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Metabolische Konsequenzen der Hämodialysetherapie
Prof. Dr. Wilfred DrumlKlinik für Innere Medizin III;
Abteilung für Nephrologie und HämodialyseMedizinische Universität Wien/Allgemeines Krankenhaus Wien,
Österreich
l Verlust von Nährstoffenl Verlust von Proteinen / Blutl Inflammation durch Bioinkompatibilitätl Inflammation durch intestinale Effektel Effekte durch Antikoagulation l gesteigerter Katabolismus l erhöhte ROS-Produktion
Beachte: diese Ursachen sind miteinander verflochten
Beteiligte Ursachen
Metabolische Konsequenzen der Hämodialysetherapie
Nährstoffverluste durch RRT
l Glukose / Wärme…l Aminosäuren (z.B. Glutamin)l Peptide l Albumin / Proteinl Wasserlösliche Vitamine l Spurenelemente ?? l Elektrolyte (Phosphat!!)l Carnitin l etc ....
Beachte : Diese Verluste müssen in der Ernährung des HD-
Patienten berücksichtigt werden!
Convective and diffusive losses of vitamin C during hemodiafiltration
session: a contributive factor to oxidative stress in HD patients
Morena M. et al. Nephrol Dial Transplant 2002; 17: 422-27
Dialytic losses of vitamin C (n=19). Blood samples were collected before and after HDF session
Convective and diffusive losses of vitamin C during hemodiafiltration session:
a contributive factor to oxidative stress in hemodialysis patients
Morena M. et al. Nephrol Dial Transplant 2002; 17: 422-27
Convective and diffusive losses of vit C during HDF session. At 60 min of HDF, vit C contents in AL, VL, D, and UF were assessed. A total loss of vit C could be assessed at 66 mg/session (8–230).
Serum concentrations and clearances of folic acid and pyridoxal-5-
phosphate during venovenous CRRTFortin MC et al. Intensive Care Med 1999; 25: 594-598
Daily removal of folic acid (in nmol/day) during CRRT as measured from the effluent side
Lactic Acidosis in Thiamine -Deficiency
Madl Christian et al. Clin Nutr 1993; 12: 67
Plasma lactate concentrations in two patients with thiamine deficiency before and after thiamine infusion
Antioxidant status in patients on chronic hemodialysis therapy: impact of parenteral
selenium supplementationKönig JS et al. Wien Klin Wochenschr 1997; 109: 13-19.
Selenium concentrations at blood inlet and outlet of the dialyzer capillary and in dialysate during hemodialysis in 7 patients
Severe acute hypophosphatemia during renal replacement therapy (IHD)
adversely affects outcome of critically ill patientswith acute kidney injury
Schiffl H. et al. Int Urol Nephrol 2013; 45: 191-97
Mean serum phosphate during IHD in critically patients without or with sodium phosphate supplementation (hospital and 1-
year mortality higher without supplementation 0.05)
Hemodialysis stimulates muscle and whole body protein loss and alters
substrate oxidationIkizler A et al. Am J Physiol 2002; 282: E107-16
Net forearm muscle protein loss comparing predialysis and dialysis periods for individual data points
Inflammatory signals associated with hemodialysis
Caglar Kaiser et al. Kidney int 2002; 62: 1408-16
Increment in fibrinogen fractional synthetic rates (FSR) during each study period * P< 0.05 vs. baseline
Inflammatory signals associated with hemodialysis
Caglar Kaiser et al. Kidney int 2002; 62: 1408-16
Increment in IL-6 concentration during each study period for each individual patient. The mean depicted in bold.
*significant from baseline period (P < 0.05); denotes P = 0.05 vs. hemodialysis for mean
Skeletal muscle, cytokines, and oxidative stress in end-stage renal
diseaseRaj DS et al. Kidney int 2005; 68: 2338-43
Interleukin-6 (IL-6) and hemeoxygenase-1 (HO-1) and suppressors of cytokine signaling-2 (SOCS-2) gene expression in skeletal muscle (!) were increased during hemodialysis (HD)
Activity of glutathione peroxidase in CO, CRF and HD patients
Mimic-Oka J. et al. Clin. Nephrol. 51:233-241, 1999G
luta
thio
ne p
erox
idas
e (U
/L p
lasm
a)
> 90 51-90 21-50 < 20 HDCreatinine clearance (ml/min)
0
100
200
300
400
*****
*** ***, a
** p < 0.01*** p < 0.001
a p < 0.05
Effect of a single hemodialysis session on inflammatory markers
Bitla AR et al. Hemodial Int 2010; 14: 411-17
Time course of changes observed in LpPLA2 activity. Data were corrected for hemoconcentration with albumin converted to percentages (predialytic value =100%). LpPLA2 lipoprotein
associated phospholipase A2
CVVH in PolytraumaMarzi I et al. Homburg/ Saar 1994
C-reactive protein in control group (o) and CVVH group
Splanchnic perfusion during hemodialysis: Evidence for marginal
tissue perfusionJakob SM et al. Crit Care Med 2001; 29: 1393-98
Fractional splanchnic blood flow before, during, after hemodialysis. The 20%, 30%, and 40% lines = proportion of splanchnic blood flow of cardiac index and fractional femoral blood flow before, during, and after hemodialysis. The 4%, 8%, and 12% lines =
proportion of femoral blood flow of cardiac index
Mucosal Biofilm in Congestive Heart Failure
Highly colonised large intestinal mucosa
Low colonisedlarge intestinal mucosa
Controls Chronic heart failure
Bauditz & Swidsinski et al., DDW 2006, Poster # M1168
Circulating Endotoxemia: A Novel Factor in Systemic Inflammation and Cardiovascular
Disease in Chronic Kidney DiseaseMcIntyre CW et al. Clin-JASN 2011;6:133-41
(a) Distribution of circulating endotoxin levels across the spectrum of CKD patients at baseline. Pediatric HD patients are
illustrated separately (OE). (b) Association of estimated GFR and circulating endotoxin levels in nondialysis-dependent CKD patients
Associations between renal function, volume status and endotoxaemia in
chronic kidney disease patientsGoncalves S et al. NDT 2006; 21: 2788-94
Correlation between endotoxin levels and fluid status in patients with CKD 3 - 4 (GFR 34 ml/min).
*Fluid overload defined as inferior vena cava diameter of >11.5mm/m2 **defined as collapsing index <40%
Sandek A. et al. J Am Coll Cardiol 2007; 50: 1561-6
Bowel wall thickness (transcutaneous abdominal sonography) of terminal ileum, ascending colon, transverse colon, descending colon and sigmoid in
chronic heart failure (CHF) patients compared with control subjects. Measurement of bowel wall thickness in a healthy control subject (B) and a
patient with CHF (C)
Altered intestinal function in patients with chronic heart failure
The mortality risk of overhydration in haemodialysis patients
Wizemann V et al. NDT 2009; 24: 1574-79
Kaplan–Meier curve separating the patients for the relative hydration status (ΔHS >15%)
High dietary fiber intake is associated with decreased inflammation and all-
cause mortality in patients with chronic kidney disease
Krishnamurthy VM. et al. Kidney int 2012; 81: 300-06
Associations of dietary fiber with elevated serum C-reactive protein(>3mg/l) in the non-chronic kidney disease (CKD) and CKD sub-populations. Model adjusted for many confounders
IL-1ß Receptor Antagonist Reduces Inflammation in Hemodialysis Patients
Hung AM et al. JASN 2011; 22: 437-42
Pre- and poststudy levels of hsCRP (mg/dl) and IL-6 (pg/ml). hsCRP decreased in all but one individual in with IL-1ra
(Anakinra), all placebo subjects were either stable or increased their hsCRP. A similar trend was observed for IL-6 levels
l Dialysatl Shuntl Katheter !l „Oral health“l Volumenüberladung (Darm) l repetitive intestinale Ischämiel ?
Beachte : Eine (chronische) Endotoxinämie ist eine wichtige Ursach der Inflammation bei HD Patienten
The Dark Side of Hemodialysis
Ursachen der Endotoxinämie
l Bioinkompatibilität von künstlichen Membranenl Bioinkompatibilität vom Schlauchsystem/
Luft-Blut Interaktion l Inadäquate Dialysedosis (Urämie als Inflammation)l Endotoxinämie l Katheter-/ Shunt-Infektionenl Verlust von antioxidativen Faktoren l Interkurrente Infektionenl Eisentherapiel Antikoagulation (Heparin !)l etc.
InflammationDialyse-assoziierte Ursachen
Hemodialysis stimulates muscle and whole body protein loss and alters
substrate oxidationIkizler AP et al. Am J Physiol 2002; 282: E107-E116
Whole body protein metabolism. FFM, fat-free mass. *Significant difference from basal period (P < 0.05); §significant difference
between dialysis and postdialysis periods (P < 0.05)
Protein intake during hemodialysis maintains a positive whole body protein balance in chronic hemodialysis patients
Veeneman JM. et al. Am J Physiol 2003; 284: E954
Whole body protein breakdown (gray bars), synthesis (open bars), and protein balance (filled bars) during HD and fasting (fas) and a test meal (fed)HD- between HD HD+ during HD
Intradialytic Oral Nutrition Improves Protein Homeostasis in Chronic
Hemodialysis Patients with Deranged Nutritional Status
Pupim L et al JASN 2006; 17: 3149-57
Whole body (WB) protein homeostasis during HD, comparing control, IDPN and PO. * p< 0.05 vs. Control, § p < 0.05 vs IDPN
Antikoagulation bei RRT
Heparinl AT-III - Verbrauchl Zell-Aktivierung (Thrombocyten, Granulocyten)l Heparin-induzierte Thrombopenie I + IIl ROS Bildungl pro-inflammatorische Effekte l metabolische Nebenwirkungen (Lipolyse)l Allergische Reaktionenl (Osteoporose)l (Alopezie)
Heparin – nicht-antikoagulatorische Effekte
LMWH haben etwas weniger ausgeprägte Effekte..….
Antikoagulation bei CRRTHeparin and Inflammation
Heparins bind to proteins and cells, and thereby interfere with the inflammatory cascade and, altogether, confer unpredictable consequences for critically ill patients. H, heparin; AT, antithrombin; LBP, lipopolysaccharide-binding protein; M, monocyte; MPO, myeloperoxidase; SOD, superoxide dismutase; GAGs, glucosaminoglycans; P, platelet; L, leukocyte
from Oudemans-van Straaten H, Crit Care 2011; 15: 202
Platelet activation in clinical haemodialysis: LMWH as a major
contributor to bio-incompatibility?Gritters M et al. Nephrol Dia Transplant 2008; 23: 2911-17
Platelet factor 4 (PF4) (IU/ml) during HD (t0, t5, t30, t60 and t150) at 3 sampling points in the ECC, (1) afferent line (before roller pump), (2) first deflation chamber (between roller pump and dialyser), (3) efferent line (after the dialyser)°P = 0.005 vs baseline
Reduction of granulocyte activation during hemodialysis with regional citrateanticoagulation: dissociation ofcomplement activation and neutropenia from neutrophil degranulation
Böhler Joachim et al.J Am Soc Nephrol 1996; 7: 234-41
Effect of Hemodialysis Before Transplant Surgery on Renal
Allograft Function—A Pair of RCTsKikic et al. Transplantation 2009;88:1372-85
Effect of pretransplant dialysis mode on glomerular filtration rate. (B) Comparison of preoperative dialysis with systemic heparin anticoagulation
(open plots) versus dialysis with citrate anticoagulation (hatched plots).
A
A
S
A
A
A
S
S
SS
S
AAA
AA
S
SSS
A
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AA
A
A AA
25
50
75
100
125eG
FR (
ml/m
in)
Days after transplantation
0.8 0.9 0.9 0.6 0.5 0.3 0.1P=0.3
1 2 3 4 5 6 7 30 365
0.0336 vs. 47 ml/min, p < 0.03
Danke für Ihre Aufmerksamkeit
Prof. Dr. Wilfred DrumlKlinik für Innere Medizin III;
Abteilung für Nephrologie und HämodialyseMedizinische Universität Wien/Allgemeines Krankenhaus Wien,
Österreich
