Fallacies of Short, ThriceWeekly Hemodialysis

1
Fallacies of Short, Thrice-Weekly Hemodialysis

• Zbylut J. Twardowski, MD, PhD
• University of Missouri

Short, thrice weekly HD is inadequate regardless
of Kt/V
2
Outline

• Historical background of hemodialysis duration
• Measure of dialysis adequacy
• Major problems with short (high speed) dialysis
• Increased mortality
• Intradialytic hypotension
• Poor blood pressure control
• Poor blood access results
• Need to change paradigm
• Duration and frequency of dialysis should be
  increased

3
In the beginning

• In the 1960s, chronic HD sessions, as developed
  in Seattle, Washington, were long procedures
• In-center 20 40 hours/week on Kiil dialyzer.
  No blood pressure meds needed in 22 of 24
  patients
• Pendras JP, Erickson RV. Ann Intern Med. 1966
  64(2)293-311.
• 8 10 hours thrice weekly at home. No blood
  pressure meds in 29 of 33 patients,
• Eschbach JW Jr, Barnett BM, Cole JJ, Daly S,
  Scribner BH. Ann Intern Med 1967
  67(6)1149-1162.
• No hypotensive episodes mentioned

4
Adequate dialysis in the 1960sPendras 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  

5
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

6
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)

7
Why have clinical symptoms and signs been
rejected as an adequacy index?

• Symptoms and signs may have other etiology
• Increased Kt/V does not influence the majority of
  these symptoms
• BUT
• 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

8
In the 1970s, it was considered as obvious that
absence of uremic symptoms predicted low
mortality and hospitalizations

• How is it now?

9
Relative Risk of Death and First Hospitalization
by Quintile Scores for Physical Component Summary
1.93
1.52
1.36
1.56
1.46
1.17
1.33
1.14
Mapes D, et al. Health-related quality of life as
a predictor of mortality and hospitalizations
The DOPPS. Kidney Int. 2003 64339-349
10
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 31538-545.

11
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.

12
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
• Excellent biochemical control, hematocrits
  improved
• Cambi V, et al. Intensive utilisation of a
  dialysis unit. Proc Eur Dial Transplant Assoc.
  1973 10342-348.
• Cambi V, et al. Short dialysis schedules (SDS)-
  Finally ready to become a routine? Proc Eur Dial
  Transplant Assoc. 1975 11112-120.
• No information on residual renal function.
• Difficulties with blood pressure control
• 2 of 53 patients required bilateral nephrectomy

13
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

14
Medical/scientific justification of short
hemodialysis

• Godsend for short HD
• Kt/Vurea
• Urea clearance times time divided by urea
  distribution volume
• National Cooperative Dialysis Study (NCDS)
  accepted Kt/Vurea as a single measure of dialysis
  adequacy

15
Conclusion of NCDS

• Time of dialysis has little influence on results
  provided that dialyzer clearance is high
• Harter HR. Review of significant findings from
  the National Cooperative Dialysis Study and
  recommendations. Kidney Int Suppl. 1983
  13S107-12.
• 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 28526-534.

16
Shortcomings of NCDS

• The study was conducted for only 52 weeks in the
  early 1980s
• 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

17
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

18
Attempts of ultra-short dialysis

• Hemodiafiltration, 115 min three times weekly
• von Albertini B, et al. High-flux
  hemodiafiltration under six hours/week
  treatment. ASAIO Trans 1984 30227-231.
• Two-hr, 3?weekly, 500 ml/min BF, 5 m2 dialyzer
• Rotellar E, et al Why dialyze more than 6 hours
  a week? ASAIO Trans1985 31538-545.
• 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.

19
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.

20
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.

21
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
• Held PJ, et al. Am J Kidney Dis 1990
  May15(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.

22
Mortality in short dialysis in Germany

• The proportion of deaths in the Federal Republic
  of Germany was twice as high in short dialysis
• Kramer P, et al. Combined report on regular
  dialysis and transplantation in Europe, XII,
  1981. Proc Eur Dial Transplant Assoc. 198319
  4-59.

23
Mortality and dialysis duration in the USA in the
late 1980s

• Relative mortality risk was about 20 higher in
  patients receiving dialysis duration 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.
• 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.

24
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
• Shinzato T, Nakai S. Do shorter hemodialyses
  increase the risk of death? In J. Artif Organs.
  1999 22(4)199-201

25
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

26
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.
• Sellars L, Robson V, Wilkinson R. Sodium
  retention and hypertension with short dialysis.
  Br Med J. 1979 1(6162) 520-521.

27
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.
• 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
• 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.

28
Lopot et al. Hemodial Int 2000 48-14
DBV ()
29
Recommended maneuvers to decrease IDH episodes

• 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)

30
Stiller S,. A critical review of sodium profiling
for hemodialysis. Semin Dial. 200114(5) 337-347.
31
Change in BV response with Na profile
DBV ()
Lopot et al. Hemodial Int 2000 48-14
32
Does sodium profiling work?

• 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
  balance-neutral sodium profiling does not improve
  dialysis tolerance. Swiss Med Wkly.
  2001131(43-44) 635-639.

33
Consequences of positive sodium balance

• Chronic fluid volume overload until new
  equilibrium is achieved
• Decreases IDH rates
• Causes volume dependent hypertension
• 80 of patients in the USA are on
  antihypertensive drugs
• LVH
• Increased cardiovascular mortality

34
Comorbidities () in Euro- DOPPS, Japan, and the
USA
Fukuhara S, et al. Health related quality of life
among dialysis patients on three continents The
DOPPS. Kidney Int. 2003 641903-1910
35
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

36
Fewer IDH episodes and better BP control with
longer dialysis

• 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.

37
Advantages of short dialysis

• For the provider
• Financial
• More shifts
• No benefit for home hemodialysis
• For patients
• Shorter time while tethered to dialyzer
• Shorter time while sitting in chair (in the USA)

38
Patients position during dialysis

• 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.

39
A HD patient in the USA
40
A patient of Dr. Charra in Tassin, France
41
Why patients request short dialysis

• Patients are told that longer dialysis is not
  better than short dialysis
• 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

42
Why patients request short dialysis

• 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

43
Prescribed blood flow, HD duration, and percent
fistula in prevalent patients in Japan,
Euro-DOPPS, and the USA
Calculated from DOPPS data kindly provided by
Dr. Phil Held
44
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.

45
High blood flow rates and A-V fistula problems

• Primary A-V wrist fistula providing 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.

46
High blood flow rates and A-V fistula problems

• 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

47
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
• Davenport A. Central venous catheters for
  hemodialysis How to overcome the problems.
  Hemodial Int. 2000 478-82.

48
The results of the HEMO studyEknoyan et al.
NEJM. 2002 347(25)2010-2019.

• 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
• 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

49
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
  551553
• 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
• 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

50
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)
• Urea, creatinine, uric acid, etc.
• Maintenance of concentrations within normal
  limits
• Potassium, phosphorus, calcium, pH, bicarbonate
• Less swings in hydration/ECV
• Lower interdialytic weight gains
• Elimination of hypervolemia/hypovolemia

51
Weekly fluctuations in routine hemodialysis
NO NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
52
Weekly fluctuations in daily hemodialysis
NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
53
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

54
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

55
Festina lente hasten slowly (deliberately)Mott
o 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