The New Dialysis Patient
Lawrence Kleinman, MD
ANNA Spring Conference
Chateau Briand, Carle Place, NY
May 23,2012
Resources
•ASN Renal Weekends 2011
Long Interdialytic Interval and Mortality among Patients Receiving
Hemodialysis http://www.nejm.org/doi/abs/10.1056/NEJMoa1103313
R. N. Foley and Others| September 22, 2011 | N Engl J Med 365:1099
Hemodialysis http://www.nejm.org/doi/abs/10.1056/NEJMra0902710
J. Himmelfarb and T. A. Ikizler| November 4, 2010 | N Engl J Med
363:1833
A Randomized, Controlled Trial of Early versus Late Initiation of Dialysis
http://www.nejm.org/doi/abs/10.1056/NEJMoa1000552
B. A. Cooper and Others| August 12, 2010 | N Engl J Med 363:609 CME
The Initiation of Renal-Replacement Therapy — Just-in-Time Delivery
http://www.nejm.org/doi/abs/10.1056/NEJMe1006669
N. Lameire and W. V. Biesen| August 12, 2010 | N Engl J Med
363:678
“THE STANDARD”
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Fistula
Kt/V
EPO – Hgb ? - 11
B/P control with meds
Sodium modeling
Early Start
Everyone Start
Routine Treatment
Original Article
A Randomized, Controlled Trial of Early versus
Late Initiation of Dialysis
Bruce A. Cooper, M.B., B.S., Ph.D., Pauline Branley, B.Med., Ph.D., Liliana
Bulfone, B.Pharm., M.B.A., John F. Collins, M.B., Ch.B., Jonathan C. Craig, M.B.,
Ch.B., Ph.D., Margaret B. Fraenkel, B.M., B.S., Ph.D., Anthony Harris, M.A., M.Sc.,
David W. Johnson, M.B., B.S., Ph.D., Joan Kesselhut, Jing Jing Li, B.Pharm., B.Com.,
Grant Luxton, M.B., B.S., Andrew Pilmore, B.Sc., David J. Tiller, M.B., B.S., David C.
Harris, M.B., B.S., M.D., Carol A. Pollock, M.B., B.S., Ph.D., for the IDEAL Study
In this study, adults with progressive chronic kidney disease and an
estimated glomerular filtration rate between 10 and 15 ml per
minute per 1.73 m2 (stage V chronic kidney disease) were randomly
assigned to early or late initiation of dialysis.
Early initiation of dialysis was not associated with an improvement in
survival or clinical outcomes.
New England J Med
Volume 363(7):609-619
August 12, 2010
Enrolment, Randomization, and Follow-up
Cooper BA et al. N Engl J Med 2010;363:609-619
Timing at the Start of Dialysis
100
Avg 7ml/min
90
25,901
incident adult
HD patients
from the
Canadian
Organ
Replacement
Register
(CORR)
80
Avg 15ml/min
70
60
P < 0.05
50
40
30
20
10
0
0
3
6
9
12
15
18
21
24
27
Time from dialysis start
Clark et al, CMAJ, 2010
30
33
36
Survival by age at start of dialysis across DOPPS regions.
Canaud B et al. CJASN 2011;6:1651-1662
©2011 by American Society of Nephrology
Arteriovenous Fistula
National sample: FMC database all incident patients (2007)
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AVF:AVG=3:1 ratio (6365:1916)
*fistula’s placed earlier than grafts
*patients with AVG are older, female, black, with diabetes
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Mature AVG- median time to failure 119 days
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Mature AVF –median time to failure 87 days
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Catheters removed from :71% of mature grafts
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59% of mature fistulas
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AVG matured twice as fast than AVF (49 days vs 119 days)
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Note:
Surgical quality of access need to be examined more closely.
Delays in access maturation requires prompt attention.
80
70
60
50
AVF
AVG
40
30
20
10
0
Mature
Failed
Kaplan–Meier Curves for the Time to Catheter Malfunction, According to
Study Group.
Hemmelgarn BR et al. N Engl J Med 2011;364:303-312.
ADEQUACY
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IF ANY MAJOR ORGAN WERE TO BE
“SHUT DOWN” & REPLACED WITH
INTERMITTENT FUNCTION, WOULD
THAT EVER BE “ADEQUATE”?
Think beyond Kt/V
One size DOES NOT fit all!
TIME
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Important in terms of adequacy – “the
driving” component of Kt/V
Equally, if not, MORE important in
terms of volume control
Ultrafiltration rate: amount of UF/time
The higher the UF rate, the higher the
associated mortality rate!
Summary of Observational Studies comparing outcomes associated
with short and long term hemodialysis treatment time
Clinical Journal of the American Society of Nephrology
Modifiable treatment Practices and
sudden death
Association of longer treatment time with
lower mortality and hospitalizations
Patient model
Facility model
All-cause mortality
Cardiovascular death
Sudden death
Any hospitalization
Hospitalization due to CHF
Or fluid overload
0.80
0.90
1.00
1.10
0.80
HR per 30 minutes longer (95% Cl)
N=37,414 patients from DOPPS 1-3
0.90
1.00
1.1
Pathogenesis of LVH
Traditional
risk
factors
Non-traditional
Risk factors
unknown
Pump Abnormalities
Cerebrovascular
Left Ventricular hypertrophy
(LVH)
Peripheral Vascular
Disease
disease
Cardiovascular
Disease
Conduction Abnormalities
Coronary Heart Disease
LVH Central Role in Dialysis Care
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CKD/ESRD
ECFV
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Other
LVH
factors
SBP
Cardiac Fibrosis
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LVH progresse with
severity and duration of
CKD
But:
10% reduction in LVMI in
ESRD is associated with:
*22% in all causes
*28% in CV mortality
Sudden cardiac death
dilated cardiomyopathy and CHF
Ischemic heart disease
stroke
4d trial-Krane Vet.al CJASN,2009
London GM, et al JASN,2001
The predominant cause of LVH is not poor
medical control of hypertension,but poorly
managed extra-cellular volume expansion
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Our concept of dry weight is killing
more patients than al of the angst
about kt/v,pth,hgb,p,lipids…..
The serious Inter and Intra-dialytic
Impact of Excess ECVF + Sodium
Volume Overload
HTN
LVH
CV Events
THE IMPORTANCE OF DRY WEIGHT
AND HOW TO MEASURE IT
Agarwal R,Et’al Am J Med 2003
MORTALITY
Impact of Fluid Overload on survival
Hazard
Ratio
P
value
Age (1 year)
1.06
<0.001
Dialysis
vintage
(1/year)
0.999
0.052
Diabetes
(y/n)
1.6
0.03
IDWG
0.9
Fluid overload
(<2,5L)
2.6
1.0
survival
Variable
0.5
0.002
265 patients;7year follow up; all cause mortality
Fluid overload of>2,5 l is linked to a dramatic HR
Wiseman nephrol Dial Transplant,2009
FO<2.5 L
0.8
0.6
0.4
0.2
0.0
FO>2.5 L
0
20
40 60
80 100
Time (months)
What BP Target
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Use home BP measures to guide tx goal BP
-home systolic BP linked to mortality
-Best home SBP 120-130 mmHg
-Best ambulatory systolic is 110-120mm Hg
Use dialysis unit BP measure to guide tx
prescription
Individualize according to co-morbidity
Blood Pressure and Salt in Hemodialysis
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Conclusions:
Require reductions in both dietary &
intradialytic Na+ influx to:
Lead to reduction in IDWG
Improve intradialytic hemodynamic
stability
Reduce antihypertensive medication
burden
BP Control
Volume Control
BP control
 Get dry weight
 Add oral furosemide
 Rigorous NaCl control in the interdialytic interval;
 Eliminate Na+modeling; lowering Dialysate Na+
RAS control
 Add low dose ACE/ARB
 Consider prophylactic carvedilol
ESTIMATED DRY WEIGHT
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reflects patient’s ability to tolerate a given
amount of Ultrafiltration over a given amount
of time.
considered as a way of managing HTN and
reducing anti-hypertensive medications
Clear lungs and lack of edema NOT indicative
of achieving EDW
Alternative methods for improving accuracy –
ex:Hematocrit lines, Bioimpendance
2.5
Impact of Ultrafiltration Rate
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Post-hoc analysis
Mortality
All
CV
Outcomess: all cause and
CV mortality
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Risks of all-cause and CVrelated mortality begin to
increase at rates >10ml/h/kg
1.8
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3h
4h
1.6
UFR considered at baseline
1.4
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70 kg patient with 3K IDWG
1.2
HEMO Study data (N=1,846)
Adjusted hazard ratio
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2
Associations between UFR and CV and all-cause mortality
1
CV mortality
All-cause mortality
5
10
15
UFR (ml/hr/kg)
Flythe, et al. Kidney Int; 79:250-257;2011
20
SODIUM
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Ideally, dialysate sodium should be slightly
lower, than the patient’s sodium level
Currently, sodium is viewed more as a way
to stabilize intra-dialytic blood pressure
rather than a way to “ultrafiltrate” and
reduce circulating volume
Traditional “sodium modeling” results in a
gain of sodium, an increase in post-dialytic
thirst, resulting in increased interdialytic
wt gain
TEMPERATURE
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Normal dialysate temperature (37° C)
results in positive thermal gain,
resulting in vasodilation and drop in B/P
Lower temperature dialysate prevents
the thermal gain and results in greater
stability of B/P
Lowering dialysate temperature should
be one of the first considerations in
improving intra-dialytic stability
ANEMIA
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EPO
Iron Loss – at the LEAST – significant
iron losses 3x/wk (HD)
Iron absorption - impaired in ESRD due
to inflammation/hepcidin
Best mix of EPO + Iron is NOT KNOWN
In fact, despite processes that suggest
10-11 is the “appropriate” target, the
truth is that WE DON’T KNOW!
CALCIUM, PHOSPHOROUS, & PTH
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Contribute to Cardiovascular disease
The higher the phosphorous, the higher
the chances of the lining of blood
vessels turning into bone
The higher the Ca x Phos value, the
greater calcification of heart valves
Calcified heart valves are a potential
environment for endocarditis
Consider using a low Calcium dialysate
Original Article
Long Interdialytic Interval and Mortality among
Patients Receiving Hemodialysis
Robert N. Foley, M.B., David T. Gilbertson, Ph.D., Thomas Murray, M.S., and
Allan J. Collins, M.D
Patients receiving thrice-weekly hemodialysis have two 1-day intervals and
one 2-day interval between treatments.
This study shows that the risks of death and cardiovascular events leading to
hospital admission are increased during the long (2-day) interdialytic
interval.
N Engl J Med
Volume 365(12):1099-1107
September 22, 2011
Admission Rates and Mortality on Different
Days of the Week
Kaplan–Meier Curves for the Primary
End Point in the Two Study Groups.
Fellström BC et al. N Engl J Med 2009;360:1395-1407.