Dr hesham elsayed hd adequacy and dose optimization

1. Hemodialysis
Adequacy And Dose
Optimization
HESHAM ELSAYED
PROFESSOR OF NEPHROLOGY
AIN SHAMS UNIVERSITY

2. HD DOSE PRESCRIPTION :AN ADEQUACY PUZZLE OR a CONFLICTING TERMS ?
FLUX
TIME
Frequancy
Duration
UFR
MARKER?
KT
Over what
ALL ARE IN ONE
BASKET
NO ONE SIZE FIT FOR
ALL PATIENTS

3. Clin J Am Soc Nephrol 12: 839–847, 2017

5. HD : a Filtration Therapy points of improvement
Enhance
the
Clearance
HD
Removal
by
Filtration
Removal
by
Adsorption
Flux HDF
17 %
Solute
permeability
Solute
Dragging

6. Towards Better Dialysis current achievements
Membranes
Higher SC
Removing MM
Higher Convection
TTT
Amplified Clearance
HE-HDF
Extended and
Frequent Sessions
Improve compartmental
Removal
More Physiological
Expanded HD
HDx
Removal of bigger molecule
Than HFD
Adsorption
Remove Bigger molecules
Protein Bound Toxins
Line of improvements

7. Therapeutic Approach Kidney International (2014)

8. Haemodialysis Therapy: A Never-Ending Journey
•LF Dialysis = Small solute KT/V Sunset of KT/V
• High Flux Dialysis and HDF ?? HD dose prescription
• Medium Cut off Dialysis ?? HD dose prescription
• High Cut off Dialysis ?? HD dose prescription

9. "Optimal" Dialysis Dose prescription Should
Goal
Comfortable HD
Better Control of BP ,
Anemia , CKD-MBD
Better control of Uremic Toxins
and Volume state
Better
Survival
And HRQOL
High
Permeable
membranes
Prolonged Time
More
Frequent

10. KT/V urea is still the official marker of Adequacy !!!!!!
More
Frequent
HD
For thrice-weekly HD in
patients with low residual
native kidney clearance
(Kru < 2 mL/min), the
target spKt/V dose
remains 1.4 volumes per
dialysis, minimum dose
1.2.

11. Men and Women are equal on St Kt/V Women need More HD Dose with BSA correction

12. HD DOSE PRESCRIPTION AN ADEQUACY PUZZLE OR a CONFLICTING TERMS
FLUX
TIME
FREQ
UFR
MARKER?
KT/V

13. FLUX AND SOLUTE PERMEABILITY
cut off = SC 0.1
LF MF HF
Super
Flux
MCO HCO
Plasma
Filter
5000 8000 20000 3000 45000 65000
Plasma
Filter
Cut off

14. Targeting Beyond B2m in MW

15. Medium cut-off membranes - closer to the natural
kidney removal function ( MCO )

16. The SC of the HD membrane determine the
solute Removal type ( size in KD )
while the UFR determine the Magnitude of Removal

17. Medium cut off Membrane MCO
Bigger pore
Radius
M
M
Albumin
BM

18. MCO
Higher Membrane
Permeability up to 45 kd
HDF
Membrane Permeability
+
TMP dragging
Quantification is
needed
Quantification is
calculated
More RCT is needed RCT on longterm
benefits

19. HD : convection volume versus high permeability
Removal of
MM
HDF
Depends on
Ultrafiltration rates and
TMP in a specified
volume
MCO
Depends on Membrane
Permeability

20. `High Permeability
with Obligatory water loss + Backfiltration
Maximum UF
Higher pressure
Lower UF
Lower pressure

21. HD Backfiltration internal HDF
Pressure Drop
Back filtration volume is risky for
Pyrogen transfer `… volume ??

22. HDF Dose
Depends on :
 1-Blood volume
processed.
 2- UF and substitution
volume
Volume of
processed Blood
Volume of
convection
volume
Filtration Fraction in
the Safe Limits
between 25 – 30 %
FF = UFR / QB

23. B2m RR% is a linear with substitution volume
45%
50%
58%
65%
70%
78%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
0 40 60 80 100 120
ml/min

24. MCO MEMBRANE
Expanded HD ( Expanded than HF removal )
ERA-EDTA 2017 MADRID
MCO membranes show permeability close to that of the natural
kidney.
Their MWCO values indicate that, when used in hemodialysis
treatments, they allow for removal of an expanded range of uremic
toxins compared to
conventional high-flux membranes.

25. Potential Benefits of MCO membranes
Expanded
HD
Greater clearance of
λFLC (45 kDa in size
limited effect on
protein-bound toxins
downregulate the expression
of both IL-6 and tumor
necrosis factor-α mRNA
removal of soluble
mediators is
enhanced
Transcription of pro-
inflammatory cytokines
in peripheral leukocytes
is markedly reduced
Higher Albumin loss
2.9 – 7 gm
Albumin Loss in
conventional HF
is below 0.4 gm

26. Performance of hemodialysis
depends of membrane and
technique
Nephrol Dial Transplant (2017)
32 (1): 165-172

27. Performance of
hemodialysis
depends of
membrane and
technique
Nephrol Dial
Transplant (2017)
32 (1): 165-172

28. HDX versus HD RR % ERA-EDTA 2017 MADRID
Adequacy update :Targeting Beyond B2m in MW

29. Limitations for MCO dialysis
THE CALCULATION BASED ON THE MARKETING MESSAGE
Solute removal by convection = UFR X SC OF THE
SOLUTE
HDFbased
FLUX
Based

30. HDF prescription
Solute removal by convection = UFR X SC OF THE
SOLUTE
Bigger solute remove by High TMP = solute
Dragging

31. HDF requirements
AINS SHAMS UNIVERSITY TREND
Substitution volume > 23 l /
session
Monitoring for TMP
QB > 350 ml/min
Dialyzer SC for B2m > 0.8
Dialyzer SC for Myoglobin > 0.4

32. HDF requirements
AINS SHAMS UNIVERSITY
TREND
1- HD machines with
Feedback control
2-HF dialyzer 2.0-2.2m2
3- well educated personnel
4- water treatment control
Monitor
SV
TMP
Dialyzer
2.0 – 2.2
m2

33. Ain Shams university Hospital
HDF sessions 200 Sessions FF % achieved
27.9
30.85
26
26.5
27
27.5
28
28.5
29
29.5
30
30.5
31
31.5
FF%
FF %
UFR/QB Polyflux 1.7 m2 HF
Platinum 2.2 m2 HF
2.9
2.01 2.33
3.18
21.66 21.8 21.95
21
10.03 10.03 10.11 10.43
0
5
10
15
20
25
Group monitors Group monitors Group monitors Group monitors
UF and substitution volumes Liters And Patients
Hemoglobin UF Subst volume HB

34. 2293 patients with a minimum of 2 years of follow-up were analysed

35. 6 L 10 L 14 l 18 L 21 L 25 L 28 L 30 L
survival
Convective Dose of dialysis ( liters of post HDF )
LOW HDF
HE OL- HDF

36. Kidney Int. 2015 Nov;
Parameter Value
Treatment time per session (min;
mean±s.d.)
241.5±14.0
Patients on thrice weekly treatments (%) 96
Effective blood flow (ml/min; mean±s.d.) 404.9±69.4
Dialyzer surface (m2; mean±s.d.) 1.54±0.20
Post-dilution HDF (%) 100%
Effective dialysate flow (ml/min;
mean±s.d.)
506.1±53.6
Substitution flow (ml/min; mean±s.d.) 91.4±13.6
Substitution flow normalized to BSA
(ml/min/m2, mean±s.d.)
52.2±11.4

37. analysis of relative survival rate (with 95% confidence interval) versus convection volume in (a)
l/week and (b) l/week/m2 body surface area.

38. pre-dialysis ß2-M concentration (with 95% confidence interval) versus convection
volume. (a) l/week. (b) l/week/m2 body surface area.

39. Albumin Leakage during HD :
is it worth or Beneficial ?
Implications of Albumin Leakage for Survival in
Maintenance Hemodialysis Patients: A 7-year
Observational Study 740 patients follow up
Data is toward accepted 3 gm loss / session
More RCTS is still needed
27 April 2017

40. Dose of removal depends on HD Membrane
international journal of artificial organVol. 40 Issue 7 | Jul 2017 | pp. 313 - 366
Dialyzer type Water
permeability
(mL/(m2*h*mmH
g))
Sieving coefficient
ß2-
Microglobulin
Albumin Loss
Grams
Low-flux 10-20 - zero
High-flux 200-400 0.7-0.8 0.2 0.4 HD
1-4 HDF
Medium cut-off 600-850 1.0 3-7
High cut-off 1100 1.0 > 7 HD

41. Albumin Loss during HD
1
3
5
0
1
2
3
4
5
6
Albumin loss / session
Albumin Loss / session in gm HD
Minimal Moderate Marked

42. Albumin leakage in online HDF, more convective
transport, more losses (TMP)
79
403
869
1840
0
200
400
600
800
1000
1200
1400
1600
1800
2000
Albumin Loss 20 L Albumin Loss 30 L
Albumin Loss in dialysate mg
FX 1000 Polyflux 21 H
Ther Apher Dial. 2015 Jun

43. HD dose
prescription
Volume state
and UFR

44. Fluid Overload “FO”
 severe FO, defined as an expansion of the extracellular fluid
by more than 15% (around 2.5 L in a person weighing 70 kg).
 Fluid overload ( FO ) and Fluid Depletion ( FD ) Both has a
higher risk for mortality ( U shaped )
Data analysis for 8883 patients for 12 months follow up
Kidney International (2017) 91

45. “FO” and “FD” survival Kidney International (2017) 91
Normovolemia
Moderate volemia + > 1.1
Volume depletion - > 1.1 L
severe hypervolemia + > 2.5 L
Extreme hypervolemia + > 5 L

46. UFR and mortality
Retrospective cohort 118,394 hemodialysis patients dialyzing in a large
dialysis organization, 2008 to 2012 (December 2016Volume 68, Issue 6 )
1.22
1.31
0.8
0.9
1
1.1
1.2
1.3
1.4
adjusted HR
< 10 ml/kg/h > 10 ml/kg/h > 13 ml/kg/h

47. HD DOSE PRESCRIPTION AN ADEQUACY PUZZLE OR a CONFLICTING TERMS
FLUX
TIME
FREQ
UFR
MARKER?
KT/V

48. Haemodialysis Prescription for Incident Patients:
Twice Seems Nice, But Is It Incremental?
American Journal of Kidney Diseases 2016
WE ALL DO INCRIMENTAL HD BEFORE THE TERMINOLOGY IS BORN

49. Hemodialysis Prescription for Incident Patients:
Twice Seems Nice, But Is It Incremental?
American Journal of Kidney Diseases 2016 68,
 The optimal regimen for patients initiating hemodialysis
therapy is not known.
 It is plausible that the routine practice of fixed-dose thrice-
weekly hemodialysis in incident patients with substantial RKF
may be harmful, contributing to accelerated loss of this residual
function

50. Nephrol Dial Transplant (2015) 30 (10):
Evaluate
Monthly
Augmented HD
Frequency
Duration
Flux
HDF
3 Phases Approach for
HD Dose presription

51. Incremental
hemodialysis
prescription with
adjustment of
hemodialysis dose
based on Residual
kidney function
Nephrol Dial Transplant (2015) 30 (10):

52. (10)CRITERIA FOR IMPLEMENTING INCRIMENTAL HD
Am J Kidney Dis. 2014 Aug; 64(2): 181–186.
 Good RKF with a urine output >0.5 L/day
 Limited fluid retention between 2
consecutive HD treatments with a fluid
gain <2.5 kg (or less than 5% of the ideal
dry weight) without HD for 3 to 4 days
 Limited or readily manageable
cardiovascular or pulmonary symptoms
without clinically significant fluid
overload**
 Suitable body size relative to RKF; patients
with larger body size may be suitable for
2x/wk HD if not hypercatabolic
 Hyperkalaemia (K, >5.5 mEq/L) is
infrequent or readily manageable
 Hyperphosphatemia (P, >5.5 mg/dL) is
infrequent or readily manageable
 Good nutritional status without florid
hypercatabolic state
 Lack of profound anemia (Hb >8 g/dL) and
appropriate responsiveness to anemia
therapy
 Infrequent hospitalization and easily
manageable comorbid conditions
 Satisfactory HRQOL

53. CRITERIA FOR IMPLEMENTING INCRIMENTAL
HD
Am J Kidney Dis. 2014 Aug; 64(2): 181–186.
Implementation Strategies
In order to initiate and maintain 2x/wk HD, the patient should
meet the first criterion (urine output >0.5 Lit/day) plus most (5 out
of 9) of the other criteria.
Examine these criteria every month in all 2x/wk HD patients and
compare outcome between 2x/wk and 3x/wk HD to assure
outcome non-inferiority for continuation of 2x/wk HD

54. The finding of two frequency peaks of
sudden death, immediately before and after
the first weekly haemodialysis session,
suggests that daily haemodialysis, or at
least the abolition of the long interdialytic
interval during the weekend, could be
helpful in reducing this kind of mortality.
Frequency

55. BFL ( QB )

56. Effect of Blood Flow Rate on Adequacy
360
420
330
340
350
360
370
380
390
400
410
420
430
Blood Flow ml/min
QB ml/min with AVF Needle
AFN 15 G AFN 14 G
86
106
0
20
40
60
80
100
120
Volume of Processed Blood Liters
QB ml/min with AVF Needle
AFN 15 G AFN 14 G
Nephrology Dialysis Transplantation 31(Supplement1): i489–i502,2016

57. Effect of Blood Flow Rate on Adequacy
1.1
1.22
1.39
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
KT/V
Kt/V with different QB
QB 200 ml/min QB 250 ml/min QB 300 ml/min
Clinical nephrology 59(2):130-136 · February 2003
28
31 31
26.5
27
27.5
28
28.5
29
29.5
30
30.5
31
31.5
Pi Removal
Phosphate Removal with different QB
QB 200 ml/min QB 250 ml/min QB 300 ml/min

58. Adverse Effects of Conventional Thrice-Weekly Hemodialysis: Is It Time
to Avoid 3-Day Interdialytic Intervals?
Am J Nephrol 2015;41:400-408

59. LIMITATIONS OF Frequent HD
More frequent hemodialysis does not effectively clear protein-bound azotemic solutes
derived from gut microbiome metabolism Kidney international May 2017Volume 91
Relative protein binding
Azotemic compound
Relative protein binding
(%)
p-Cresol glucuronide < 40
Hippuric acid 40–50
Phenylacetylglutamine 40–50
Indoxyl glucuronide 50–60
Phenylacetic acid 60–70
Indole acetic acid 90–95
p-Cresol sulfate 90–95
Indoxyl sulfate > 95
3-carboxy-4-methyl-5-
propyl-2-furanpropanoic
acid
> 95

60. Hemodialysis Treatment Time: As Important as it Seems?
16 January 2017
Hypothetical relationship between mortality risk and weekly
dialysis time (left) or standard Kt/V

61. Extended-hours hemodialysis is associated with lower mortality risk in
patients with end-stage renal disease Kidney international December 2016Volume 90,
compare mortality risk among 1206
individuals undergoing thrice weekly
extended-hours hemodialysis or 111,707
patients receiving conventional
hemodialysis treatments
The crude mortality rate with extended-hours
hemodialysis was 6.4 deaths per 100 patient-
years compared with 14.7 deaths per 100 patient-
years for conventional hemodialysis
extended-hours hemodialysis had a
33% lower adjusted risk of death
the follow-up period for each patient was
divided into successive 91-day periods from the
date of first dialysis; follow-up was available for
up to 20 periods
Better compartmental
dialysis

62. May 2017 Volume 91, Issue 5,

64. study compared plasma concentrations of uremic
solutes in stored samples from 53 trial patients who
received three-times weekly in-center hemodialysis
for an average weekly time of 10.9 hours and ,
30 trial patients who received six-times weekly in-
center hemodialysis for an average of 14.6 hours
May 2017 Volume 91, Issue 5,

65.  Metabolomic analysis revealed that increased treatment frequency and time
resulted in an average reduction of only 15 percent in the levels of 107 uremic
solutes.
 Quantitative assays confirmed that increased treatment did not significantly
reduce levels of the putative uremic toxins p-cresol sulfate or indoxyl sulfate.
 Kinetic modeling suggested that our ability to lower solute concentrations by
increasing hemodialysis frequency and duration may be limited by the presence
of non-dialytic solute clearances and/or changes in solute production. Thus,
failure to achieve larger reductions in uremic solute concentrations may account

66. HD DOSE PRESCRIPTION AN ADEQUACY PUZZLE OR a CONFLICTING TERMS
FLUX
TIME
FREQ
UFR
MARKER?
KT/V

67. KT/V only give “1” of the “16”target of HD
1. Normalized blood pressure with minimal
antihypertensive medications
2. Normalized calcium-phosphate product with
neither phosphate binders nor phosphate
supplements.
3. An absence of intradialytic symptoms such
as hypotension, cramps, and nausea.
4. An absence of interdialytic symptoms.
5. No interference with ability to hold a job.
6. Protein appetite under the patient's free
will.
7. Neither alkalotic nor acidotic.
8. No evidence of left ventricular hypertrophy
9. Hematocrit in the 35-to-38 range with the
use of at least 50% or less of today's average
erythropoietin dose.
10. No dialysis-related or access-related
hospitalizations.
11. Normal triglyceride level.
12. No evidence of amyloidosis.
13. The longest preservation of residual kidney
function.
14. Life expectancy approximately that of living-
related-donor transplants.
15. Inflammation near normal.
16. Global cost to treat equal to less than
$45,000 per patient per year

68. What Beyond “V”
 The scaling of dialysis dose to measures of size other than body water
results in higher recommended doses of dialysis for children, small
patients, and women, compared with the current body water-based
scaling approach.
Dialysis Dosing for Chronic Hemodialysis: Beyond Kt/V
20 February 2014Full

69. Rescaling to additional parameters
AJKD March 2017Volume 69
Kt
rescaled to a
variety
normalized protein
catabolic rate (nPCR
Body surface Area
BSA
Resting Energy
Expenditure
REE
Total Energy
Expenditure
REE

70. Keeping K, t, and V Within Certain Relative Ranges
 "Kt/V is only a measure of adequate
dialysis if K, t and V are held in specific
ranges relative to each other while
achieving the KDOQI-stipulated value

71. Keeping K, t, and V Within Certain Relative Ranges
Kt/V
K is high relative to t and V
disproportionate removal of
urea relative to removal of
phosphorus, and other
important molecules
When t is low relative to K
and V
blood-pressure control
worsens, intradialytic
hypotension increases, and
mortality increases
when V is low relative to K
and t,
mortality increases

72. Rescaling for women
14%
10% 9%
21%
0%
5%
10%
15%
20%
25%
Kt/BSA Kt/TEE kt/REE Kt/nPCR
Lower Dose
Below Men
Lower Dose

73. Rescaling for small patients
9%
7%
4%
36%
0%
5%
10%
15%
20%
25%
30%
35%
40%
Kt/BSA Kt/TEE kt/REE Kt/nPCR
Lower Dose
Below Normal
Lower Dose

74. KT over REE / TEE
 It is attractive to link uremic toxin generation to Resting Energy Expenditure “ REE “
because the portion of uremic toxin generation that does not come from toxins absorbed
from the gut must come from metabolic activity in the patient’s own cells.
 REE rescaling would justify a 7.8% reduction in target dose in the elderly because the
decrease in REE with age is steeper than the decrease in V.
 Both BSA and energy expenditure rescaling support giving more dialysis to smaller
patients and to women and there are some clinical outcomes data suggesting that
women may require more dialysis than men

75. Impact of targeting Kt instead of Kt/V
K obtained By ionic Dialysance
OCM or Diascan
T is accurately calculated
the minimum Kt dose is individualized according to the body surface area (BSA)
A minimal effective Kt of 40–45 L for women or 45–50 L for men was recommended

76. This difference is particularly evident in women, in patients with a
low body weight, and in those with venous central catheters
Nephrol Dial Transplant (2013) 28 (10):

77. • dialysis dose with Kt individualized for BSA have been validated in this prospective study
in the current Spanish dialysis population, and the dose is predictably associated with
death and hospitalization risk. Prescribing an additional 3 L or more of the current Kt
individualized for BSA could reduce the risk of mortality, and an additional 9 L or more
could reduce the risk of hospitalization.
Kidney International (2016) 90, 1332–1341

78. Influence of hemodialysis
treatment parameters for
different categories of achieved–
targetKt. The bars represent the
percentage of patients on the
HDF treatment option, left axis,
for
each adjusted Kt category. The
squares (-) represent the mean
effective blood flow and the
triangles (:) the mean effective
treatment time for the patients
classified on each adjusted Kt
category, right axis
Kidney International (2016) 90, 1332–1341

79. Kidney International (2016) 90, 1332–1341

80. Scaling Hemodialysis Dose: Kt Over What?
AJKD March 2017 Volume 69,
 Focusing on sex differences, the results suggest
that:
 if dialysis were rescaled to BSA, at equivalent
levels of Kt/V, women would receive a 14%
lower dose of dialysis than men. If dialysis dose
were rescaled to REE or TEE, women would
receive a 10% or 9% lower dose, respectively,
and if dialysis dose were rescaled to nPCR,
women would receive a 21% lower dose

81. Rescaling of Dialysis Dose to BSA, REE or TEE,
or nPCR
Kt/V Kt Kt/BSA Kt/REE Kt/TEE Kt/nPCR
Male sex 1.2 49.3 25.4 30.3 25.6 51.1
Female sex 1.2 38.7 21.9 27.2 23.4 40.2
Delta, % 0 21.5 13.8 10.2 8.59 21.3
Weight > 85 kg 1.2 55.6 25.1 30.1 25.5 57.9
Weight < 62 kg 1.2 35.6 22.8 28.1 24.1 36.8
Delta, % 0.0 36.0 9.16 6.74 3.98 36.4
Age < 52 y 1.2 46.9 24.7 28.1 23.0 46.7
Age > 75.5 y 1.2 42.2 23.4 30.3 26.4 45.6
Delta, % 0 10.0 5.26 −7.83 −14.8 2.36

82. Tension Between Dialysis Patients' Desires And Nephrologists' Goals
Impact Overall Health Outcomes
Continuous diet
restriction
Fluid intake
Restrictions
HD Time difficult to
increase even a minute

83. Risk of too Much Dialysis
“how much dialysis is excessive?”
Excessive reduction of ECF
Excessive removal of beneficial
substances
Increased risk
of access
events
Accelerated
loss of residual
function
Excessive
reduction of
ECF
Microbubbles
Platelet
activation
Organ
Stunning

84. Thank you For your Attention