UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS
Transcript of UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS
![Page 1: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/1.jpg)
UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS
EVELIEN SNAUWAERT, MD, PhD
DEPARTMENT OF PEDIATRIC NEPHROLOGYGhent University Hospital, Belgium
![Page 2: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/2.jpg)
Uremic toxins, introduction
![Page 3: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/3.jpg)
Introduction
Homeostasis of fluid, electrolytes & acid-base
Water-soluble
Protein-bound
Middle molecule
Waste product removalEndocrine function
“Uremic toxins”
![Page 4: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/4.jpg)
Introduction
Water-soluble
Protein-bound
MW < 500 Da
Diffusion
Concentration gradient
Urea
MW > 500 Da
Convection
Pressure gradient
Β2-microglobulin
< 500 Da, protein-bound
Difficult to remove
Indoxyl sulfate, p-cresylsulfate
Middle molecule
![Page 5: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/5.jpg)
OXIDATIVE STRESS
β2M
ADMA
INFLAMMATION
FIBROSIS
CARDIOVASCULAR DISEASE
METABOLIC DISEASE
INFECTION
pCS
IxS
HA
Pathophysiology
![Page 6: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/6.jpg)
Which uremic toxins are making our patient sick?
Confounding factors (pre-existing CV disease)
Large inter-patient variability
Inability to decrease a single compound
Complex and multifactorial interplay between different key elements, present for longer time
![Page 7: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/7.jpg)
Which uremic toxins are making our patient sick?
No confounding factors or co-morbidities
Isolated kidney disease
Growth
Opportunities in pediatric population
![Page 8: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/8.jpg)
Enhancing uremic solute removal improves growth
![Page 9: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/9.jpg)
In pediatrics?
![Page 10: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/10.jpg)
UToPaed study: uremic toxins in pediatric CKD
more advanced and appropriate tools to improve management of children
with CKD
![Page 11: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/11.jpg)
Uremic toxins, how to clear them?
![Page 12: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/12.jpg)
PLASMA
How to clear uremic toxins?
SOLUTE REMOVAL IN THE DIALYZER
1
SOLUTE TRANSPORT IN THE PATIENT
2
Clearance & extraction ratio
KineticsTotal solute removal (mass)
![Page 13: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/13.jpg)
DIALYZER
Solute transport in the dialyzer
Clearance and extraction ratio ≈ blood flow + membrane + dialysate flow
Adding convection to diffusion
Dialyzer fiber length, diameter and permeability
Eloot et al., Comp Meth Biomech Biomed Eng 2006; Leypoldt et al., Kidney Int, 1999
![Page 14: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/14.jpg)
DIALYZER
Solute transport in the dialyzer
Diffusion = well established removal strategy of free fraction protein-bound uremic toxins
Meyer et al., Seminars in dialysis 2011; Sirich et al., NDT, 2012; Meert et al., NDT, 2009
TACurea decreases by 15% TACsolute decreases by 50%
Larger membrane & higher Qd
![Page 15: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/15.jpg)
Solute transport in the dialyzer
Dialysate Blood Dialysate Blood Dialysate Blood
Post-HDF High flux HD Low flux HD
37 42 18
Research question: does post-HDF decrease levels of protein-bound uremic toxins ?
baseline
12 months
Snauwaert et al., NDT, 2020 Apr 1;35(4):648-656.
DIALYZER
![Page 16: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/16.jpg)
µg
/mL
mg
/dL
PROTEIN-BOUND UREMIC TOXINSMIDDLE MOLECULES
Snauwaert et al., NDT, 2020 Apr 1;35(4):648-656.
Solute transport at the dialyzer
DIALYZER
![Page 17: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/17.jpg)
PLASMATIC COMPARTMENT
SOLUTE TRANSPORT IN THE PATIENT
Solute transport in the patient
Generation (G)
Renal (Krenal)
Dialyzer (Kdialyer)
Inter-compartmentalclearance (K12)
OTHER DEEPER TISSUES
BLOOD CELLS, ALBUMIN
Eloot et al., Seminars in Dialysis, 2012
![Page 18: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/18.jpg)
PLASMA
PATIENT
Solute transport in the patient
Eloot et al., Seminars in Dialysis, 2012; Eloot et al., PLOS one, 2016
Two-compartiment kinetic model
Removal will be limited for solutes with- Large distribution volume - Slow intercompartimental clearance (K12)
![Page 19: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/19.jpg)
PLASMA
PATIENT
Solute transport in the patient
Eloot et al., PLOS one, 2016
Slow intercompartimentalclearance (K12)
= slow transport into the plasma
. β2M
![Page 20: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/20.jpg)
PLASMA
PATIENT
Solute transport in the patient
Eloot et al., Kidney International, 2008
Patient needs time to mobilizeuremic toxins into the plasma
![Page 21: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/21.jpg)
PLASMA
PATIENT
Solute transport in the patient
Eloot et al., PLOS one, 2016
Dialyzer clearance shows an inverse relationwith % protein-binding
![Page 22: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/22.jpg)
![Page 23: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/23.jpg)
![Page 24: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/24.jpg)
Current markers are poor predictors of overall uremic toxinaccumulation
pCS
IxS
HA
β2M
ADMA
ureaeGFRKt/V
Cystatin C
creatinine
Snauwaert et al. 2018 (Ped Nephrol)
![Page 25: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/25.jpg)
Eloot et al., Kidney Int, 2016; Fischbach et al., 2009
Alternative strategies to decrease uremic toxicity?
time…
Extended hemodialysis
strategies
![Page 26: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/26.jpg)
Alternative strategies to decrease uremic toxicity?
MEMBRANES WITH ADSORPTIVE CAPACITY
PRESERVATION OF RESIDUAL KIDNEY FUNCTION
Jansens et al. 2016; Tijink et al. 2014
DIETARY FIBER, PRE-, PRO, andSYNBIOTICS
![Page 27: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/27.jpg)
Conclusion and take-home message
With even the most recent advances, it seems thatsmall solute removal in the dialyzer is close to itsoptimum.
eGFR and Kt/V are poor predictor of overall uremictoxin accumulation and removal
Solute transport in the patient limits the increase of performance with the traditional dialytic approaches.
![Page 28: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/28.jpg)
TEAMWORK DIVIDES THE TASK & DOUBLE THE SUCCESS
Mentors & Promotors Sunny ElootJohan Vande WalleWim Van BiesenAnn RaesGriet GlorieuxRaymond VanholderRukshana Shroff
Lab & dataSophie LobbestaelTom MertensMaria VanlandschootSofie VermeirenEls HolvoetSanne Roels An DesloovereElke De Bruyne
All patients andfamilies participating
CollaboratorsElena LevtchenkoNathalie GodefroidKoen Van HoeckLaure CollardChiodini BenedettaRukshana Shroff
& their local team
Charlotte VanherzeeleChristel BeerensNathalie PolflietKatty Van CauwenbergheKatya DegrooteKarlien Dhondt Members of advisory board
![Page 29: UREMIC TOXINS: HOW TO CLEAR THEM DURING HEMODIALYSIS](https://reader034.fdocuments.net/reader034/viewer/2022042718/626755e7cf524a125d449350/html5/thumbnails/29.jpg)
THANK YOU!Evelien Snauwaert, MD, PhD
Pediatric Nephrologist
Department of Pediatric NephrohlogyGhent University Hospital, Belgium
[email protected]+32 9 332 69 05
www.uzgent.be