HD - Hemoperfusion

Kidney Int Suppl (2011). 2022 Apr; 12(1): 7–11.

TYPES OF BLOOD
PURIFICATION ON ESKD
 Limits of Conventional
Hemodialysis
Calcinosis cutis Vascular calcification

ß2-microglobulin amyloidosis
Muscle wast
Contracting
 I NDONESIAN RENAL PENYEBAB KEMATIAN PASIEN HD
REGISTRY DI INDONESIA TAHUN 2018

K6 (Tidak Diketahui)
31%

K1 (Kardiovaskuler)
42%
Kelainan kardio-
serebrovaskuler 50 %
K5 (Penyebab Lain)
K4 ( Sepsis)
6%
10%

K3 (Perdarahan K2 (Serebrovaskuler)
Saluran Pencernaan) 8%
3%
 Most Common
Complications Related to ESKD
• Anemia
• Uremic pruritis (itching)
• Amyloidosis
• Refractory hypertension
• Secondary Hyperparathyroidism
• Sleep disturbances
• Death
Classification of Waste Products in Blood
Small Molecular Weight
(SMW)
< 500 D

Middle Molecular Weight

(MMW)
500 – 12,000 D

High Molecular Weight

(LMW)
>12,000 D
TYPES OF BLOOD PURIFICATION ON
ESKD
 Small water-soluble compounds
 <500D
HD/HDF
 Serum Creatinine
 Easily removed by whatever type of dialysis

 Middle molecule Toxins

 >500D
HDF/
 β
2-macroglobulin, PTH HD+HP

 Protein bound uremic toxins HDF/

 indoles, phenols HD+HP
 - EUROPEAN UREMIC TOXIN WORK GROUP

At present, about 90 different uremic toxins have identified, and this number certainly represents only a
minority of toxins that accumulate during chronic renal failure and contribute to the uremic syndrome

LOW FLUX
High performance HIGH FLUX HEAMOFILTER Protein Bound +lipid solvable
5000 Da 16000 Da 30,000Da 5000 -30,000Da

Low-Flux High-Flux HV-HDF

Diffusion
Low-Flux Diffusion
High-Flux Convection
HV-HDF
Molecular Uremic Toxins Convection
Diffusion Diffusion
+HP (Adsorption)
Weight (examples)
Yes Yes YES
Water-soluble (non-protein bound)
Yes Yes Yes
Small Molecular Weight urea (60D), creatinine (113) YES YES YES
(SMW)
< 500 D
Protein Bound
EUTox group identified at least 22 middle m olecules, of which 12 have a MW >12,000D a – substantial number of these bioactive molecules are linked to inflammation, oxidative stressNo, malnutrition andardiovascular diseaNose No
P-cresol (108D), homocysteine c
YES Yes YES
Middle Molecular Weight Β2m (11.8 D), AGEs (10 kDa), Parathyroid Yes
(MMW)
500 – 12,000 D hormone (9,223D) Yes
No Limited
YES YES YES
High Molecular Weight Leptin (16D), Complement factor D (protein
(LMW)
>12,000 D 24kD)
No No No
A TREATMENT THAT IS NEAR TO NATURAL KIDNEY
IN ELIMINATING TOXINS?
Normal Kidney function
 Small Uremic Toxin
HD/HDF Part of the uremic toxin
+
1.0 HP
 Protein-bound Uremic Toxin
Ideal combination
Adequate removal of all Middle
Uremic Toxin

 High Molecular Weight (LMW)

0.5

0 10 20 30 40 50 60 70 • 20 years of clinical experience

Molecular weight in 103 • More than 3 million treatments per year
Extracorporeal Sorbent Technologies:
Basic Concepts and Clinical Application
William R. Clark .Fiorenza Ferrari Gaetano La Manna ,Claudio
.

Ronco
The Principle of Hemoperfusion
Adsorbent

Adsorption
SORBENT
E x t r a c or p or e a l S o r b e n t Technologies: Basic C on c e p t s a n d Clinical A p p l i c a t i o n
William R. Clark ..Fiorenza Ferrari Gaetano La Manna ,Claudio Ronco

Biocompatibility of Sorbents
HD-HP  THE SURFACE DEFINES THE PERFORMANCE
Membrane- filter Resin- Jafron HAadsorber

Overall surface≈ 2sqm HA130 Overall surface ≈ 20,000 sqm

Possible Modes of Application of Sorbents

Kidney International, Vol. 58, Suppl. 76 (2000), pp. S-148–S-155

 HD – HP :
Clinical Indications
• PTH> 300 pg/mL and or β2-m group ≥ 30 mg/L
• Uremic syndrome :
 Uremic pruritis
 Secondary Hyperparathyroidism
 Dialysis-related amyloidosis
Contraindications:
 Resistance hypertension
 Sleep disorder - Platelet <60 × 109/L
- Bleeding (lysis)
- Hypotension : BP <90/60 mmHg
- Allergic to hemoperfusion materials
 Hemoperfusion For ESKD in
Maintenance
Dialy
sis Treatment For Treatment mode Subsistence can be Eliminated

HA130 Long time complications uremic Treatment /Machines Proton bounded , Middle & High
toxins : Modes: molecular weight toxins:
🟢 Beta 2 macroglobulin
Adsorbent resin Double cross linked styrene 🟢 Leptin
type divinylbenzene copolymers.
🔴 Cardiovascular Diseases ✅ Low flux HD
🔴 Chronic inflammatory ✅ High Flux HD 🟢 Interleukins, C reactive proton ,
Cut off 5000 Da- 30000Da
reactions ✅ HDF post dilution tumour necrosis factor
Priming Volume 100 +/- 20ml
🔴 Malnutrition ✅ High volume HDF 🟢 Advanced glycation end
Resin V 130 ml
🔴 Renal Osteodystrophy products (AGEs)
Surface Area 18000-20000 🟢 parathyroid hormone
🔴 Carpel Tunnel syndrome
Sterilized by Gamma Irradiation
🔴 Uremic Pruritis 🟢 Renin Angiotensin
Housing polycarbonate
Material 🔴 Refractory Hypertension
 Study on
Hemoperfusion Combined with Hemodialysis
 Research Article

Blood Purif Received: March 22, 2022

Accepted: April 19, 2022
DOI: 10.1159/000525225
Published online: August 11, 2022

Randomized Control Study on Hemoperfusion

Combined with Hemodialysisversus Standard
Hemodialysis: Effectson Middle-Molecular-Weight
Toxinsand Uremic Pruritus
SHANGHAI MULTICENTER RCT : PRIMARY RESULTS

Lower PTH

Lower B2-MG
SHANGHAI MULTICENTER RCT : PRIMARY RESULTS

Lower overall Mortality

Lower CV Mortality
BEIJING MULTICENTER RCT National science and technology support RCT program

Eligible patients (n=440)

LFHD group HFHD group LFHD+HP group HFHD+HPgroup

n=110 n=110 n=110 n=110

3 HD/W，4h each 2 HD+1 HD+HP/ W

Jafron HA130 hemoperfusion combined with low-flux hemodialysis

 Good performance on safety
 It significantly reduces β2-MG , PTH, and improves pruritus. It is superior to high-flux hemodialysis
 Provides a simple, easy and effective blood purification mode for the basic medical institutions
BEIJING MULTICENTER RCT: PRIMARY RESULTS

Comparison of iPTH changes over 12 Comparison of β2-MG changes over 12 months

months

 After 12 months of treatment, significant decline rate of iPTH.

 After 12 months of treatment, significant decline rate of β2-MG .
 After 12 months of treatment, significant improvement of pruritis score
HD+HP AND UREMIC PRURITIS
Pruritus/Itching is a common problem for patients
with chronic renal failure or end stage renal disease. It
affects about one-third of patients on dialysis.

Uremic pruritus is associated with a 17% increase in

mortality
Causes of uremic pruritis
• Dry skin
• Reduced sweating
•Abnormal metabolism of calcium and phosphorus / Most common: back, abdomen, head and /or arms
raised parathyroid hormone (PTH)
Management:
• Accumulation of toxins
- Optimizing dialysis efficacy
• Sprouting of new nerves
- Reduce serum parathyroid hormone
• Systemic inflammation
- Cleansers and creams
•Co-existing medical problems, particularly diabetes
- UVB phototherapy for severe uremic pruritus
and liver disease.
- Others…
HD+HP AND UREMIC PRURITIS
1. Reduce uremic toxins (PTH, β2-MG) [1,2]
3. Improve pruritis Score [3]

2. Improve systemic inflammation [1,2]

Reduce uremic toxins specially

PTH, regulate the systemic
inflammation and thus
improve the uremic pruritis

1 Huu, Dung Nguyen, et al. "A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A
Pilot Study in Vietnam." Blood purification: 1-8.
2 Chen, Shun-Jie, et al. "Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney." The International journal of artificial
organs 34.4 (2011): 339-347.
3 Gu, Yan Hong, et al. "Additional hemoperfusion is associated with improved overall survival and self-reported sleep disturbance in patients on hemodialysis." The International
journal of artificial organs 42.7 (2019): 347-353.
HD+HP AND AMYLOIDOSIS
•Dialysis-related amyloidosis(DRA) is a serious complication of
long-term dialysis therapy and is characterized by the deposition of Carpal tunnel syndrome
β2 microglobulins (β2MG) in the osteoarticular structures and viscera.

• Prevalence:
• DRAcan be seen in as much as 20% of patients after 2–4 y ears of
HD and in 100% of patients after 13 years of HD [1].
• DRAmainly involves the osteoarticular system
• (bone, synovium, muscle, tendon, ligaments)

• Main clinical events of β2-MG

 Carpal tunnel syndrome (CTS) typical “guitar string sign”, the prominence of
shrunken flexor tendons (see arrows)
 Bone cysts
 Scapula–humeral periarthritis
 Joint arthropathy [1]Jadoul M, Garbar C, Noël H, et al. Histological prevalence of beta 2-microglobulin amyloidosis in hemodialysis: a prospective
postmortem study. Kidney Int. 1997;51(6):1928–1932.

 Destructive spondyloarthropathy
 HD+HPAND RESISTANT HYPERTENSION

Resistant/Refractory hypertension:

• Hypertension is present in more than 80% of ESRD cases .

• More than 70% of hypertensive patients in chronic HD programs are not
efficiently controlled.
• The target blood pressure (BP) values of < 140/90 mmHg in order to reduce
cardio-vascular morbidity and mortality in dialysis patients.

1 Agarwal R. Hypertension in chronic kidney disease and dialysis: pathophysiology andmanagement. Cardiol Clin. 2005;23:237–248.
2 Agarwal R, Flynn J, Pogue V, et al. Assessment and management of hypertension in patients on dialysis. J Am Soc Nephrol. 2014; 25:1630.
 HD+HPAND RESISTANT HYPERTENSION
1. Reduce the Renin-Angiotensin II- Aldosterone levels
2. Reduce the SBP and DBP

Lu sheng et al Chin J Blood Purif, May,2015,Vol.5,No.14

 HD+HPAND SECONDARY HYPERPARATHYROIDISM

Secondary hyperparathyroidism (SHPT):

Common complication of chronic kidney disease characterized by
elevated parathyroid hormone levels secondary to derangements in the
homeostasis of calcium, phosphate, and vitamin D.

SHPT is associated with increased cardiovascular morbidity and

mortality

HD + HP could reduce the PTH and phosphorus levels

and thus may improve the symptoms and prevent
progression of the secondary hyperparathyroidism [1,2]
Fig.1 Secondary hyperparathyroidism
in advanced chronic kidney disease [3]

1 Chen, Shun-Jie, et al. "Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney." The International journal of artificial organs 34.4 (2011): 339-347.
2 Huu, Dung Nguyen, et al. "A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A Pilot Study in Vietnam." Blood purification: 1-8.
3 Waziri, Bala, Raquel Duarte, and Saraladevi Naicker. "Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD): Current Perspectives." International Journal of Nephrology and Renovascular Disease 12 (2019): 263.
HA+HP AND SLEEP DISTURBANCES
Sleep disturbances are extremely common among dialysis patients.
Sleep complaints are reported in up to 80% of CKD patients [1,2].

Most common causes:

 Chronic pain
 High levels of parathyroid hormone (PTH)
 Uremic pruritis ?
 Low secretion of melatonin
 Higher rates of anxiety and stress
 Socioeconomic status

Most common complaints included

 Falling asleep (daytime)
 Nighttime awaking
 Early morning awaking
 Restless legs
 Jerking legs

1 Merlino G. Piani A. Dolso P. Adorati M. Cancelli I. Valente M. Gigli G. L. 2006Sleep disorders in patients with end stage renal disease undergoing dialysis therapy. Nephrol Dial Transplant; 21 184
2 Iliescu E. A. Coo H. Mc Murray M. H. Meers C. L. MM Quinn MA Singer Hopman W. M. 2003Quality of sleep and health-related quality of life in haemodialysis patients.
Nephrol Dial Transplant 18 126 132
HD+HP AND SLEEP DISTURBANCES
 Reduce PTH levels
 Increase Melatonin levels
 Relieve pruritis
 Improve sleep duration and efficacy

Fig.2 Comparing nocturnal melatonin value

between HD and HD + HP groups before and
after 24-month follow-up period [1]

Table.1 comparison between sleep related marker between the tow groups [1]

[1] Gu, Yan Hong, et al. "Additional hemoperfusion is associated with improved overall survival and self-reported sleep disturbance in patients on hemodialysis." The International journal of artificial organs 42.7 (2019): 347-353.
HD+HP AND INTESTINAL MICROBIOTA

Microbiota in HD patients

 Improve CRP
 High level of Lactobacillus acidophilus
 Low levels of Escherichia

Figure 1: Levels of Bifidobacterium, Lactobacillus acidophilus,

Escherichia coli, and Enterococcus faecalis.Effect of different
hemodialysis methods on intestinal flora. ∗P < 0:05. [1]

[1] He, Haidong, and Yan Xie. "Effect of Different Hemodialysis Methods on Microbiota in Uremic Patients." BioMed Research International 2020 (2020).
 HA130 AND PROTIEN
BOUND TOXINS
 Efficiently reduce protein
bound uremic toxins such as
indoxyl sulphate and p-cresol

 May reduce the cardiovascular

events caused by this kind of
toxins and reduce the mortality

Panichi, Vicenzo. “Removal of protein bound toxins in dialysis patients: A pilot study using hemoperfusion” 57 th ERA-EDTA Congress, 6 June 2020, Online. lecture.
https://www.youtube.com/watch?v=dtjPkYiXX6o&t
HD+HPAND QUALITY OF LIFE

Improve
 Body pain
 General health
 Vitality
 Emotional role
 Mental health
 Total QoL score

* Compared to control group, p<0.05

Chen, Shun-Jie, et al. "Combination of maintenance hemodialysis with hemoperfusion: a safe and effective model of artificial kidney." The International journal of
artificial organs 34.4 (2011): 339- 347.
HD+HPAND SURVIVAL RATE
Follow up for 3 years

Reduce uremic toxins may reduce the

cardiovascular events and increase the
survival rate
Follow up for 2 years

Fig.1 survival curve after 24 months of observation [1]

Patients in the HD+HP group exhibited a significantly higher
survival rate compared with the HD (log-rank test, p = 0.049) [2].

1 Gu, Yan Hong, et al. "Additional hemoperfusion is associated with improved overall survival and self-reported sleep disturbance in patients on hemodialysis." The International journal
of artificial organs 42.7 (2019): 347-353.
2 Huu, Dung Nguyen, et al. "A Combination of Hemodialysis with Hemoperfusion Helped to Reduce the Cardiovascular-Related Mortality Rate after a 3-Year Follow-Up: A
Pilot Study in Vietnam." Blood purification: 1-8.
SUMMARY OF HD+HP

 Removing of middle uremic toxins

 Release complications
- Itching
- Sleep disturbances
- Bone pain
- Resistant hypertension
- SHPT
 Improving life quality
 Benefit survival
A schematic diagram of haemodialysis (HD) + haemoperfusion (HP) treatment.

Lu W, Jiang G-R. BMJ Open 2018;8:e022169