September 19, 2004 NKF, Chicago, Illinois
Fallacies of Short, Thrice-Weekly Hemodialysis
Zbylut J. Twardowski, MD, PhD
University of Missouri
Short, thrice weekly HD is inadequate regardless of Kt/V
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
Outline
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
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
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
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.
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)
Major symptoms and signs indicating inadequate dialysis if no other etiology could be determined
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
In the 1970s, it was considered as obvious that absence of uremic symptoms predicted
low mortality and hospitalizations
How is it now?
Relative Risk of Death and First Hospitalization by Quintile Scores for Physical Component Summary
0,81,01,21,41,61,82,02,2
<25 26-32 33-38 39-46 >46
Physical component summary score
Adjusted relative risk
Death Hospitalizations
1.56 1.46
1.33
1.17
1.93
1.521.36
1.14
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
Excellent biochemical control, hematocrits improved Cambi V, et al. Intensive utilisation of a dialysis unit. Proc Eur Dial
Transplant Assoc. 1973; 10:342-348. Cambi V, et al. Short dialysis schedules (SDS)- Finally ready to become a
routine? Proc Eur Dial Transplant Assoc. 1975; 11:112-120.
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
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
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; 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
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 von Albertini B, et al. High-flux hemodiafiltration: under six
hours/week treatment. ASAIO Trans 1984; 30:227-231. Two-hr, 3weekly, 500 ml/min BF, 5 m2 dialyzer
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 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” 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. 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 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.”
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.
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.
BV
(%
)
Lopot et al. Hemodial Int 2000; 4:8-14
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)
Stiller S,. A critical review of sodium profiling for hemodialysis. Semin Dial. 2001;14(5): 337-347.
BV
(%
)
Lopot et al. Hemodial Int 2000; 4:8-14
Change in BV response with Na profile
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. 2001;131(43-44): 635-639.
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
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
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.
Fewer IDH episodes and better BP control with longer dialysis
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)
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.
A HD patient in the USA
A patient of Dr. Charra in Tassin, France
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
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
200
240
90,2
300
228
73,7
400
210
19,90
50
100
150
200
250
300
350
400
Japan Euro-DOPPS USA
Blood flow (mL/min) HD Duration (min) Fistula (%)
Calculated from DOPPS data kindly provided by Dr. Phil Held
Prescribed blood flow, HD duration, and percent fistula in prevalent patients in Japan, Euro-DOPPS, and the USA
A-V fistula survival is markedly higher in Europe
compared to the USAPisoni 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
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
Davenport A. Central venous catheters for hemodialysis: How to overcome the problems. Hemodial Int. 2000; 4:78-82.
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
The results of the HEMO studyEknoyan et al. NEJM. 2002; 347(25):2010-2019.
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
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)
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
Weekly substance concentrations in routine HD
Time
Concentration
NO NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
Weekly fluctuations in routine hemodialysis
Weekly substance concentrations in daily HD
Time
Concentration
NORMAL RANGE OF ECV, K, Bicarb, P, Ca, pH
Weekly fluctuations in daily hemodialysis
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
