Transcript Kinetics of dialysis - Welcome to Zyrop Open Forum!

Dialysis Adequacy
Outline


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Historical background of hemodialysis duration
Measure of dialysis adequacy
Major problems with short (high speed) dialysis

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Increased mortality
Intradialytic hypotension
Poor blood pressure control
Poor blood access results
Need to change paradigm

Duration and frequency of dialysis should be
increased
In the beginning
In the 1960s, chronic HD sessions, as developed in
Seattle, Washington, were long procedures

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In-center: 20 – 40 hours/week on Kiil dialyzer. No blood pressure
meds needed in 22 of 24 patients
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8 – 10 hours thrice weekly at home. No blood pressure meds in
29 of 33 patients,
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Pendras JP, Erickson RV. Ann Intern Med. 1966; 64(2):293-311.
Eschbach JW Jr, Barnett BM, Cole JJ, Daly S, Scribner BH. Ann Intern Med 1967;
67(6):1149-1162.
No hypotensive episodes mentioned
Adequate dialysis in
the 1960’s
Pendras JP, Erickson RV. Hemodialysis: a successful therapy
for chronic uremia. Ann Intern Med. 1966; 64(2): 293-311.
Defined as the absence of clinical
symptoms and signs of uremia
Major symptoms and signs indicating inadequate
dialysis if no other etiology could be determined

Gastrointestinal and nutrition
 Nausea,
vomiting, anorexia, dysgeusia,
hypoalbuminemia

Neurological
 Motor
neuropathy, restless leg syndrome,
burning feet syndrome, insomnia,
depression, pruritus, decreased nerve
conduction velocity, sleep apnea
Twardowski Z. Acta Med Pol, 1974;
15: 227-243 and 245-254.
Major symptoms and signs indicating inadequate
dialysis if no other etiology could be determined

Cardiovascular
 hypertension, arrhythmia related to electrolyte
disturbances, pericarditis

Hemodialysis disequilibrium


headaches during or immediately after dialysis
Intradialytic and postdialytic hypovolemia

During dialysis: cramps, hypotension, backache, crash. After
dialysis: dizziness, hangover (thirst, headache, fatigue)
Twardowski Z. Acta Med Pol, 1974;
15: 227-243 and 245-254.
Why have clinical symptoms and signs
been rejected as an adequacy index?

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Symptoms and signs may have other etiology
Increased Kt/V does not influence the majority of these
symptoms
BUT
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Increasing time or duration of dialysis favorably
influences these symptoms
Instead of rejecting Kt/V as a measure of dialysis
adequacy, clinical symptoms and signs have been
rejected
In the 1970s, it was considered as obvious
that absence of uremic symptoms predicted
low mortality and hospitalizations
How is it now?
Adjusted relative risk
Relative Risk of Death and First Hospitalization by
Quintile Scores for Physical Component Summary
2,2
2,0
1,8
1,6
1,4
1,2
1,0
0,8
1.93
Death
Hospitalizations
1.52
1.36
1.56
1.46
1.17
1.33
1.14
<25
26-32
33-38
39-46
>46
Physical component summary score
Mapes D, et al. Health-related quality of life as a predictor of mortality
and hospitalizations: The DOPPS. Kidney Int. 2003; 64:339-349
Short hemodialysis is not a new fad

“Shortening the time of dialysis has always been
an aim of physicians”.

Rotellar E, et al: Why dialyze more than 6 hours a
week? ASAIO Trans1985; 31:538-545.
Early attempts to shorten dialysis
duration in the USA

12 – 16 hr/week with the use of coil dialyzers

Biochemical control similar to that reported by the
Seattle group

Schupak E, Merrill JP. Experience with long-term intermittent
hemodialysis. Ann Intern Med. 1965; 62(3):509-518.
Early attempts to shorten dialysis
duration in Europe
3 hours every other day or 4 hours thrice weekly for
an average of 11.2 hours per week
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Excellent biochemical control, hematocrits improved
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Cambi V, et al. Intensive utilisation of a dialysis unit. Proc Eur Dial
Transplant Assoc. 1973; 10:342-348.
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Cambi V, et al. Short dialysis schedules (SDS)- Finally ready to become a
routine? Proc Eur Dial Transplant Assoc. 1975; 11:112-120.
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No information on residual renal function.
Difficulties with blood pressure control

2 of 53 patients required bilateral nephrectomy
How could short hemodialysis be
justified and widely accepted?

Technical feasibility, economic incentives, and
medical/scientific justification


Barth RH. Short hemodialysis: big trouble in a small package.
In: Friedman EA. (ed.) Death on Hemodialysis: Preventable or
Inevitable. Dordrecht, The Netherlands, Kluwer Academic
Publishers, 1994; 143-157.
Technical feasibility and economic incentive had been
already shown by the Cambi group but some scientific
support and some mathematical formula were needed
to define an adequate dose of dialysis and justify short
treatment duration
Medical/scientific justification of
short hemodialysis

Godsend for short HD

Kt/Vurea
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Urea clearance times time divided by urea
distribution volume
National Cooperative Dialysis Study
(NCDS) accepted Kt/Vurea as a single
measure of dialysis adequacy
Conclusion of NCDS
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Time of dialysis has little influence on results
provided that dialyzer clearance is high
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Harter HR. Review of significant findings from the National
Cooperative Dialysis Study and recommendations. Kidney Int
Suppl. 1983; 13:S107-12.
Kt/Vurea should be over 0.95/treatment with
three times weekly dialysis

Gotch FA, Sargent JA. A mechanistic analysis of the National
Cooperative Dialysis Study (NCDS). Kidney Int 1985;
28:526-534.
Shortcomings of NCDS
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The study was conducted for only 52 weeks in the early
1980’s
Clinical assessment rejected as a measure of dialysis
quality; hospitalizations accepted instead
Residual renal function was not taken into account
in spite that many patients were of short vintage and must
have had substantial urine output
Time of dialysis rejected as a measure of dialysis
adequacy based on p = 0.06

Forgotten truth: Absence of evidence is not evidence of
absence
Consequences of Kt/Vurea concept

Time of dialysis may be shortened if
dialysis clearance is proportionately
increased
Efficient dialyzers
 High blood flow
 High dialysate flow

Attempts of ultra-short dialysis
Hemodiafiltration, 115 min three times weekly

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Two-hr, 3weekly, 500 ml/min BF, 5 m2 dialyzer
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von Albertini B, et al. High-flux hemodiafiltration: under six
hours/week treatment. ASAIO Trans 1984; 30:227-231.
Rotellar E, et al: Why dialyze more than 6 hours a week?
ASAIO Trans1985; 31:538-545.
An editorial posed a question in the title “Are there
limitations to shortening dialysis treatment?” and did not
answer affirmatively

Collins AJ, Keshaviah PR. ASAIO Trans. 1988; 34(1): 1-5.
Dialysis duration in the last quarter of
the 20th century

“In contrast to AIDS, the virus of short
duration dialysis has crossed the ocean
from the old world and has invaded the
USA”

Wizemann V, Kramer W. Short-term dialysis Long-term complications. Ten years
experience with short-duration renal
replacement therapy. Blood Purif. 1987;
5(4):193-201.
Dialysis duration in the last quarter of
the 20th century

Even though European dialysis facilities
were first to introduce short dialysis, most
centers practiced longer dialysis sessions
that those in the USA. Japanese centers
practiced the longest dialysis sessions.

Goodkin DA, Young EW. DOPPS update.
Contemporary Dialysis & Nephrology. 2001;
October, pp 36 – 40.
Are any data that dialysis duration
influences mortality?

In the period 1982-1987, hemodialysis mortality in
the United States was found to be 22% higher than
in Europe and 40% higher than in Japan, where
dialysis durations were longer

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Held PJ, et al. Am J Kidney Dis 1990 May;15(5):451-7.
Time of dialysis below 5 hrs an important predictor of
death according to Japanese Dialysis Registry

Shinzato T, et al. Nephrol Dial Transplant 1997; 12 (5): 884-888.
Mortality in short dialysis in
Germany

“The proportion of deaths in the Federal
Republic of Germany was twice as high in
short dialysis”
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Kramer P, et al. Combined report on regular
dialysis and transplantation in Europe, XII, 1981.
Proc Eur Dial Transplant Assoc. 1983;19: 4-59.
Mortality and dialysis duration in the
USA in the late 1980s

Relative mortality risk was about 20% higher in
patients receiving dialysis duration <3.5 hrs
compared to those with treatment >3.5 hrs.
Most shorter treatments were received by
patients in for-profit units. This indicates that the
major incentive for short dialysis was financial.
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Held PJ, Levin NW, Bovbjerg RR, Pauly MV, Diamond LH. Mortality and
duration of hemodialysis treatment. JAMA. 1991; 265(7): 871-875.
Berger EE, Lowrie EG. Mortality and the length of dialysis. JAMA. 1991;
265(7):909-910.
Duration of dialysis and
mortality in Japan

Analysis of the results in 71,193 patients of
Japanese HD Registry showed statistically
significant, gradual decrease of mortality with
increased dialysis time from 3.5 to 5.5 hours.
Further decrease in mortality with dialysis
duration >6 hours, but statistically insignificant
because of small number of patients in this time
range
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Shinzato T, Nakai S. Do shorter hemodialyses
increase the risk of death? In J. Artif Organs. 1999;
22(4):199-201
Blood pressure control in the first
report on shorter dialysis in the USA

In a group of 22 patients, 8 required
antihypertensive therapy, 4 required bilateral
nephrectomy, and two died of cerebral
hemorrhage

Schupak E, Merrill JP. Experience with long-term
intermittent hemodialysis. Ann Intern Med. 1965;
62(3):509-518
Sodium retention and hypertension
in short dialysis
Exchangeable sodium increases with 14.8 hr/wk
compared to 18 hr/wk dialysis, and more patients
require antihypertensive drugs.
“Problems of hypertension and the side effects of its
treatment, both medical and surgical, should be
weighed against the social and economic advantages
of short dialysis in deciding on the ideal schedule.”
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Sellars L, Robson V, Wilkinson R. Sodium retention and
hypertension with short dialysis. Br Med J. 1979; 1(6162):
520-521.
Intradialytic hypotension (IDH) and
duration of dialysis
Intradialytic hypotension (IDH) occurs in 25 to 50% of
short, thrice weekly hemodialysis treatments in the
United States.
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Schreiber MJ Jr. Am J Kidney Dis. 2001; 38(Suppl 4):S1-10.
Dialysis hypotension occurs because a large volume of
blood water and solutes are removed over a short
period, exceeding the plasma refilling rate and reduction
of venous capacity
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Daugirdas JT. Am J Kidney Dis 2001; 38(4 Suppl 4): S11-17.
Sherman RA. Am J Kidney Dis. 2001; 38(4 Suppl 4): S18-25.
DBV (%)
Lopot et al. Hemodial Int 2000; 4:8-14
Recommended maneuvers to
decrease IDH episodes
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Higher dialysate sodium, calcium, and potassium
Isolated ultrafiltration followed by dialysis
Lower dialysate magnesium, high dialysate potassium
Lower dialysate temperature
Bicarbonate instead of acetate dialysate
Predialysis withdrawal of blood pressure medications
Blood pressure raising drugs, such as ephedrine,
fludrocortisone, caffeine, and midodrine
Sodium and ultrafiltration modeling (profiling)
Stiller S,. A critical review of sodium profiling for hemodialysis. Semin Dial. 2001;14(5): 337-347.
DBV (%)
Change in BV response with Na profile
Lopot et al. Hemodial Int 2000; 4:8-14
Does sodium profiling work?
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In most short studies IDH rates decreased
Long term studies unavailable
Sodium profiling works if sodium balance is
positive

Iselin H, Tsinalis D, Brunner FP. Sodium balanceneutral sodium profiling does not improve dialysis
tolerance. Swiss Med Wkly. 2001;131(43-44): 635639.
Consequences of positive sodium
balance
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Chronic fluid volume overload until new equilibrium
is achieved
Decreases IDH rates
Causes volume dependent hypertension
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>80% of patients in the USA are on antihypertensive
drugs
LVH
Increased cardiovascular mortality
Comorbidities (%) in Euro- DOPPS, Japan,
and the USA
Euro-DOPPS
Japan
USA
Coronary artery disease
28.7
18.7
48.3
Congestive heart failure
24.1
5.6
43.9
Other cardiac problem
36.2
23.9
34.6
Hypertension
72.5
56.1
83.7
Peripheral vascular disease
22.0
10.9
24.3
Cerebrovascular disease
13.2
11.8
16.8
Dyspnea
18.9
2.4
27.5
Fukuhara S, et al. Health related quality of life among dialysis patients
on three continents: The DOPPS. Kidney Int. 2003; 64:1903-1910
Prevention of IDH


The simplest and almost always effective is prolongation
of dialysis to match ultrafiltration rate with plasma
refilling rate
Although obviously logical, this maneuver is not
recommended by DOQI guidelines and most review
papers on the subject

Short dialysis time seems to be a
sacrosanct element of dialysis prescription
Fewer IDH episodes and better BP
control with longer dialysis
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Fishbane SA, Scribner BH. Blood pressure control in dialysis patients.
Semin Dial. 2002; 15(3):144-145.
Hörl MP, Hörl WH. Hemodialysis-associated hypertension:
pathophysiology and therapy. Am J Kidney Dis 2002; 39(2):227-244.
Locatelli F, Manzoni C. Duration of dialysis session – Was Hegel right?
Nephrol Dial Transplant. 1999; 14(3):560-563.
Covic A, et al. Long-hours home haemodialysis - the best renal
replacement therapy method? QJM 1999; 92(5):251-260.
McGregor DO, et al. A comparative study of blood pressure control with
short in-center versus long home hemodialysis. Blood Purif 2001;
19(3):293-300.
Katzarski KS, et al. Extracellular volume changes and blood pressure
levels in hemodialysis patients. Hemodial Int. 2003; 7(2): in press.
Advantages of short dialysis
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For the provider
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Financial
More shifts
 No benefit for home hemodialysis
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For patients
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Shorter time while tethered to dialyzer
Shorter time while sitting in chair (in the USA)
Patients’ position during dialysis

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Most Japanese and many European patients are
dialyzed in beds in the supine position
Most US patients are dialyzed while sitting in chairs

In the early days of hemodialysis in the USA it was
assumed that patients would feel better psychologically if
they came to the dialysis unit but were not treated like
patients, dressed in hospital garbs and lying in beds, but
rather like visitors sitting in chairs and casually dressed.
A HD patient in the USA
A patient of Dr. Charra
in Tassin, France
Why patients request short dialysis
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Patients are told that longer dialysis is not better
than short dialysis
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No benefit - more time wasted
Sitting in a chair for a long time is uncomfortable

In the sitting position, there is translocation of body
fluids to the lower extremities; consequently,
hypotensive episodes are more likely, especially during
the second half of HD
Why patients request short dialysis

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Patients want to have taken away this “miserable
last hour of dialysis”
It is impossible to take away the last hour of
dialysis but patients’ pressure is frequently
successful, HD is shortened and target weight
increased
 Interdialytic
blood pressure increases with
all its consequences
Prescribed blood flow, HD duration, and percent fistula in
prevalent patients in Japan, Euro-DOPPS, and the USA
400
350
300
250
200
400
Calculated from DOPPS data kindly
provided by Dr. Phil Held
300
240
228
210
200
150
100
50
0
90,2
73,7
19,9
Japan
Blood flow (mL/min)
Euro-DOPPS
HD Duration (min)
USA
Fistula (%)
A-V fistula survival is
markedly higher in Europe
compared to the USA
Pisoni RL, Young EW, Dykstra DM, Greenwood RN,
Hecking E, Gillespie B, Wolfe RA, Goodkin DA,
Held PJ. Vascular access use in Europe and the
United States: Results from the DOPPS. Kidney
Int. 2002; 61(1):305-316.
High blood flow rates and A-V
fistula problems

Primary A-V wrist fistula providing <300
mL/min blood flow is sufficient for long
dialysis but is in jeopardy if short dialysis
is practiced

May be deemed unusable and other access
created
 Allon
M, Robbin ML. Increasing arteriovenous
fistulas in hemodialysis patients: Problems and
solutions. Kidney Int. 2002; 62(4):1109-1124.
High blood flow rates and A-V
fistula problems
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A-V fistula may be damaged by repeated
attempts to achieve higher blood flows, using
tourniquets and other maneuvers
Hypotensive episodes rapidly reduce fistula
blood flow, predispose to damage of the intima
by suction of the inflow needle with consequent
clotting
High blood flow and catheter
problems
High blood flow requires a large internal
diameter of the catheter
Large diameter catheter fits the vein too
tightly and predisposes to damage of the
vein wall, vein thrombosis and stenosis

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
Davenport A. Central venous catheters for hemodialysis: How
to overcome the problems. Hemodial Int. 2000; 4:78-82.
The results of the HEMO study
Eknoyan et al. NEJM. 2002; 347(25):2010-2019.

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No major benefit of spKt/Vurea above 1.3 in
thrice-weekly dialysis, except in woman
Higher Kt/Vurea was achieved mainly by
increasing K

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The average blood flow was 311 mL/min in the low
dose group and 375 mL/min in the high dose group.
The average dialysis duration was 190 min in the low
dose group and 219 min in the high dose group
Importance of dialysis frequency
higher than thrice weekly

Sudden and cardiac death highest on Monday and Tuesday
in HD but not in CAPD


Bleyer AJ; Russell GB; Satko SG. Kidney Int 1999; 55:1553
QOD, 4, 5, 6, and 7 times weekly HD decrease fluctuations
in pre and post dialysis fluid volumes and solute
concentrations

Decrease interdialytic and intradialytic symptoms

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IDH, cramps, and postdialysis hangover
Improve mental health, energy, social functioning, physical activity,
vitality, blood pressure control with decreased use of
antihypertensive drugs, and hematocrit with decreased use of
erythropoietin
Reasons that patients do better on quotidian HD with
the same overall weekly dialysis duration

Alleviation of hemodialysis “unphysiology”


Kjellstrand CM, et al. The "unphysiology" of dialysis: A major cause of
dialysis side effects? Kidney Int 1975; 7: S30-S34.
Less swings in concentrations of all solutes (lower
time average deviation)


Maintenance of concentrations within normal limits


Urea, creatinine, uric acid, etc.
Potassium, phosphorus, calcium, pH, bicarbonate
Less swings in hydration/ECV


Lower interdialytic weight gains
Elimination of hypervolemia/hypovolemia
Concentration
Weekly
substance
concentrations
in routine HD
Weekly
fluctuations
in routine hemodialysis
NO NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
Time
Concentration
Weekly
fluctuations
in daily hemodialysis
Weekly
substance
concentrations
in daily HD
NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
Time
Call for change of paradigm




Kt/V should be abandoned as the most
important measure of dialysis quality
Clinical symptoms and signs should be
accepted instead
Blood flow should range from 200 to 300 ml/min
High performance dialyzers should continue to
be used
Call for change of paradigm




Time and frequency of dialysis must be adjusted to residual
urine output and tolerance of ultrafiltration. Ultrafiltration
rate should range from 0.5%-1.5% of body weight/hr
Dialysis frequency and duration should permit the
achievement of blood pressure control without
antihypertensive medications in 90%-95% of patients
Anuric patients should not have dialysis shorter than five
hours in thrice weekly schedule.
More frequent dialysis is preferred in anuric patients, but
weekly dialysis time should not drop below 15 hrs
Festina lente
[hasten slowly (deliberately)]
Motto of Gaius Julius Caesar
Octavian Augustus (63BC - 14AD)
The first and greatest Emperor (27BC - 14AD)
This Latin motto should be
written on a wall of every
hemodialysis room