Comparative analysis of procoagulatory activity of haemodialysis, haemofiltration and haemodiafiltration with a polysulfone membrane (APS) and with different modes of enoxaparin anticoagulation.

BACKGROUND: Treatment modalities of renal replacement therapy differ in their diffusive and convective mass transfer characteristics. It was the goal of this study to clarify whether an increase in convective mass transfer as performed with haemofiltration (HF) and haemodiafiltration (HDF) in comparison with high-flux haemodialysis (HD) is associated with an alteration in procoagulatory activity or with complement activation. METHODS: Ten stable chronic HD patients were monitored during 120 treatments in a randomized cross over design. A high-flux polysulfone dialyser (APS 900) was used for high-flux HD, pre-dilution HF and pre-dilution HDF. Constant flow of on-line substitution fluid for HF and HDF was 200 ml/min. The low molecular weight heparin (LMWH) enoxaparin was used for anticoagulation (i) as single bolus (50 IU/kg body weight, median 3700 IU) and (ii) as bolus of 1200 IU followed by a median continuous dose of 400 IU/h. Blood samples were collected before the LMWH bolus, after 10 min, 60 min, 120 min and at the end of treatment in venous and arterial blood lines to determine antiXa activity, thrombin-antithrombin-III complex (TAT), D-dimer and C5a generation. RESULTS: Net ultrafiltration did not significantly differ between HD, HF and HDF but total ultrafiltration in HF and HDF far exceeded total ultrafiltration in HD. With conditions of single bolus, or bolus and continuous anticoagulation with enoxaparin, after comparable treatment times (median duration 4.25 h), TAT and D-dimer generation at identical anti-Xa levels revealed significantly higher coagulation activity during HF and HDF, compared with high-flux HD as assessed by comparative area under the curve (AUC) analysis. Plasma concentration of C5a in venous bloodlines did not significantly differ during HD, HF and HDF. CONCLUSION: A higher convective mass transfer during HF and HDF, in comparison with high-flux HD caused by a greater total ultrafiltration volume was associated with increased procoagulatory activity in the extracorporeal circuit. Molecular markers assessing the activation of coagulation are appropriate to adjust the anticoagulation regime to high UF volumes in order to minimize bleeding risk and optimize patency of the extracorporeal circuit.     

Continuous arteriovenous haemodiafiltration: optimal therapy for acute renal failure in an intensive care setting?

We report the results of continuous arteriovenous haemodiafiltration (CAVHD) treatment in 12 critically ill intensive care patients with acute renal failure (eight males, four females - mean age 60.9 years - range 47 to 76) (APACHE II score 28.8, range 18–37). All patients were oligo-anuric or had a rising creatinine ( 100 JμM/L per day). Vascular access was obtained by Scribner shunt or wide-bore femoral arterial and venous cannulae. At the beginning of CAVHD therapy the mean plasma urea was 38 mM/L (SE 4.5, 95% confidence interval (CI) 25.1 to 75.6 mM/L) and the mean creatinine was 604 μM/L (SE 70, 95% CI 450–756 μM/L). After 72 hours of therapy, despite oligoanuria, urea concentration had fallen to a mean of 15.7 mM/L (SE 2.4, 95% CI 12.5–22.9 mM/L) and the creatinine concentration to 297 μM/L (SE 25, 95% CI 243–351 μM/L), respectively. The mean ultrafiltrate volume was 441 mL/hr (SE 33, 95%, range 50–1050 mL/hr). There were no complications related to the extracorporeal circuit, the filter, anticoagulant therapy, electrolyte status or changes in patients' haemodynamic state. Excellent biochemical control of azotaemia was uniformly achieved during CAVHD therapy. Five patients (41.6%) survived to be discharged from the Intensive Care Unit. CAVHD is a simple, safe and effective continuous renal replacement therapy. CAVHD offers technical advantages over alternative therapy while providing equivalent or better biochemical control of azotaemia and volume status in critically ill patients with acute renal failure.     

Endotoxin transfer through dialysis membranes: small- versus large-pore membranes.

In this in-vivo study, dialysate and serum endotoxin was evaluated before and after haemodialysis with small-pore (PS400) and large-pore (PS600) polysulphone dialysers, and before and after haemodiafiltration with the PS600 filter. The source of the endotoxin was the presence in dialysate of Pseudomonads at a concentration of 10(3)-10(4) CFU/ml. Endotoxin was measured by a modified chromogenic limulus amoebocyte lysate (LAL) assay. In spite of dialysate endotoxin concentrations greater than 100 pg/ml, no changes in pre- versus posttreatment LAL reactivity were observed in PS400 dialysis and PS600 haemodiafiltration. In contrast, PS600 haemodialysis was related to an increase in serum LAL reactivity from 1.3 +/- 1.5 to 3.8 +/- 2.0 pg/ml (n = 15, P less than 0.01), and five patients (33.3%) showed a post-dialysis value in excess of 5 pg/ml. Our data are consistent with the absence of in-vivo endotoxin transfer during haemodialysis with small-pore dialyser membranes, and during haemodiafiltration with membranes with larger pores. An increase in LAL reactivity during haemodialysis with membranes with larger pores is, however, present, presumably due to the occurrence of backdiffusion/filtration with that specific strategy.     

Calcium balance and intact PTH variations during haemodiafiltration

BACKGROUND.: Recent approaches to prevent and treat secondary hyperparathyroidismin dialysis patients include decreasing dialysate Ca contentfrom 1.75 to 1.5 mM or lower. We have recently observed thatby decreasing dialysate Ca to 1.25 mM a rise in intact parathormoneserum levels occurs despite adequately controlled predialysisCa and phosphate serum levels. In that study complementary treatmentwith high-dose 1(OH) vitamin D3 was required to suppress theparathormone. In the present study we aimed to assess the totalCa balance as well as the modifications in parathormone inducedby the dialysis session in order to understand the reasons forwhich the rise in parathormone was induced. METHODS.: Fourteen HD patients treated with haemodi-afiltration threetimes/week gave their informed consent for the study. They weredistributed in two groups with identical treatment but for thedialysate Ca content which was 1.5 and 1.25 mM respectivelyand for the amount of oral CaCO₃ received. Total and ionizedCa, phosphate, pH, and albumin as well as parathormone weremeasured in serum before and after dialysis and in the spentdialysate during two dialysis sessions. RESULTS.: Serum ionized Ca (normalized to pH 7.4) did not change during1.25 mM dialysate Ca and significantly increased with 1.5mM(P<0.001). The end-dialysis values being 1.25±0.02and 1.38±0.02 mM respectively. Total Ca significantlydecreased with 1.25mM dialysate Ca (P<0.04) and increasedwith 1.5mM (P<0.003), the end-dialysis values being 2.51±0.03and 2.75±0.04mM respectively. In the dialysate the differencein ionized Ca concentrations, fresh minus spent dialysate was–1.78±1.12 mmol/l (NS) and 4.26±1.47 mmol/l(P<0.02) respectively for 1.25 and 1.5 mM dialysate Ca. Thedifference in total Ca concentrations, fresh minus spent dialysatewas –0.1±0.01 mmol/l (P<0.005 and –0.002±0.01 mmol/l (NS) respectively. Phosphate removal was higherin 1.25 mM dialysate-Ca-treated patients (40.4±1.75 mmol/sessionversus 34±1.3 mmol/session respectively, P<0.015).The use of 1.25 mM dialysate Ca did not result in a change inserum parathormone, while the use of 1.5 mM resulted in a decreaseof 43±15% (P<0.02) in patients with marked hyperparathyroidism. CONCLUSIONS.: Our data remind us of the difficulty in assessing Ca balancesand identifies the phosphate content as one of the factors influencingthe amount of ionized Ca in the dialysate. Although the long-termparathormone increase we observed using 1.25 mM dialysate Camay well not be explained only by the acute intradialytic modifications,the negative Ca balance identified here (which was missed withthe analysis of ionized Ca alone), and the lack of parathormoneinhibition may participate in the relapse of hyperparathyroidism.     

Los altos volúmenes convectivos se asocian a la mejoría del perfil metabólico en los pacientes diabéticos en hemodiafiltración online

Background and objective

Online haemodiafiltration (OL-HDF) with high convective transport volumes improves patient survival in haemodialysis. Limiting the amount of convective volume has been proposed in patients with diabetes mellitus due to glucose load that is administered with replacement fluid. The objective of the study was to analyse the influence of substitution volume on the evolution of the metabolic profile and body composition of incident diabetic patients on OL-HDF.

连续性血液透析滤过对MODS犬肝肾IL-6和IL-10 mRNA表达的影响

目的：探讨连续性血液透析滤过（CVVHDF）后多器官功能障碍综合征（MODS）犬肝、肾组织白细胞介素-6（IL-6）和白细胞介素-10（IL-10）mRNA表达水平的变化及意义。方法：15只雄性Beagle犬,采用失血性休克＋复苏灌注＋内毒素血症复制MODS模型,随机分为CVVHDF组（n=8）和MODS组（n=7）,CVVHDF组在内毒素注射完毕后给予CVVHDF治疗12h,MODS组不给CVVHDF治疗。测定各器官功能相关指标,同时应用半定量逆转录-聚合酶链反应（RT-PCR）测定两组肝、肾组织中IL-6、IL-10mRNA表达水平。结果：CVVHDF组治疗后肝、肾功能有关指标水平均有不同程度的改善;与MODS组相比,在内毒素注射后3h及以后各时间点,血清肌酐（Scr）、尿素氮（BUN）水平显著降低（P〈0.05）;器官衰竭发生率较MODS组明显降低（37.5%vs85.7%,P〈0.05）;MODS组肝、肾组织IL-6mRNA表达水平显著高于正常对照组和CVVHDF组（P〈0.01）,而CVVHDF组肝、肾组织IL-10 mRNA表达水平显著高于正常对照组和MODS组（P〈0.01）。结论：连续性血液透析滤过能明显改善肾功能,CVVHDF早期应用可以降低MODS肝、肾组织IL-6/IL-10mRNA比值,有助于重建机体免疫系统内稳状态。