This document summarizes key aspects of hemodialysis adequacy and dose. It discusses: - Early studies that showed a correlation between dialysis dose and patient outcomes. The NCDS study in 1981 was the first randomized controlled trial showing higher Kt/V values were associated with better outcomes. - Methods for measuring dialysis dose including Kt/V, eKt/V, URR. The preferred method is formal kinetic urea modeling. - Guidelines recommend a minimum Kt/V of 1.2 or eKt/V of 1.2. Studies like HEMO showed no additional benefit to higher doses above 1.3-1.4. - Maximizing

1. Adequacy of Hemodialysis
By
DR. Tarek Medhat Abbas, MD
Professor of Nephrology
Urology and Nephrology Center
Mansoura University

2. Introduction

3. Global dialysis population

4. Cardiovascular mortality in general population
VS ESRD patients

5. Mortality in Hemodialysis Patients in Europe, Japan,
and the United States

6. Introduction To Adequacy
– Main target in dialysis is to improve the patient’s quality of life e.g.
• Feeling more healthy
• Less uremic complications
• Less degree of anemia
• Better control of BP
– Target can be achieved by giving your patient an adequate dose of
dialysis
– Urea Kinetic modeling is a useful tool in calculating the dose of
dialysis

7. Filters
Efficiency and Flux
• Efficiency: ability to achieve large small solute clearance with
high blood flows (all filters are high efficiency these days)
• Flux: ability to achieve high middle molecule clearance and
ultrafiltration rate (determined by the average pore size)
Diffusion and Convection
• Diffusion: solutes move by diffusion between blocks of fluid separated by the membrane
• Convection: solutes move en mass with a block of fluid across the membrane (more effective for
moving large molecules)

9. Dialysis adequacy and death
The effect of dialysis dose on
survival

10. NCDS - NEJM 1981

11. First Randomised Controlled Trial In Dialysis
• The National Cooperative Dialysis Study (NCDS) was
the first multicentric, randomized and controlled trial to
investigate the impact of dialysis dose on patients'
outcome.
• 160 patients were randomized to two different urea
time‐averaged concentrations (TAC; 100 vs 50 mg/dl) and
to two different treatment times (2.5–3.5 vs 4.5–5.5 h) and
followed‐up for 6 months.
NCDS 1980

12. First Randomised Controlled Trial In Dialysis
NCDS 1980
Predialysis urea 38 vs 26 mmol. Dialysis 2.5-35h vs 4.5-5 h
high kt/v and long
dialysis
high kt/v and short
dialysis
low kt/v and long
dialysis
low kt/v and short
dialysis

13. Secondary analysis of NCDS
• A quantification of dialysis dose using spKt/V was first
proposed by Gotch in a secondary analysis of NCDS
data.
• In his analysis, probability of dialysis failure was higher
for Kt/V ≤0.8 and abruptly decreased for Kt/V >0.9.

14. Higher Kt/V has better outcome
Gotch FA,Sargent Kidney Int 1985;28:526
Kt/v=1.2

15. NCDS Conclusion
• Thus, according to NCDS patient
morbidity and treatment failure are
related to the dialysis dose

16. Why Should We Measure Dialysis Dose?
 There is a correlation between delivered
dose of hemodialysis and patient morbidity
and mortality
 Clinical symptoms are not reliable

17. Measurement of Dialysis Adequacy

18. Measures of dialysis adequacy
• SpKt/V
• eKt/V
• StdKt/V
• URR

19.  At the end of dialysis BUN from blood (first pool).
 But not in other tissues, muscles, (the other pool).
 Organs with low blood flow (skin, bone, muscles) may serve as reservoir for
urea
 Urea then diffuses from tissues to blood to equilibrate.
 Rebound, sharp increase in urea post dialysis.
 Takes about 45- 60 minutes to complete lower Kt/V.
 Usually 0.21 less than single pool.
 Almost all centers use single pool analysis.
Single pool or double pool

20. Hemodialysis Dose Measurement
 Kt/V
K= dialyzer urea clearance L/h
t = dialysis session length hr
v = distribution volume of urea L
 URR

21. Urea reduction Ratio
(URR)
URR = 100 x (1-Ct/Co)
Ct = postdialysis BUN
Co = predialysis BUN

22. Urea Reduction Volume (URR)
 Simple
 Prediction of mortality
Limitation:
Does not account for the contribution of
UF to dialysis dose
Kt/V=1.1 (UF=0)
Kt/v = 1.35 (UF=10%BW)
URR=65

23. URR & Kt/V

24. Hemodialysis Dose Measurement
• The preferred method is by formal kinetic
urea modeling
K/DOQI 2006

25. Kt/V
Computerized software
Mathematical logarithm
Kt/v = -Ln (R-0.008t)+(4-3.5xR) x UF
W
Ln = natural logarithm
R = postdialysis BUN
predialysis BUN
UF = Ultrafiltration volume in liters
W = Postdialysis weight in kg

26.  Pre-sample: After insertion of the needle.
 Post sample :
A. To prevent rebound ; sequestration of urea from other tissues into
blood to reach equilibrium less than 2 min after ending,
B. To prevent recirculation ; blood pump is slowed to 30 ml/min for
one minute and a sample is taken from art. line.
BUN SAMPLING OF KT/V &URR

27. Post Dialysis BUN Sampling
Avoid 2 rebound:
Early (<3min post dialysis)
 Access recirculation,begin immediately post
hemodialysis and rebound in 20 seconds
 Cardiopulmonary recirculation, begin 20 seconds
post hemodialysis and is completed in 2-3 minutes
after slowing or stopping the blood pump.
Late (>3 min)
 Completed within 30-60 minutes due to flow-volume
disequilibrium.

28. Urea Rebound
65% rebound ( >50% is AR,15%CP,31% D)

29. Equilibrated Kt/V
 eKt/v is 0.2 units less than single-pool kt/v, but it can be as great 0.6
unit less.
 For most patient, urea rebound is nearly complete in 15 minutes
after hemodialysis but for minority, it may require up to 50-60 minutes
 The degree of rebound is high in small patient
• eKt/V= spKt/V - 0.6 x (spKt/V) / t + 0.03 (for arterial access)
• eKt/V= spKt/V - 0.47 x (spKt/V) / t + 0.02 (for venous access)

30. Solute Removal Index
American Journal of Kidney Diseases, Vol 38, No 6 (December), 2001: pp 1277-1283

31. Minimum dialysis dose
• SpKt/V > 1.2 US
• eKt/V > 1.2 Europe
• StdKt/V 2.14

32. Higher Kt/V: does it make a difference?

33. Daugirdas Formula

34. DEFENITION of Kt/V
• K= urea clearance of a dialyzer
– This depends on two factors
• the ability of the hollow fiber to clear urea
– The pore size and specification
– The surface are of the dialyzer
• The rate of blood flow through the hollow fiber
– Supplied by manufacturer and should be checked
• t =during a certain time of dialysis (minutes)
• V =Volume of dissolved urea in the body
– urea is equally distributed in all body compartments
– water is also equally distributed in all body compartment Volume of urea almost equals
total body water

36. How to calculate V or
Total Body Water (TBW)
• Simplest: 2/3 of body weight
• Bio-Electrical Impedance
– Elctrical Measurement of TBW
• Kinetic measure for TBW
• Anthropometric measures
for TBW
TBW = -0.07493713 x age - 1.01767992
x male + 0.12703384 x ht
-0.04012056 x wt + 0.57894981
x diabetes - 0.00067247
x wt2 - 0.03486146 x (age x male)
+ 0.11262857 x (male x wt)
+ 0.00104135 x (age x wt)
+ 0.00186104 x (ht x wt)

37. Calculate the dose of Dialysis
• K= clearance of hollow fiber
– Available from producer
– Urea clearance for a given blood flow
• V= Calculated by any method
– Weight, height, age, gender ..etc
• You decided on the duration of dialysis
– t= time expected on dialysis in minutes
CALCULATE DOSE OF DIALYSIS =Kt/V

38. Dose of dialysis
• Depends on three factors
– 1. The time of dialysis (t) 
– 2. The amount of urea a hollow fiber can clear when blood
passes through it (K) 
– 3. The total volume of urea in the patient’s body that needs
to be dialyzed (V) 
Kt/V= dose of dialysis

39. Automated monitoring of hemodialysis
adequacy by dialysis machines
• Has potential benefits to patients and cost savings
• Kidney International 2010 78, 833-835

40. Automated monitoring of hemodialysis
adequacy by dialysis machines

41. What Happens if a smaller dose is given?
Worse outcome :
• Death
• Fall in albumin level
• Hospitalization (not related to access)
• Infections

42. Prescribed vs. delivered Kt/V
Prescribed Kt/V is a computerized
estimation of what the patients Kt/V would
be, based on the prescription
Delivered Kt/V is actual results based on
how the patient really dialyzed the day the
kinetic labs were drawn

43. How to make sure patient has actually received his dose of
dialysis
Delivered KT/V
• Variables Used
• R= BUN before -BUN after
• UF/W= wt removed during Dx/ post Dx weight
– Deducted using one of the following formulas
a. 2.2 - 3.3x (R - 0.3 - UF/W) (bedside)
b. -ln(R-0.3) + (4-35xR) x UF/W (logarithmic)
• Daugirdas JT in Daugirdas and Ing in Handbook of dialysis Little Brown and Co 2nd ed

44. Discrepancies Between Delivered and Prescribed
Dialysis Dose
Delivered less than the prescribed:
 Low blood flow
 Inadequate dialyzer performance
 Low dialysate flow
 Dialysis machine programmed incorrectly
 Hemodialysis ended prematurely
 The predialysis BUN was drained after
initiation of hemodialysis
 Access recirculation
 Weak vascular access

45. Low kt/v

46. How to improve clearance
• Blood flow
• Dialysate flow
• Dialyzer
• Duration
• frequency

47. Blood flow and Clearance

48. Blood flow and Clearance

49. Dialysate flow and clearance

50. Discrepancies Between Delivered and Prescribed
Dialysis Dose
Delivered Dose More than the Prescribed:
 Postdialysis BUN was drained from venous
bloodline
 The post dialysis BUN was diluted with saline
 Small (V)

51. THE HEMO STUDY (2002)
• 1846 patients under hemodialysis

52. The HEMO Study (2002)
Standard dose group
• SpKt/V 1.3
• eKt/V 1.16
• URR 66.3
• Dialysis T 190 min
High dose group
• SpKt/V 1.7
• eKt/V 1.53
• URR 75.2
• Dialysis T 219 min

53. The HEMO Study (2002)
• Tests for outcome:
– Death
– Fall in albumin level
– Hospitalization (not related to access)
– Infections
• Results of outcome were the same in the two groups

54. The HEMO Study (2002)

55. The HEMO Study (2002)
EKNOYAN et al N Engl j Med.2002 ;347:2010

56. Conclusions Of HEMO
• Dialysis prescription of KT/V Values less than 1.2 may
carry a high mortality and morbidity
• Increasing the dose of dialysis of a KT/V more than 1.4
does not carry any significant benefit
• Recommended dose is a KT/V which lies between 1.3
and 1.4 (single pool)
• No benefit from the use of high Flux dialyzers

57. Standard Kt/V

58. Standard Kt/V
why Hemo study is negative ?

59.  Complex, may be difficult to understand.
 Urea is not associated with toxicity.
 It assumes urea diffusion across the membrane is comparable to other
toxins.
 Dosing is depends on V (TBW),V in females is < V in males with the
same surface area lower calculated dose.
 Kt/V is a poor measure of control of extracellular fluid overload, and it
certainly does not reflect the rate of fluid removal.
 Kt/V urea does not reflect control of serum phosphorus;
Criticism of KT/V

61. Optimal Dialysis
Anemia
management
Good nutritionBP control
Adequate
solute
removal
Fluid and
electrolytes
hemostasis
BMD
management
Dialysis
adequacy

62. What are the objectives?

63. GOALS?

64. How can we reach our Goals?

65. Educate Your Patients

66. Frequency of dialysis:
• Thrice, quotidian
• every other day
• Daily in-center
• Daily Home Dialysis
• Nocturnal Dialysis
• In–center Nocturnal Dialysis
• Other

68. FHN

71.  Reflects protein intake in steady state patients.
 Increased kt/v leads to increase in PCR and more protein intake.
 nPCR is of great value predicting morbidity.
 Adequate Dx recommended > 1.1 gm/kg/day
Normalized protein catabolic rate IMPORTANCE

72. Residual Renal Function (Kr)
Effect on KT/V and URR
• Has insignificant effect on urea clearance during hemodialysis
• But has a significant effect on lowering predialysis BUN
• Every 1ml/min of Kr offers a KT/V of 0.13
• Consequently patients with Kr needs less KT/V but don’t
decrease dialysis dose

73. Residual renal function

74. Time is important

77. European Best Practice Guidelines

78. EBPG on Hemodialysis update

79. EBPG on Hemodialysis update

80. Maximize Middle Molecule Removal
1. Use High Flux membranes (more permeable membranes for larger toxins).
2. Apply more convection, i.e. Haemodiafiltration (HDF).

81. B2 Microglobulins

82. Reduced ß2-microglobulin levels
F Locatelli et al, Kid Int, 50: 1293-1302, 1996.
Lower incidence of CTS / amyloidosis
F Locatelli et al, Kid Int, 55: 286-293, 1999.
J. Berland et al, NDT, 10 (Suppl.10): 45-47 (1995).
Improved safety (endotoxin retention)
Grötsch et al & Weber et al, Dialyse J, 1998
Improved lipid status
P J Blankestijn et al, JASN, 5: 1703-1708, 1995
P B Forster et al, NDT, 14 (Suppl. 4) 49-51, 1999.
Lower mortality risk
F Port, USRDS; ASN 1998.
Treatment with high flux

84. The MPO Study (2009)
Significance:
• Large, randomized clinical outcomes trial for 3x/week intermittent HD for incident patients
• Compared low versus high flux filters (Kuf, β2M-sieving coefficient) with equal urea Kt/V
• Stratified patients based on albumin (≥4 g/dL or <4 g/dL)
Conclusions:
• “In summary, we did not detect a significant survival benefit with either high-flux or low-flux
membranes in the population overall,
• The use of high-flux membranes conferred a significant survival benefit among patients with
serum albumin <4 g/dl.
• “the results of the MPO Study can be interpreted as a supporting rationale for the use of high-
flux dialysis membranes if they are financially affordable.”

85. Comparison between predialysis PTH for patients with low flux and
high flux dialysis membranes
Ahmed Rabie El Arbagy et al. Study of Effect of High-Flux Versus Low-Flux Dialysis Membranes on Parathyroid
Hormone. American Journal of Clinical Medicine Research, 2014, Vol. 2, No. 1, 36-42. doi:10.12691/ajcmr-2-1-9
© The Author(s) 2014. Published by Science and Education Publishing.

86. KDOQI CLINICAL PRACTICE GUIDELINE

87. KDOQI Clinical Practice Guideline for Hemodialysis Adequacy: 2015 Update
John T. Daugirdas, MD, Thomas A. Depner, MD, Jula Inrig, MD, MHS, Rajnish Mehrotra, MD, Michael V. Rocco, MD, MSCE, Rita S.
Suri, MD, MSc, FRCPC, Daniel E. Weiner, MD, MS, Nancy Greer, PhD, Areef Ishani, MD, MS, Chief, Roderick MacDonald, MS, Carin
Olson, MD, MS, Indulis Rutks, BS, Yelena Slinin, MD, MS, Timothy J. Wilt, MD, MPH, Michael Rocco, MD, MSCE, Holly Kramer, MD,
Michael J. Choi, MD, Milagros Samaniego-Picota, MD, Paul J. Scheel, MD, MBA, Kerry Willis, PhD, Jessica Joseph, MBA, Laura
Brereton, MSc John T. Daugirdas, MD, Thomas A. Depner, MD, Jula Inrig, MD, MHS, Rajnish Mehrotra, MD, Michael V. Rocco, MD,
MSCE, Rita S. Suri, MD, MSc, FRCPC, Daniel E. Weiner, MD, MS, Nancy Greer, PhD, Areef Ishani, MD, MS, Chief, Roderick
MacDonald, MS, Carin Olson, MD, MS, Indulis Rutks, BS, Yelena Slinin, MD, MS, Timothy J. Wilt, MD, MPH, Michael Rocco, MD,
MSCE, Holly Kramer, MD, Michael J. Choi, MD, Milagros Samaniego-Picota, MD, Paul J. Scheel, MD, MBA, Kerry Willis, PhD, Jessica
Joseph, MBA, Laura Brereton, MSc
American Journal of Kidney Diseases
Volume 66, Issue 5, Pages 884-930 (November 2015)
DOI: 10.1053/j.ajkd.2015.07.015
Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions
KDOQI Clinical Practice Guideline for
Hemodialysis Adequacy: 2015 Update

88. Figure 2
American Journal of Kidney Diseases 2015 66, 884-930DOI: (10.1053/j.ajkd.2015.07.015)
Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

89. Timing of Hemodialysis Initiation
• Education about different forms of renal replacement therapy (RRT)
should be started once eGFR reaches <30 mL/min/1.73m2 or the
eminent need for RRT approaches. No change from 2006. (No grade)
• The timing of therapy should be driven by signs and symptoms of
uremia, evidence of protein-energy wasting, or metabolic
abnormalities/volume overload refractory to medical management.
The 2015 guideline removes any suggested eGFR (which was
previously given as 15 mL/min/1.73m2 in 2006). (No grade).

90. Frequent and Long Duration Hemodialysis
In-center Frequent HD
• Suggest: Patients with ESRD should be offered in-center short frequent
HD as an alternative to thrice weekly HD, with discussion of patient
preference and risk/benefit. Not in 2006 guideline. Grade of 2C.
• Recommend: All patients need to be informed of risk of in-center frequent
HD, including increase in vascular access complications and potential
hypotension during HD. Not in 2006 guideline. Grade of 1C.

91. Home Long HD
• Consider home long HD for patients with ESRD who
prefer this therapy for lifestyle considerations. Not in
2006 guideline. (No grade).
• Recommend: All patients need to be informed of risk
of home long HD, including increase in vascular
access complications, potential for increased
caregiver burden and accelerated decline of residual
kidney function. [Not in 2006 guideline]. (Grade 1C).

92. Pregnancy
• During pregnancy, women with ESRD should receive
long frequent HD either in center or at home.
Not in 2006 guideline. No grade given.

93. Measurement of Dialysis: Urea Kinetics
• Recommend: Target single pool Kt/V of 1.4 and minimum Kt/V of 1.2 per HD
session in thrice weekly HD. No change from 2006. (Grade 1B).
• Dose may be reduced in patients with significant residual kidney function
provided residual kidney function is measured periodically. No change from
2006. (No grade).
• For schedules other than thrice weekly, suggest a target Kt/V of 2.3 volumes
per week with minimum Kt/V of 2.1 using a method of calculation that includes
ultrafiltration and residual kidney function. Not in 2006 guideline. (No grade).

94. Volume and Blood Pressure Control: Treatment
Time and Ultrafiltration Rate
• Recommend: Patients with low residual kidney function
(<2mL/min) undergoing thrice weekly dialysis need a
minimum of 3 hours per treatment. No change from
2006. Grade of 1D.
• Consider longer session or extra session if large
weight gains, high BP, high UF rates, metabolic
complications, or inability to achieve dry weight. No
change from 2006. No grade given for this

95. Volume and Blood Pressure Control: Treatment
Time and Ultrafiltration Rate
• Reduce dietary sodium intake and ensure adequate
sodium/water removal with HD to manage HTN and
volume. Grade of 1B.
• Prescribe UF rate balancing risk of hemodynamic
instability with benefit of volume removal. No change
from 2006. No grade

96. Adequacy QI Team

97. Guides to dialysis prescription
• Patient weight
– dry weight
– IDWG
• Co-morbidities.
• Recent lab work.
• Medications.
• Current clinical condition.
• Dietary status
• Mode

98. Basic goals of adequate dialysis:
Fluid removal to expected 'dry weight' at end of dialysis.
Predialysis BP < 140/90 mmHg with or without antihypertensive drugs.
Predialysis plasma concentrations:
-Potassium: ≤5.5 mmol/l without using ion exchange resins.
-Bicarbonate: ≥24 mmol/l .
-Inorganic phosphate: ≤5.5 mg/dl without oral binding agents.
-Urea: <35 mmol/l with daily protein-intake1.2 g/kg/BW .
-Albumin: ≥40 g/l & Cholesterol= 200-300 mg%
-Haemoglobin: 11–12 g/100ml with or without ESA.
Rodriegaz handbook of dialysis 2012

99. TECHNICAL REQUIREMENTS FOR DELIVERY OF ADEQUATE DIALYSIS:
Vascular access: blood flow ≥ 300 ml/min .
Dialysis fluid: bicarbonate buffered, sterile, pyrogen-free.
Volumetric machine.
Dialyzer: -Highly permeable, biocompatible membrane.
- Surface area: ≥1.3 m2.
Dose of dialysis:
-Minimum Kt/V urea: 1.2–1.3 (single pool).
-Minimum URR : 65–70%.
-Measurement of dialysis dose: once / month.
- Weekly dialysis time:
- HD Vs HDF
Rodriegaz handbook of dialysis 2012

101.  Kt/V > 1.3.
 TAC < 52.
 PCR >1.1 gm/kg/day.
 Good nutritional indices:
• plasma albumin >4 gm%.
• pre Dx BUN= 70-90mg%.
• Hemoglobin level >11 gm.
 Minimal degree of dialysis complications.
Ideal dialysis patient:

102. THANK YOU