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Dialysis Options in Special Conditions:

Hemoperfusion for
Sepsis and SA-AKI

Grace Zhang
Jafron Biomedical Co., Ltd., China
Causes of AKI

2012 KDIGO
Mechanism of Sepsis
Microbial insult(Endotoxin-LPS/endotoxin-peptidoglycan)

Pro-inflammatory state

Complement and Protease activiation: Free Cytokine secretion: Cellular involvement:


coagulation Heparin sulfate, radical IL-1, IL-6, Neutrophils, macrophages, DG,
pathway activiation hyaluronic acid, elastase formation PAF, TNF-a platelets, endothelial cells

Anti-inflammatory state

Increased Poor Deranged immune Impaired Lymphocyte


IL-10 Phagocytosis function chemotaxis apoptosis

Mitochondrial dysfunction Metabolic acidosis Oliguria Endothelial dysfunction


Apoptosis and necrosis Capillary leakage Thrombosis Impaired vascular tone

Sepsis Associated Acute Kidney Injury(SA-AKI), Multiple Organ Failure(MOF) & Death

Zarjou A, Agarwal A. Sepsis and acute kidney injury. Journal of the American Society of Nephrology Jasn, 2011, 22(6): 999-1006.
Common blood purification methods

N=60 SA-AKI patients MAP Heart Rate


Group No. APACH II Score
(mmHg) (Times/min)
Group (IHD) n=30
Group (CRRT) n=30 Group(IHD)
Group(CRRT)
t value
P value
Result:
Tab.1 Comparison of APACH II score between two groups of patients with different AKI stages pre and post treatment
I stage II stage III stage
Group No.
Pre-treatment Post-treatment Pre-treatment Post-treatment Pre-treatment Post-treatment
Group(IHD)
Group(CRRT)
t value
P value

• IHD and CRRT are effective for patients with SA-AKI.


• Compared with IHD, clinical effect of CRRT for SA-AKI is better.

Contemporary Medical Symposium, 2018, Vol.16, No.21


Restriction of filters

β2-MG:3.442nm

10 times The pore size of high-flux dialyzer is not


large enough for middle molecules.

Pore size:20-50nm
Inflammatory mediators

hemodialysis / - filtration hemoperfusion


Adsorption Therapy--Principle
HA330 for Critical Disease
Removal of inflammatory mediators and cytokines

Indications Treatment Modes


Safety of Jafron Cartridges

Methods:
• Monocytes were exposed to the sorbent material in static and dynamic manners.
• In static test, cell medium samples were collected after 24 h of incubation in the cartridges.
• In dynamic test, HP modality has been carried out and samples at 30, 60, 90, and 120 min were collected.
Safety of Jafron Cartridges

Results:
Compared to control samples,
there was no evidence of
increased necrosis or
apoptosis in monocytes
exposed to the cartridges both
in the static and dynamic tests.

Conclusion:
Our in vitro testing suggests that HA cartridges carry an optimal level of biocompatibility and
their use in HP is not associated with adverse reactions or signs of cytotoxicity.
HA330 for Sepsis
Design:
A prospective randomized, parallel
controlled analysis.

N=46
N(Control)=21
standard therapy included
fluid resuscitation, vasopressors,
antimicrobial therapy, ventilatory, etc.

N(HP)=25;
HP once a day for three consecutive
days after admission to the intensive
care unit.& standard therapy

Follow-up:28 days

Outcome:
• Cytokines
• Organ Function
• Survival

Zhao Huang et al. Therapeutic Apheresis and Dialysis, 2012: 1744-9987


HA330 for Sepsis

HP decreases IL-1 & TNF-a.

Zhao Huang et al. Therapeutic Apheresis and Dialysis, 2012: 1744-9987


HA330 for Sepsis

HP improves organ function and hemodynamic

Zhao Huang et al. Therapeutic Apheresis and Dialysis, 2012: 1744-9987


HA330 for Sepsis

HP benefits survival rate.

Zhao Huang et al. Therapeutic Apheresis and Dialysis, 2012: 1744-9987


HA330 for SA-AKI

Design:
A prospective randomized, controlled analysis.

N=40
N(Control)=18
standard therapy

N(HP)=22;
HP once a day for three days, each session lasts 2h

Follow-up:2 weeks

Outcome:
• Cytokines
• Organ Function

Huang Zhao etc. China J Emerg Med, January 2011, Vol. 20, No.01
HA330 for Sepsis Induced AKI

HP decreases inflammatory mediators.

Huang Zhao etc. China J Emerg Med, January 2011, Vol. 20, No.01
HA330 for Sepsis Induced AKI

Renal function obviously


improved in HP Group.

Huang Zhao etc. China J Emerg Med, January 2011, Vol. 20, No.01
HA330 for Sepsis Induced AKI

Huang Zhao etc. China J Emerg Med, January 2011, Vol. 20, No.01
From Single to Hybrid
HD/CVVH… Hemoperfusion
• Strengths: effective clearance of water- • Strength: effective clearance of medium-to-
soluble and low protein substances, correct macro, protein-bound toxins and fat soluble
water-electrolyte imbalance. substances.
• Weakness: inefficiency clearance of macro
• Weakness: it can not regulate water-
molecules and fat soluble toxins.
electrolyte, acid-base balance.

HP+CVVH/HDF/HD/…
HDF+HP VS CVVH for SA-AKI

Design:
A prospective randomized, parallel controlled analysis.
Tab.2 Changes of APACHE II
N=58
N(control)=29 APACHEII
Standard therapy + CVVH treatment for 24h Group Pre- 7 days 14 days
treatment post treatment post treatment
N(HDF+HP)=29;
HDF+HP
HP for 2h first, HDF treatment for 8-12h
CVVH
Follow-up:28 days
①Compared to Pre-treatment, P<0.05;
Outcome: ②Compared to control group, P<0.05
• Inflammatory mediators
• Organ function
• APACHE-II score
HD+HP treatment better decreases APACHE-II
• 28-day survival rate score than CVVH treatment significantly.

Modern Journal of Integrated Traditional Chinese and Western Medicine 2017 Nov, 26(32)
HDF+HP VS CVVH for SA-AKI
Tab.3 Comparison of Urine Volume and Kidney Function Pre & Post Treatment

Group 7 days 14 days


Indicator Pre-treatment post treatment post treatment

Scr HDF+HP
( μmol /L)
CVVH

BUN HDF+HP
( mmol /L) CVVH
Better improved kidney
HDF+HP
Urine NAG function in HD+HP group
(IU/L) CVVH

Γ-GTP HDF+HP
(IU/L) CVVH

HDF+HP
A1-MG
(mg/L) CVVH

HDF+HP
Urine Volume
(mL/d) CVVH

①Compared to Pre-treatment, P<0.05;


②Compared to control group, P<(0.05) Group

Modern Journal of Integrated Traditional Chinese and Western Medicine 2017 Nov, 26(32)
HDF+HP VS CVVH for SA-AKI

Tab.4 Changes of Inflammatory Cytokines Pre and Post treatment

Group Time

Pre-
treatment
HDF+HP Post-
treatment

Pre-
treatment
CVVH
Post-
treatment

①Compared to Pre-treatment, P<0.05; ②Compared to control group, P<0.05

Efficient removal of inflammatory mediators


Improve patients’ inflammatory status

Modern Journal of Integrated Traditional Chinese and Western Medicine 2017 Nov, 26(32)
HDF+HP VS CVVH for SA-AKI
28-day survival
70 65.5%
60
50
37.9%
40 Better 28-day survival rate shows in
30 HDF+HP group with significant difference.
20
10
0
CVVH HDF+HP (P<0.05)

Conclusion:
HDF + HP for the patients with sepsis induced AKI can
• effectively prevent further deterioration of renal function
• promote renal function recovery
• effectively remove inflammatory factors and improve inflammation in the body.
The combination of HDF+HP is safe which can be used as an alternative treatment
for patients with sepsis induced AKI.
Further study with larger samples and long-term observation is expected.

Modern Journal of Integrated Traditional Chinese and Western Medicine 2017 Nov, 26(32)
Summary

 Reduce inflammatory mediators

 Control cytokine storm

 Stabilize hemodynamic

 Avoid further organ damage

HA330 for  Benefit patients’ recovery


Critical Diseases
AKI to ESRD

BMJ 2019;364:k4891
HD/HDF+HP for ESRD
Comprehensive removal of uremic toxins

Small Uremic Toxin

HD/HDF Part Middle Uremic Toxin


+
HP Middle Uremic Toxin
Ideal combination
Protein-bound Uremic Toxin
Jafron Product Family

 18 years clinical experience


 More than 2 million cases annually
 Over 4000 hospitals’ clinical use
 Widely applied in over 30 countries
THANK YOU!

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