpg)
Standardized Kt/V for Nocturnal HD
3.00
4.00
5.00
6.00
7.00
0.50 1.00 1.50 2.00
eKt/V
stdKt/V
GFR 0 GFR 3 GFR 6 GFR 9 GFR 12 GFR 15GFR1512 9 6 3 0
Long Nocturnal HD Dose Range
![Page 49: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/49.jpg)
Standardized (weekly) Kt/V
5.12
3.82
2.46
0
1
2
3
4
5
6
7
Control Daily HD Nocturnal HD
sKt/V
+55% +108%
![Page 50: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/50.jpg)
Phosphorus removal
299415
1218
0
200
400
600
800
1000
1200
1400
1600
Control Daily HD Nocturnal HD
Phosphate removal (mg/day) +39%+328%
![Page 51: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/51.jpg)
Beta-2-microglobulin clearance
9.03
4.884.73
0
2
4
6
8
10
12
Control Daily HD Nocturnal HDEquivalent B2 microglobulin clearance
(ml/min)
+ 3%+39%
+91%
![Page 52: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/52.jpg)
Study Outcomes
• Insufficient power to perform a mortality analysis– Need more than 1000 patients
• Insufficient power to perform an analysis of hospitalization rates– Need for more than 600 patients to detect a
25% decrease in hospitalization rates
![Page 53: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/53.jpg)
Primary Outcomes
• Composite endpoints:– Change in LV mass as measured by
cardiac MRI or death
– Change in RAND Physical Health Composite (PHC) score from the SF-36 or death
![Page 54: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/54.jpg)
LV mass and Outcomes• LVH is a potent marker of cardiovascular death
risk in patients with ESRD– By Cox proportional hazards modeling, each 1.0 g/m2
increase in LV mass was associated with a » 1% increase in all-cause death or » 1% increase in cardiovascular death [Zoccali]
– By Cox modeling, a 10% decrease in LV mass was asssociated with a
» 22% decrease in all-cause mortality» 28% decrease in cardiovascular mortality [London]
Zoccali C et al. J Am Soc Nephrol 12: 2768-2774, 2001London GM et al. J Am Soc Nephrol 12: 2759-2767, 2001
![Page 55: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/55.jpg)
PCS score and outcomes in DOPPS
N = 10,030 patients
Minimum of 6 months F/U
Mapes DL et al. Kidney Int 64: 339-349, 2003
![Page 56: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/56.jpg)
PCS score and outcomes in Fresenius database
– 13,592 prevalent dialysis patients– 6 month observation period– Odds ratio for death in multivariate model:
» 0.98 for each 1 point increase in PCS score» 0.98 for each 1 point increase in MCS score
Lowrie EG et al. Am J Kidney Dis 41: 1286-1292, 2003
![Page 57: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/57.jpg)
Secondary Outcomes
Outcome domain Main secondary outcome
Depression Change in Beck Depression Index
Nutritional status Change in serum albumin level
Cognitive function Change in Trailmaking Test B
Mineral metabolism Change in pre-HD phosphorus level
Hypertension Review of BP level and medications
Anemia Review of hemoglobin level, ESA dose and iron parameters
Clinical events Rates of death and hospitalizations
![Page 58: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/58.jpg)
Other measures (slide 1 of 2)• Cardiovascular
– Cardiac deaths and hospitalizations– Interdialytic weight gains
• Cognitive function– Modified mini mental status exam
• Physical functioning– Lower extremity performance battery
» Gait speed» Timed chair stands» Standing balance
![Page 59: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/59.jpg)
Other measures (slide 2 of 2)• Kinetic modeling for
– Phosphate– Creatinine 2-microglobulin
• Quality of life– SF-36– Health Utilities Index (QALY)
• Nutrition and inflammation– Bioimpedance– Protein catabolic rate– C reactive protein levels
• Economic
![Page 60: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/60.jpg)
Steering Committee• Chair
– Dr. Alan Kliger, Yale University (CN)
• NIDDK representatives– Dr. Paul Eggers– Dr. Robert Star
• Data Coordinating Center– Dr. Gerald Beck, Cleveland Clinic (OH)
• In-center HD Coordinating Center PIs– Dr. Nathan Levin, Renal Research Institute (NY)– Dr. Glenn Chertow, Univ. of California at San Francisco
• Nocturnal HD Coordinating Center PI– Dr. Michael Rocco, Wake Forest Univ. (NC)
![Page 61: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/61.jpg)
Grant support• National Institutes of Health ($16 million)
– Data Coordinating Center– Nine clinical centers and the Clinical Coordinating
Center– Funding for additional dialyzers and for training for
patients who do not have Medicare as primary insurer
• Centers for Medicare and Medicaid ($1.5 million)– Additional reimbursement for training of 75 home
nocturnal HD patients– Additional reimbursement for 4th treatment per week
for 75 home nocturnal HD patients and 75 daily in-center patients
![Page 62: Download](https://reader033.fdocuments.in/reader033/viewer/2022061212/549600d8b479596b078b458d/html5/thumbnails/62.jpg)
FHN grant support