Substitution of citrate with tissue plasminogen activator (rt-PA) for catheter lock does not improve patency of tunnelled haemodialysis catheters in a randomised trial.

BACKROUND: The study aim was to establish if substitution of citrate with rt-PA for catheter lock once weekly can reduce the incidence of catheter-related blood stream infections (CR-BSI) or improve patency of tunneled haemodialysis catheters. METHODS: All incident patients undergoing insertion of a tunneled haemodialysis catheter were screened and included except those suffering infection or using oral anticoagulation. Study participants were randomized into two arms according to the solution applied as catheter lock: receiving either trisodium citrate (Citra-LockTM 4%) only or rt-PA (Actilyse® 1 mg/ml) on the middle session each week with citrate used on the first and third sessions. The incidence of CR-BSI (confirmed by positive blood culture), catheter non-function (complete obstruction), and malfunction (blood flow < 250 ml/min) was recorded. Statistical significance was tested with ANOVA, post hoc analysis was performed by means of multiple linear regression. RESULTS: Totally, 18 patients were included and followed during 655 haemodialysis sessions. No episode of CR-BSI was detected while 6 catheter non-functions (0.9% sessions) and 101 malfunctions (15.4% sessions) were recorded. The incidence of both events was equal between the study arms: 4 non-functions and 55 malfunctions in the rt-PA arm and 2 non-functions and 46 malfunctions in the citrate arm (p = 0.47 and p = 0.24, respectively). Additionally, the mean blood flow achieved did not differ significantly between the arms: 326 ± 1,8 and 326 ± 1,9 ml/min (p = 0.95) in rt-PA and citrate arms, respectively. Post hoc analysis identified time elapsed since previous session (ß = 0.12, p = 0.005) and malfunction on previous session (ß = 0.25, p < 0.001) as significant factors affecting the occurrence of malfunction. By contrast, the study arm, rt-PA application on previous session, and catheter vintage did not enter the model. CONCLUSION: Substitution of citrate with rt-PA for catheter lock does not reduce the incidence of catheter malfunction neither does it affect the blood flow achieved during haemodialysis. Catheter patency is related rather to the time interval between sessions and to previous malfunction (thus probably reflecting undefined individual factors). The incidence of CR-BSI within pre-selected haemodialysis population is sporadic (less than 1 per 4.3 patient years in our sample). TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12612000152820 . Retrospectively registered 03/02/2012.

Citrate-Buffered Dialysis Solution (Citrasate) Allows Avoidance of Anticoagulation During Intermittent Hemodiafiltration-At the Cost of Decreased Performance and Systemic Biocompatibility.

Reportedly, citrate-based dialysis solution enables heparin dose tapering or even complete exclusion, particularly in postdilution hemodiafiltration (HDF). The aim of the study was to verify this strategy in predilution setting and to assess its short-term safety, efficacy, and biocompatibility. Ten regular hemodialysis patients were assigned to predilution HDF on acetate- and citrate-based dialysis solutions (0.8 mmol/l trisodium citrate) at random order. Acetate HDF was performed using routine dose of heparin while citrate HDF was heparin free. Plasma calcium, thrombin-antithrombin complexes (TAT), and citrate levels were measured at 0, 30, 60, 120, and 240 min. Following each session, a semiquantitative dialyzer clotting score (DCT 1-5) was assessed and HDF adequacy was determined as spKt/V. Statistical relevance was tested by ANOVA with pP < 0.05 held significant, data are given as means ± standard deviations. All sessions were accomplished successfully, premature termination or circuit re-setting was not necessary. However, DCT was significantly higher in citrate-HDF compared to acetate-HDF regimen (3.4 ± 0.65 and 1.8 ± 0.79, respectively, P = 0.002) as well as TAT generation rate (increase per session by factor 11.0 ± 8.43 and 2.1 ± 1.26, respectively, P = 0.004 between regimens). Ionized calcium declined only by the end of citrate-HDF (from 1.09 ± 0.086 to 0.99 ± 0.030 mmol/L, P = 0.002) yet without accompanying clinical symptoms. Systemic citrate levels increased along the citrate-HDF session but stayed an order of magnitude below concentrations needed to establish citrate anticoagulation (peak at 0.276 ± 0.112 mmol/L). Dialysis adequacy estimated by spKt/V was found lower in citrate-HDF vs. acetate-HDF (1.48 ± 0.163 and 1.58 ± 0.165, respectively, P = 0.006). Although predilution HDF using citrate-based dialysate is feasible without heparin, both dialysis adequacy and biocompatibility is significantly compromised. Therefore, this approach can be adopted for a single procedure but is not acceptable on a regular basis.

Evaluation of three different methods to prevent dialyzer clotting without causing systemic anticoagulation effect.

Thrombogenicity is one of the most important biocompatibility markers of artificial material. Anticoagulation is commonly used to reduce thrombogenicity of the extracorporeal circuit (ECC) during intermittent hemodialysis (IHD). In some situations, systemic anticoagulants are contraindicated. The aim of our study was to compare thrombogenicity parameters during IHD with three different methods without a systemic anticoagulation effect. In a prospective, randomized, and crossover study, we examined 10 stable patients during IHD with (i) regular saline flushes of ECC; (ii) regional citrate anticoagulation (RCA); and (iii) AN69 ST membrane after ECC priming according to the manufacturer's recommendations. Before IHD and after 10, 60, 120, and 240 min, we measured the platelet count and the plasma concentrations of platelet factor 4 (PF4) and thrombin/antithrombin complexes (TAT). All 10 procedures with RCA were successfully completed after 4 h, whereas 6/10 procedures with saline flushes and 5/10 procedures with AN69 ST were finished prematurely because of clotting (P < 0.05). The TAT production was significantly increased during saline flushes and AN69 ST compared with RCA (P < 0.05). Platelet activation demonstrated by rising PF4 was present during all three methods. Markers of coagulation cascade activation were progressively increasing during IHD with RCA, saline flushes, and AN69 ST. The activation was significantly lower during RCA, and according to thrombogenicity, RCA is the most effective among compared anticoagulation methods.

Proteomic profiling of blood-dialyzer interactome reveals involvement of lectin complement pathway in hemodialysis-induced inflammatory response.

PURPOSE: dialysis-induced inflammatory response including leukocyte and complement activation is considered a significant cofactor of chronic morbidity in long-term hemodialysis (HD) patients. The aim of this study was to provide better insight into its molecular background. EXPERIMENTAL DESIGN: in 16 patients, basic biocompatibility markers, i.e. leukocyte counts and C5a levels, were monitored during HD on a polysulfone membrane. Proteins adsorbed to dialyzers were eluted and separated by 2-DE. Selected proteins were identified by MS; ficolin-2 plasma levels were assessed. Data are given as medians (quartile ranges). RESULTS: in total, 7.2 (34.7) mg proteins were retrieved from dialyzer eluates and were resolved into 217 protein spots. The proteins most enriched in eluates (and hence selectively adsorbed) were those involved in complement activation (C3c, ficolin-2, mannan-binding lectin serine proteases, properdin) and cell adhesion (actin, caldesmon, tropomyosin, vitronectin, vinculin). A significant decrease of plasma ficolin-2 (41% [4.7], p<0.001) was evidenced during one HD session, associated with leukopenia (r=0.73, p=0.001) and C5a production (r=-0.62, p=0.01) at 15 min. CONCLUSIONS AND CLINICAL RELEVANCE: ficolin-2 adsorption to polysulfone dialyzer initiates the lectin pathway of complement activation, mediates dialysis-induced leukopenia, and results in a significant depletion of ficolin-2, an essential component of innate immunity.

The AN69 ST haemodialysis membrane under conditions of two different extracorporeal circuit rinse protocols a comparison of thrombogenicity parameters.

BACKGROUND: Thrombogenicity is an important parameter of haemodialysis (HD) membrane biocompatibility. The surface of the polyacrylonitrile AN69 ST membrane is coated with a polyethylenimine. This modification allows heparin adsorption. The binding of heparin to the membrane surface occurs during priming of the extracorporeal circuit (ECC) by rinsing it with saline and heparin. Our aims were to assess and compare the thrombogenicity of the AN69 ST membrane under conditions of two extracorporeal circuit (ECC) rinse protocols-with and without unfractionated heparin (UFH). METHODS: In a prospective, crossover and randomized study, we examined 10 patients during HD after ECC preparation with either rinse protocols. Prior to HD and at 15, 60 and 240 min, we determined plasma levels of the thrombin-antithrombin complexes (TAT), platelet factor 4 (PF4), heparin concentration (antiXa) and thrombocyte count. Systemic anticoagulation was performed using UFH. RESULTS: During HD after ECC rinse without UFH, there was a significantly earlier and more marked increase in TAT compared with UFH-containing rinse (P <0.05). Using Spearman coefficient, we demonstrated a significant correlation between TAT and antiXa at 60 min (r = -0.534) and 240 min (r = -0.538). A comparison of the TAT/antiXa ratios between rinses at 60 min revealed a significantly higher increase in TAT following UFH-free rinse (P <0.05). There was no difference in PF4 between the rinses. Platelet count did not change significantly during HD using either rinse protocol. CONCLUSION: Based on plasma TAT levels, ECC priming with an UFH-containing solution reduces the thrombogenicity of the AN69 ST membrane. There is no significant difference between both types of priming concerning PF4 and thrombocyte count.

Citrate anticoagulation control by ionized calcium levels does not prevent hemostasis and complement activation during hemodialysis.

The purpose of this study was to determine whether or not regional citrate anticoagulation (RCA) controlled by ionized calcium (iCa(2+)) would overcome thrombogenicity, prevent hemostasis, and complement activation during hemodialysis (HD). RCA was performed in 10 patients during 10 HD sessions using a polysulfone membrane in an effort to keep iCa(2+) at dialyzer outlet at < or =0.4 mmol/L. Compared to baseline, plasma levels of thrombin-antithrombin III complexes rose significantly at 240 min, and tissue factor and complement C5a component levels at 30 and 240 min of the procedure. Thrombocyte count declined significantly at 30 and 240 min, while activated clotting time (ACT) did not increase significantly, and platelet factor 4 as well as von Willebrand factor levels did not alter significantly. While ACT correlated significantly with some thrombogenicity markers, iCa(2+) did not correlate with ACT, changes in hemostasis, or C5a. We conclude the usually recommended iCa(2+) levels in the HD extracorporeal circuit did not guarantee the complete overcoming of thrombogenicity, prevention of hemostasis, and complement activation.