Activation of the kallikrein-kinin system in hemodialysis: Role of membrane electronegativity, blood dilution, and pH

Renaux, Jean-Louis; Thomas, M; Crost, T.; Loughraieb, Nathalie; Vantard, Georges

doi:10.1046/j.1523-1755.1999.0550031097.x

Cited by 83 publications

(60 citation statements)

References 14 publications

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“…ACE inhibition enhances bradykinin effects by decreasing its breakdown, whereas ARB does not. In addition, hemodialysis increases bradykinin levels, 28 albeit to lesser extent with polysulfone membranes than polyacrylonitrile membranes. Supporting a proinflammatory role of bradykinin is the observation that bradykinin B 2 -receptor blockade increases circulating IL-10 in an animal model of ischemia/reperfusion.…”

Section: Discussionmentioning

confidence: 94%

“…[24][25][26][27] Hemodialysis also stimulates activation of the kallikrein-kinin system and the production of bradykinin. 28 Endogenous bradykinin contributes to increases in PAI-1 and monocyte chemoattractant protein-1 after hemodialysis. 29 Thus, any intervention that increases bradykinin, such as ACE inhibitors, may increase the inflammatory response to hemodialysis in MHD patients.…”

mentioning

confidence: 99%

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Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Gamboa¹,

Pretorius²,

Todd-Tzanetos³

et al. 2012

Journal of the American Society of Nephrology

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Biomarkers of oxidative stress and inflammation predict cardiovascular events in maintenance hemodialysis patients. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) reduce cardiovascular mortality in the general population, but their benefit in maintenance hemodialysis patients is not fully explored. To test whether ACE inhibitors and ARBs differentially affect markers of oxidative stress, inflammation, and fibrinolysis during hemodialysis, we conducted a randomized, doubleblind, placebo-controlled 333 crossover study. We randomly assigned 15 participants undergoing hemodialysis to placebo, ramipril (5 mg/d), and valsartan (160 mg/d) for 7 days, with a washout period of 3 weeks in between the treatments. On the morning of the seventh day of drug treatment, participants underwent serial blood sampling during hemodialysis. Neither ramipril nor valsartan affected BP during hemodialysis. Ramipril increased IL-1b concentrations (P=0.02) and decreased IL-10 concentrations (P=0.04) compared with placebo. Valsartan and ramipril both lowered IL-6 levels during dialysis (P,0.01 for each compared with placebo). Valsartan increased F 2 -isoprostane levels, and ramipril suggested a similar trend (P=0.09). Valsartan and ramipril both lowered D-dimer levels (P,0.01 for both), whereas only ramipril seemed to prevent a rise in vWf levels (P=0.04). In summary, during hemodialysis, valsartan induces a greater anti-inflammatory effect compared with ramipril, although ramipril seems to prevent dialysis-induced endothelial dysfunction as measured by levels of vWf. A prospective clinical trial is necessary to determine whether ACE inhibitors and ARBs also differ with respect to their effects on cardiovascular mortality in this population. 23: 334-342, 201223: 334-342, . doi: 10.1681 In ESRD patients, cardiovascular death accounts for .50% of overall mortality and the risk of cardiovascular death is 30 times higher than in the general population. 1,2 Moreover, patients undergoing maintenance hemodialysis (MHD) have a 5-year survival rate of 10% after acute myocardial infarction. 3 Traditional risk factors, as used in Framingham risk scoring, only explain half of the excessive cardiovascular mortality observed in ESRD patients, 4 and it is thought that other factors contribute to the high cardiovascular mortality among ESRD patients. J Am Soc NephrolIncreased oxidative stress and inflammation may contribute to accelerated atherosclerosis and cardiovascular events in patients with MHD. 5,6 Markers of oxidative stress, such as F 2 -isoprostanes, are increased in MHD patients. 7,8 Inflammatory markers, particularly IL-1, IL 6, and TNFa, are also elevated in MHD patients and are associated with

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Section: Discussionmentioning

confidence: 94%

mentioning

confidence: 99%

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Gamboa¹,

Pretorius²,

Todd-Tzanetos³

et al. 2012

Journal of the American Society of Nephrology

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“…This filter has been modified to avoid bradykinin release and has previously been reported safe for use in ACEI-treated patients [2,6,7]. This study demonstrates that such reactions may also appear with the AN69 ST filter.…”

Section: Discussionmentioning

confidence: 70%

“…The surface of the polyacrylonitrile membrane AN69 dialyzer is strongly electronegative, but pretreating the AN69 filter with polyethyleneimine reduces its surface electronegativity and allows heparin to bind more firmly [2,3,4]. An increased frequency of hypersensitivity reactions has previously been reported during HD with the electronegatively charged AN69 filter in patients treated with angiotensin-converting enzyme inhibitors (ACEI) [5].…”

Section: Introductionmentioning

confidence: 99%

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A Heparin-Coated Dialysis Filter (AN69 ST) Does Not Reduce Clotting during Hemodialysis when Compared to a Conventional Polysulfone Filter (F×8)

Sagedal

Witczak²,

Osnes³

et al. 2011

Blood Purif

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Background: We investigated whether the heparin-coated AN69 ST hemodialysis (HD) filter induced less hypercoagulability during HD than a conventional polysulfone filter (F×8). Methods: In a crossover design, 11 patients were treated alternately with AN69 ST and F×8 filters (45 sessions). All filters were primed with unfractionated heparin (UFH) and unadsorbed UFH was removed by saline flushing. Half the conventional dalteparin dose was given as a bolus dose at the start of HD. Clotting was evaluated hourly in the venous air trap. Prothrombin fragments 1 and 2 (PF1 + 2), antithrombin (AT), β-TG and anti-FXa activity were repeatedly measured. Results: One patient treated with enalapril had two repeated adverse reactions to the AN69 ST filter and was excluded from the study. Use of the AN69 ST filter did not decrease the mean clot score or PF1 + 2, but decreased β-TG compared to the F×8 filter. Conclusion: The heparin-coated AN69 ST filter did not induce less coagulation when compared to the F×8 filter.

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Hemodialysis

Ofsthun

2007

Kirk-Othmer Encyclopedia of Chemical Technology

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Hemodialysis is the most commonly‐employed process for cleaning the blood of a patient with kidney failure. In hemodialysis, blood flows on one side of a semipermeable membrane and dialysate solution flows on the other side of the membrane. Today, the typical artificial kidney, or dialyzer, consists of approximately ten thousand cylindrical polymer membranes (“hollow fibers”) through which blood flows. The hollow fibers contain pores which are large enough to let toxins pass, but small enough to retain plasma proteins. Dialysate, a solution containing physiological concentrations of several key solutes, flows around the hollow fibers in a counter‐current direction. Hemodialysis cleans the blood by a combination of diffusion, in which toxins move across the hollow fiber wall from high concentration (blood side) to low concentration (dialysate side), and convection, in which solutes are swept along with the fluid that moves through the membrane pores (from blood to dialysate) as a result of a pressure gradient. Small molecular weight waste products (<500 kDa) normally excreted in urine are transferred across the membrane primarily by diffusion, and flow down the drain with the dialysate. Excess water that accumulates between treatments is also removed, leading to convective removal of molecules in the so‐called “middle molecule” range of 500 to ∼15,000 Da. A typical hemodialysis regimen calls for three treatments per week, with each treatment lasting 3.5–4.0 hours. Approximately one million patients worldwide receive chronic hemodialysis today. In this article, the process of hemodialysis, design requirements for dialyzers, and properties of currently available hemodialysis membranes, introducing terminology peculiar to the dialysis industry that may be unfamiliar to scientists in other fields are reviewed.

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Activation of the kallikrein-kinin system in hemodialysis: Role of membrane electronegativity, blood dilution, and pH

Abstract: Our in vitro experimental approach evidences the importance of the control of these physicochemical factors to decrease the activation of the contact system.

Cited by 83 publications

References 14 publications

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

Comparative Effects of Angiotensin-Converting Enzyme Inhibition and Angiotensin-Receptor Blockade on Inflammation during Hemodialysis

A Heparin-Coated Dialysis Filter (AN69 ST) Does Not Reduce Clotting during Hemodialysis when Compared to a Conventional Polysulfone Filter (F×8)

Hemodialysis

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