Transkript

1 Metabolische Konsequenzen der Hämodialysetherapie Prof. Dr. Wilfred Druml Klinik für Innere Medizin III; Abteilung für Nephrologie und Hämodialyse Medizinische Universität Wien/Allgemeines Krankenhaus Wien, Österreich

2 Metabolische Konsequenzen der Hämodialysetherapie Beteiligte Ursachen Verlust von Nährstoffen Verlust von Proteinen / Blut Inflammation durch Bioinkompatibilität Inflammation durch intestinale Effekte Effekte durch Antikoagulation gesteigerter Katabolismus erhöhte ROS-Produktion Beachte: diese Ursachen sind miteinander verflochten

3 Nährstoffverluste durch RRT Glukose / Wärme Aminosäuren (z.b. Glutamin) Peptide Albumin / Protein Wasserlösliche Vitamine Spurenelemente?? Elektrolyte (Phosphat!!) Carnitin etc... Beachte : Diese Verluste müssen in der Ernährung des HD- Patienten berücksichtigt werden!

4 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: Dialytic losses of vitamin C (n=19). Blood samples were collected before and after HDF session

5 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: 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).

6 Serum concentrations and clearances of folic acid and pyridoxal-5- phosphate during venovenous CRRT Fortin MC et al. Intensive Care Med 1999; 25: Daily removal of folic acid (in nmol/day) during CRRT as measured from the effluent side

7 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

8 Antioxidant status in patients on chronic hemodialysis therapy: impact of parenteral selenium supplementation König JS et al. Wien Klin Wochenschr 1997; 109: Selenium concentrations at blood inlet and outlet of the dialyzer capillary and in dialysate during hemodialysis in 7 patients

9 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: Mean serum phosphate during IHD in critically patients without or with sodium phosphate supplementation (hospital and 1- year mortality higher without supplementation 0.05)

10 Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation Ikizler A et al. Am J Physiol 2002; 282: E Net forearm muscle protein loss comparing predialysis and dialysis periods for individual data points

11 Inflammatory signals associated with hemodialysis Caglar Kaiser et al. Kidney int 2002; 62: Increment in fibrinogen fractional synthetic rates (FSR) during each study period * P< 0.05 vs. baseline

12 Inflammatory signals associated with hemodialysis Caglar Kaiser et al. Kidney int 2002; 62: 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

13 Skeletal muscle, cytokines, and oxidative stress in end-stage renal disease Raj DS et al. Kidney int 2005; 68: 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)

14 Activity of glutathione peroxidase in CO, CRF and HD patients Mimic-Oka J. et al. Clin. Nephrol. 51: , 1999 Glutathione peroxidase (U/L plasma) ** *** > < 20 HD Creatinine clearance (ml/min) ** p < 0.01 *** p < a p < 0.05 *** ***, a

15 Effect of a single hemodialysis session on inflammatory markers Bitla AR et al. Hemodial Int 2010; 14: 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

16 CVVH in Polytrauma Marzi I et al. Homburg/ Saar 1994 C-reactive protein in control group (o) and CVVH group

17 Splanchnic perfusion during hemodialysis: Evidence for marginal tissue perfusion Jakob SM et al. Crit Care Med 2001; 29: 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

18 Mucosal Biofilm in Congestive Heart Failure Low colonised large intestinal mucosa Highly colonised large intestinal mucosa Controls Chronic heart failure Bauditz & Swidsinski et al., DDW 2006, Poster # M1168

19 Circulating Endotoxemia: A Novel Factor in Systemic Inflammation and Cardiovascular Disease in Chronic Kidney Disease McIntyre CW et al. Clin-JASN 2011;6: (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

20 Associations between renal function, volume status and endotoxaemia in chronic kidney disease patients Goncalves S et al. NDT 2006; 21: 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%

21 Altered intestinal function in patients with chronic heart failure Sandek A. et al. J Am Coll Cardiol 2007; 50: 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)

22 The mortality risk of overhydration in haemodialysis patients Wizemann V et al. NDT 2009; 24: Kaplan Meier curve separating the patients for the relative hydration status (ΔHS >15%)

23 High dietary fiber intake is associated with decreased inflammation and allcause mortality in patients with chronic kidney disease Krishnamurthy VM. et al. Kidney int 2012; 81: 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

24 IL-1ß Receptor Antagonist Reduces Inflammation in Hemodialysis Patients Hung AM et al. JASN 2011; 22: 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

25 The Dark Side of Hemodialysis Ursachen der Endotoxinämie Dialysat Shunt Katheter! Oral health Volumenüberladung (Darm) repetitive intestinale Ischämie? Beachte : Eine (chronische) Endotoxinämie ist eine wichtige Ursach der Inflammation bei HD Patienten

26 Inflammation Dialyse-assoziierte Ursachen Bioinkompatibilität von künstlichen Membranen Bioinkompatibilität vom Schlauchsystem/ Luft-Blut Interaktion Inadäquate Dialysedosis (Urämie als Inflammation) Endotoxinämie Katheter-/ Shunt-Infektionen Verlust von antioxidativen Faktoren Interkurrente Infektionen Eisentherapie Antikoagulation (Heparin!) etc.

27 Hemodialysis stimulates muscle and whole body protein loss and alters substrate oxidation Ikizler 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)

28 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

29 Intradialytic Oral Nutrition Improves Protein Homeostasis in Chronic Hemodialysis Patients with Deranged Nutritional Status Pupim L et al JASN 2006; 17: Whole body (WB) protein homeostasis during HD, comparing control, IDPN and PO. * p< 0.05 vs. Control, p < 0.05 vs IDPN

30 Antikoagulation bei RRT Heparin nicht-antikoagulatorische Effekte Heparin AT-III -Verbrauch Zell-Aktivierung (Thrombocyten, Granulocyten) Heparin-induzierte Thrombopenie I + II ROS Bildung pro-inflammatorische Effekte metabolische Nebenwirkungen (Lipolyse) Allergische Reaktionen (Osteoporose) (Alopezie) LMWH haben etwas weniger ausgeprägte Effekte...

31 Antikoagulation bei CRRT Heparin 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, lipopolysaccharidebinding protein; M, monocyte; MPO, myeloperoxidase; SOD, superoxide dismutase; GAGs, glucosaminoglycans; P, platelet; L, leukocyte from Oudemans-van Straaten H, Crit Care 2011; 15: 202

32 Platelet activation in clinical haemodialysis: LMWH as a major contributor to bio-incompatibility? Gritters M et al. Nephrol Dia Transplant 2008; 23: 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 = vs baseline

33 Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation: dissociation of complement activation and neutropenia from neutrophil degranulation Böhler Joachim et al. J Am Soc Nephrol 1996; 7:

34 Effect of Hemodialysis Before Transplant Surgery on Renal Allograft Function A Pair of RCTs Kikic et al. Transplantation 2009;88: P= vs. 47 ml/min, p < 0.03 A A egfr ( ml/min) S A A S A A S S S A A A S S A A A A A A A Days after transplantation 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).

35 Danke für Ihre Aufmerksamkeit Prof. Dr. Wilfred Druml Klinik für Innere Medizin III; Abteilung für Nephrologie und Hämodialyse Medizinische Universität Wien/Allgemeines Krankenhaus Wien, Österreich