Citrate anticoagulation for single-needle hemodialysis: safety and efficacy

Single-needle hemodialysis can be the only option in some patients and requires full heparinization. The aim of our retrospective clinical study was to evaluate the safety and efficacy of regional citrate anticoagulation for single-needle hemodialysis. Citrate anticoagulation was performed during 41 single-needle hemodialysis procedures in 24 patients at risk of bleeding, using 4% trisodium citrate, 1 M CaCl2 and calcium-free dialysate. Safety was assessed by the percentage of procedures that were terminated prematurely or changed to another modality due to citrate-related complications and by incidence of important hypocalcemia. Efficacy was evaluated by visually assessing clot formation in the circuit. Five per cent of the procedures were terminated prematurely. Important hypocalcemia was recorded in 34% of the procedures. Anticoagulation was suboptimal in 17% of the procedures, but none of the systems clotted. The median dialyzer assessment grade was excellent. The average protocol parameters were: blood flow 244 +/- 27 mL/min, starting rate of citrate 191 +/- 19 mL/h, starting rate of calcium 6.7 +/- 1.1 mL/h. In the first hour, ionized calcium decreased in 67% of the procedures by 0.08 +/- 0.05 mmol/L. During the entire procedure, ionized calcium decreased in 80% of the cases by 0.17 +/- 0.09 mmol/L. There was a significant, but small increase in sodium (135 +/- 4 vs 137 +/- 4 mmol/L) and no increase in bicarbonate. Citrate anticoagulation during single-needle hemodialysis, according to our protocol, is safe and effective. Close monitoring of ionized calcium is mandatory. The calcium infusion rate should frequently be increased to correct hypocalcemia. The increased starting rate of calcium should be evaluated.     

枸橼酸抗凝在持续缓慢低效血液透析中的疗效和安全性

目的 观察枸橼酸抗凝应用于持续缓慢低效血液透析(SLED)的安全性及有效性.方法 前瞻性观察四川大学华西医院2011年8月至2012年9月收治的45例急性肾损伤或终末期肾病患者.所有患者血管通路均采用颈/股静脉留置双腔导管,采用费森尤斯4008sARrTplus透析机进行SLED,治疗时间为8h.4％枸橼酸钠以130 ml/h由动脉端泵入,血流量150 ml/min,无钙透析液流量200 ml/min,10％葡萄糖酸钙以40 ml/h静脉端泵入.分别在0、2、5h测定枸橼酸浓度,并观察外周血及透析器后血清游离钙水平.结果 45例患者行SLED治疗162例次,除2例次患者分别在治疗4h及6h时出现1次透析器Ⅲ°凝血需更换透析管路外,余160例次(98.8％)SLED均顺利完成.0h枸橼酸浓度为(0.14 ±0.06) mmol/L,虽然2h及5h外周血枸橼酸浓度轻度升高,但两组间差异无明显统计学意义[(1.08±0.12) mmol/L比(1.11 ±0.17) mmol/L,P＞0.05].0、2、5h的外周血游离钙水平分别为(1.04±0.13)mmol/L、(1.07±0.23) mmol/L及(1.04±0.24) mmol/L,组间差异无统计学意义(P＞0.05).2h及5h滤器后游离钙水平分别为(0.31±0.04) mmo1/L及(0.29±0.03) mmol/L.2h和5h的跨膜压分别为(104.5±17.8) mm Hg(1 mm Hg=0.133 kPa)和(109.3±20.1)mm Hg,两组间差异无统计学意义(P＞0.05).5h测定外周血凝血酶原时间及活化部分凝血活酶时间与治疗前比较差异无统计学意义(P＞0.05).在SLED治疗过程中未出现出血、血小板减少、心律失常、高钠血症、代谢性碱中毒及低血压事件.结论 枸橼酸抗凝在SLED应用中安全有效,在保证有效的局部抗凝过程下不影响体内的凝血功能,为临床医生提供了一种新型的SLED抗凝方式.     

在严重出血倾向重危患者应用枸橼酸抗凝进行连续性静脉-静脉血液滤过治疗

目的：采用枸橼酸抗凝的连续性静脉－静脉血液滤过（CVVH）治疗伴出血倾向的重危患者，观察不同临床情况下枸橼酸抗凝的疗效及安全性。方法：40例伴有出血倾向患者行CVVH治疗，采用枸橼酸抗凝。其中10例患者伴有明显肝功能损害，10例患者伴有低氧血症，其余20例患者不伴有以上两种情况。监测治疗中动脉血气，血清离子钙水平及全血活化凝血时间（WBACT）变化。结果：所有患者CVVH治疗中滤器前WBACT与治疗前相比无显著差异，而滤器后WBACT则显著延长（P＜0．05）。有肝功能损害患者治疗前存在明显代谢性酸中毒，治疗中逐步纠正；持续低氧血症患者CVVH治疗中酸中毒进行性加重；而不伴上述两种情况的患者治疗前无明显代谢性酸中毒，治疗中酸碱状况变化不明显。除伴低氧血症患者治疗中滤器前血清离子钙出现进行性下降外，其余患者治疗中部保持在正常范围。结论：存在肝功能异常患者行CVVH治疗时应用枸橼酸抗凝并无明显低钙血症或酸中毒等代谢并发症，而存在低氧血症患者应用枸橼酸抗凝则可能出现进行性加重酸中毒及低离子钙血症。     

Comparison of acetate-free citrate hemodialysis and bicarbonate hemodialysis regarding the effect of intra-dialysis hypotension and post-dialysis malaise

Compared with acetate dialysate, bicarbonate dialysate has shown beneficial effects in reducing the morbidity associated with dialysis, but a small amount of acetate in bicarbonate dialysate may evoke hypotension or malaise. Acetate‐free citrate hemodialysis (AFHD) may avoid these problems. In 44 hemodialysis patients bicarbonate hemodialysis (BHD) was conducted for three months, followed by a switch to AFHD for three months, and a further switch to bicarbonate hemodialysis (ReBHD). In BHD, AFHD and ReBHD, intra‐dialysis hypotension and post‐dialysis malaise were determined (hypotension: intra‐dialysis systolic blood pressure (SBP) was expressed as a percentage of SBP at the start of hemodialysis, malaise was assessed by a self‐reported 0 to 3 scale, 0: absence of malaise, 3: unbearable malaise). Compared with BHD, AFHD patients complained of less malaise but the intra‐dialysis blood pressure change did not differ significantly (malaise: BHD 0.73 ± 0.76 vs. AFHD 0.32 ± 0.47, P < 0.0001, end hemodialysis SBP: BHD 93.6 ± 8.9 vs. AFHD 93.8 ± 10.1, P = NS). After switching to ReBHD from AFHD, the malaise score increased (AFHD 0.32 ± 0.47 vs. ReBHD 0.77 ± 0.89, P < 0.0001) and the intra‐dialysis blood pressure dropped markedly (end hemodialysis SBP: AFHD 93.8 ± 10.1 vs. ReBHD 87.3 ± 10.5, P < 0.0001). Malaise was very severe in five patients who could not continue ReBHD. After ten days under ReBHD, ReBHD was changed to AFHD again in all patients. Although the exact mechanisms are not known, AFHD may be preferable to BHD to prevent hemodialysis‐induced hypotension and malaise.     

Forecasting correct sodium balance in hemodiafiltration procedures involving infusions.

Four patients, stable on acetate hemodialysis (AHD), were switched to acetate-free biofiltration (AFB) which differs from AHD and bicarbonate hemodialysis (BHD) in that the dialysate contains no buffer, which is given intravenously as a hypertonic (1/6 M) Na bicarbonate solution. Within the 1st month the patients developed thirst and hypertension attributed to a positive Na balance. The aim of this investigation was to check this (1) by a study based on the predictable changes induced in the body compartments of 13 patients by the infusion and ultrafiltration (UF) of a hypertonic solution and (2) by direct determination and calculation of 28 Na mass balances in BHD and AFB. The theoretical model indicated that infusion of 4.87 liters of a 166.7 mEq/l Na bicarbonate solution and UF of the same amount caused a positive balance of 233 mosm of Na. The Na mass balances showed a relationship between Na transmembrane gradient and loss or gain of Na in both methods (p less than 0.0001). The slopes of the regression lines were not significantly different but there was a highly significant difference between the y axis intercepts (p less than 0.0001), which indicates that the same Na transmembrane gradient that gives no net change of Na in BHD, induces a net gain of 240 mosm (120 mEq of Na) in AFB and that to obtain the same Na balance dialysate Na should be reduced by about 8 mEq/l in AFB. These data are the same as the theoretical forecast which could be extended to all hemodiafiltration methods in which solutions of any tonicity have to be infused, in order to correctly predict the Na balance.     

枸橼酸碳酸氢盐透析液对血液透析患者高血压的影响

目的:比较枸橼酸碳酸氢盐透析液与普通碳酸氢盐透析液治疗维持性血液透析患者透析中血压的影响。方法:20例患者随机分为两组,各10例,分别使用枸橼酸碳酸氢盐透析液和普通碳酸氢盐透析液进行透析,第一组患者使用普通碳酸氢盐透析液治疗4周后切换为枸橼酸碳酸氢盐透析液治疗4周。第二组患者直接切换为枸橼酸碳酸氢盐透析液治疗4周后再次切换成普通碳酸氢盐透析液治疗4周。记录透析前后及透析过程中的实验室数据进行统计分析。结果:(1)使用枸橼酸碳酸氢盐透析液的患者透析过程中患者的平均收缩压明显低于普通碳酸氢盐透析液透析时(P0.01),平均动脉压(MAP)较普通碳酸氢盐透析液透析时降低(P0.05);枸橼酸碳酸氢盐透析液透析时患者透析中高血压的发生率为3.3%,明显低于使用普通碳酸氢盐透析液透析时(20%,P0.01)。(2)使用不同透析液透析时患者透析前血清总钙离子与离子钙水平无统计学差异,枸橼酸碳酸氢盐透析液透析时患者透析后血清总钙离子和离子钙水平明显著低于普通碳酸氢盐透析液透析时(P0.01)。普通碳酸氢盐透析液透析时患者透后血清总钙离子及离子钙水平较透前显著升高(P0.01),使用枸橼酸碳酸氢盐透析时患者仅出现透后血清离子钙水平下降(P0.01),而透析前、后血清总钙离子水平无明显改变。(3)不同透析液透析前、后BUN均无统计学差异。虽然枸橼酸碳酸氢盐透析液透析时患者尿素清除指数(Kt/V)要略高于普通碳酸氢盐透析液透析时,但两者之间无统计学差异。两组患者均未出现严重的低血压、低钙血症及抽搐等不良反应。结论:应用枸橼酸碳酸氢盐透析液治疗的患者透析中血压的控制明显优于普通碳酸氢盐透析液。其血压控制佳、高血压发生率低,无严重低血压、抽搐以及碱中毒等不良反应。透析后离子钙浓度减低,但并未发生明显低钙血症。证实了其在临床应用的有效性和安全性。     

Citrate anticoagulation during plasma exchange in a patient with thrombotic thrombocytopenic purpura: short heparin-free hemodialysis helps to attenuate citrate load

The treatment of thrombotic thrombocytopenic purpura requires plasma exchange using fresh frozen plasma as a replacement solution once or even twice daily. If citrate anticoagulation is needed, the citrate load (both from fresh frozen plasma and citrate as an anticoagulant) can be significant, causing metabolic complications. The aim of our report is to present our experience with citrate anticoagulation in a patient with thrombotic thrombocytopenic purpura treated with daily membrane plasma exchange. Twenty-six plasma exchange procedures were performed during 20 days of treatment in a 46-year-old female. The blood flow was 98 +/- 8 mL/min; 4% trisodium citrate was infused into the arterial line (134 +/- 11 mL/h) and 1 M CaCl2 into the venous line (11.4 +/- 1.8 mL/h). Fresh frozen plasma (first 7 procedures) or cryo-poor plasma (19 procedures) were used as a replacement solution, 3176 +/- 536 mL per procedure. A total of 88,930 mL of plasma was exchanged. No serious side-effects occurred. iCa before plasma exchange was significantly higher than afterwards (1.23 +/- 0.12 vs. 1.12 +/- 0.12, P = 0.0047). Significant alkalosis occurred after three plasma exchanges (pH 7.64, bicarbonate 36.2 mmol/L), and was corrected by 3-h heparin-free hemodialysis with dialysate as follows: K 4.0 mmol/L, calcium 1.5 mmol/L, and bicarbonate set to 24 mmol/L. After dialysis, pH was 7.45 and bicarbonate 29.4 mmol/L. Another (2-h) heparin-free hemodialysis procedure was repeated after six plasma exchanges. Citrate anticoagulation can be safely performed in patients treated with plasma exchange once or twice daily. Periodically performed short heparin-free hemodialysis can correct metabolic alkalosis and attenuate the citrate load.     

Regional citrate anticoagulation in critically ill patients treated with plasma filtration and adsorption

BACKGROUND: In high-risk bleeding conditions conventional systemic anticoagulation with heparin is a contraindication to renal replacement therapy. We evaluate the feasibility and safety of regional citrate anticoagulation in high-risk bleeding conditions during coupled plasma filtration adsorption (CPFA). METHODS:Thirteen critically ill patients (9 severely burned, 4 polytraumas) with septic shock and acute renal failure treated with CPFA-CVVHD by using bicarbonate-based solutions (heparin-CPFA group, 58 sessions) or with CPFA-CVVHF using citrate (citrate-CPFA group, 36 sessions). RESULTS: Plasma flow and used cartridges showed no differences between the citrate-CPFA and heparin-CPFA groups, while lost clotted cartridges were significantly lower in the citrate-CPFA group. Blood ionized calcium (iCa2+), Ca2+ infusion, pH and bicarbonates remained constant during citrate-CPFA, with no difference between pre- and post-cartridge plasma citrate. A significant positive correlation between iCa2+ in blood and ultrafiltrate was present. CONCLUSIONS: These suits demonstrate the feasibility and safety of regional citrate anticoagulation in severely burned and polytrauma septic patients treated by CPFA.     

Does monitoring of pre-/post-dialyzer pressure difference improve efficiency in intermittent hemodialysis?

BACKGROUND: Continuous monitoring of pre-/post-dialyzer pressure difference (DeltaP) is widely used in continuous renal replacement therapies to monitor extracorporeal circuit function. The aim of this study was to verify whether DeltaP may help to identify chronic subclinical worsening of dialysis quality due to incomplete dialyzer clotting in intermittent hemodialysis. METHODS: Nine chronic hemodialysis patients were enrolled in the study and dialyzed twice (high-flux polysulfone dialyzer) with DeltaP and urea-clearance monitoring: the first session with a standard anticoagulation and the second without. To verify whether a visible clotting of the dialyzer precedes or follows a significant DeltaP increase, we checked the dialyzers for the presence of red clots after a saline flush performed when a 50% increase in DeltaP was registered. RESULTS: In the second dialysis session after a 50% increase in DeltaP (documented in 7/9 patients), all dialyzers, after saline flush, showed a visible fiber clotting but not a significant reduction (>15%) in urea clearance. In the majority of the patients (6/7), until a few minutes before complete occlusion of the extracorporeal circuit, the urea clearance did not change significantly (-8.9 +/- 12.7%). CONCLUSIONS: The usual check of the presence or absence of red clots in the dialyzer at the end of the dialysis session is enough, in the absence of red clots, to ensure that dialyzer efficiency is maintained during the whole treatment. Contrary to what is applied in CRRT, a continuous monitoring of DeltaP during intermittent hemodialysis would not significantly help to unmask unnoticed inefficient hemodialysis sessions.     

Ionic dialysance and quality control in hemodialysis

Quantification of dialysis is based on the measurement of effective urea clearance (K), dialysis dose (Kt) or normalized dialysis dose (Kt/V). During the last 20 years, Kt/V was the single parameter actually useful for quantifying dialysis efficiency, because it can be calculated from just blood or dialysate urea concentrations at the beginning and at the end of the dialysis session. However the calculation of the normalized dialysis dose (Kt/V) actually delivered to the patient cannot be performed during each dialysis session, because of the need of urea concentration measurements. Ionic dialysance is a new parameter easily measured on-line, non-invasively, automatically and without any cost during each dialysis session by a conductivity method. Because ionic dialysance has been proved equal to the effective urea clearance taking into account cardiopulmonary and access recirculation, it is becoming an actual quality-assurance parameter of the dialysis efficiency.     

Comparison of Citrate Anticoagulation During Plasma Exchange With Different Replacement Solutions

The aim of our retrospective study was to compare the application of regional citrate anticoagulation and citrate‐related side‐effects in plasma exchange (PE) with different replacement solutions. We included 35 patients treated with PE with regional citrate anticoagulation and divided them into three groups according to the replacement solution used: human albumin (HA) group (40 PE treatments), fresh frozen plasma (FFP) group (86 PE treatments), or a combination of the two (63 PE treatments). The citrate anticoagulation parameters, ionized calcium and metabolic consequences of citrate were compared. The blood flow and citrate infusion rates were similar in all groups. To maintain comparable values of ionized calcium during PE, significantly more calcium was replaced in the combination group (7.6 ± 1.3 vs. 6.2 ± 2.7 mL/h, P < 0.001) and even more in the FFP group (10.8 ± 1.7 vs. 6.2 ± 2.7 mL/h, P < 0.001) as compared to the HA group. The pH increased significantly and comparably in all groups, but the increase in bicarbonate was significantly higher in the FFP group (4.4 ± 3.0 vs. 2.6 ± 2.1 mmol/L, P = 0.01). A short, heparin‐free hemodialysis session was performed after the PE treatment, because of significant metabolic alkalosis (mainly with pH ≥ 7.5), significantly more often in the FFP group (14/86 PE, P < 0.01) as compared to the HA group (0/40), and only rarely in the combination group (2/63). To conclude, when FFP is used as a replacement solution during PE with citrate anticoagulation, significantly more calcium needs to be replaced and the increase in bicarbonate is greater during PE. The additional citrate contained in FFP, combined with frequent PE treatments, often causes significant metabolic alkalosis, which can be efficiently corrected with a short heparin‐free hemodialysis.     

A simplified protocol for individualized regional citrate anticoagulation for hemodialysis: A single-center,randomized clinical study

Introduction:The lack of individualized treatment protocols and complicated procedures are important factors limiting the use of regional citrate anticoagulation (RCA) technology in hemodialysis. This study aims to validate the safety and efficacy of a simplified individualized RCA protocol for hemodialysis.Materials and methods:From June 2019 to August 2019, 45 patients with active bleeding or bleeding tendency undergoing maintenance hemodialysis in the Nephrology Department of the First Affiliated Hospital of Nanchang University were randomly divided into a modified conventional RCA protocol group with a low-flux dialyzer, a simplified individualized RCA protocol group with a high-flux dialyzer, and a simplified individualized RCA protocol group with a low-flux dialyzer.Results:A total of 45 patients were included in this study. The mean age of the patients was 57.38 ± 19.05 years, and 78% were men. Forty-three patients completed 4 hours of hemodialysis, and the median total clotting scores in the 3 groups were 11, 12, and 12. Compared with the modified conventional RCA protocol group with a low-flux dialyzer, the 2 simplified individualized RCA protocol groups had better clotting scores for the dialyzer, arterial bubble trap, and single-pool urea clearance index (spKt/V_BUN) and lower costs. Moreover, these parameters did not differ between the 2 simplified individualized RCA protocol groups. No electrolyte or acid–base imbalances or citrate poisoning was observed in any of the 3 groups. Adverse events did not differ significantly among the 3 groups.Conclusions:The simplified individualized RCA protocol is safe, effective, and easy to implement. Therefore, this protocol can be promoted for clinical practice.Trial Registration:This study was registered in the Chinese Clinical Study Registry under registration number ChiCTR1900023801.     

27 Citrate Anticoagulation for Single‐Needle Hemodialysis: Safety and Efficacy

Background Single‐needle (SN) hemodialysis can be the only option for selected patients with difficulties with vascular access. Full heparinization is required to avoid clotting in the circuit. In patients at risk of bleeding, citrate could be the alternative anticoagulant. The aim of our retrospective clinical study was to evaluate safety and efficacy of regional citrate anticoagulation (RCA) during SN hemodialysis. Patients and methods Regional citrate anticoagulation was performed using 4% trisodium citrate, 1 m CaCl₂ and dialysate with 0 mmol/L Ca, 0.5 mmol/L Mg and 0 g/L glucose, Na was set at 138 mmol/L and HCO₃ at 28 mmol/L. Safety was assessed by percent of procedures that were terminated prematurely or changed to another modality due to RCA‐related complications and by incidence of important hypocalcemia, defined as decrease of iCa from start of dialysis > 0.2 mmol/L or decrease > 0.05 mmol/L to a value of < 0.8 mmol/L. Efficacy was evaluated by visual assessing of clot formation in arterial and venous bubble traps and dialyzer, after completing dialysis, by scoring: grade 5 (<10 fibers clotted) to 0 (>20% fibers clotted). It was considered insufficient if the grade was ≤ 3 or a significant clot in bubble traps occurred. Results In retrospective analysis of 41 protocols, important hypocalcemia was recorded in 34% of cases. 5% of procedures were terminated prematurely. Median dialyzer grade was 5 (interquartile range 4–5, N = 36). Anticoagulation was insufficient in 17% (6/36) of procedures, in these cases neither citrate infusion rate was lower nor coagulation time shorter. None of the systems clotted. Thirty protocols were filled in completely; average parameters are shown in the table below. In the first hour iCa decreased in 67% of procedures for 0.08 ± 0.05 mmol/L, those procedures had significantly lower starting calcium rate (6.4 ± 0.9 vs. 7.3 ± 1.1 mmol/L, P = 0.02) and higher starting iCa (1.02 ± 0.13 vs. 0.89 ± 0.14 mmol/L, P = 0.02). Over the entire procedure iCa decreased in 80% of cases for 0.17 ± 0.09 mmol/L, there was significant but small increase in Na (135 ± 4 vs. 137 ± 4 mmol/L, P ≤ 0.01) and no increase in HCO₃ at the end of hemodialysis ( Table A27 ).

Post‐Dilution Hemodiafiltration With a Heparin‐Grafted Polyacrylonitrile Membrane

The aim of this multicenter, prospective study was to explore the possibility of carrying out routine sessions of post‐dilution hemodiafiltration with a polyacrylonitrile membrane grafted with heparin (HeprAN) and reduced anticoagulation. Forty‐four patients from eight centers were included in the study and treated by means of post‐dilution on‐line hemodiafiltration with automatic control of TMP, according to three different modalities tested consecutively: phase 1, polyethersulfone filter primed with heparinized saline and anticoagulated with continuous infusion of unfractionated heparin 1000/h; phase 2, HeprAN membrane filter primed with saline without heparin. Anticoagulation: a 1000‐unit bolus of unfractionated heparin at the start of session followed by a second one at the end of the second dialysis hour; phase 3, same filter and priming procedure as in phase 2; anticoagulation with nadroparin calcium at the beginning of treatment. Partial or massive clotting of the dialyzer occurred in less than 1% of sessions in phase 1; 10% and 7% in phase 2; and 1% and 2% in phase 3. Clotting limited to the drip chambers was observed in 13%, 34% and 12%, respectively. The study of coagulation parameters showed a better profile when low‐molecular weight heparin (LMWH) was used in association with HeprAN membrane, while the generation of TAT complexes did not differ from that observed with the standard anticoagulation modality used in phase 1. Our results suggest that the HeprAN membrane can be used safely in routine post‐dilution hemodiafiltration with reduced doses of LMWH.     

Hemodialysis-associated induction of cytokines

The interleukin hypothesis relates chronic pathology in long-term end-stage renal disease (ESRD) patients to repeated stimulation of mononuclear cell cytokine production during hemodialysis. In vitro experiments demonstrated different possible mechanisms involved in hemodialysis-associated cytokine induction: adherence of mononuclear cells to the dialyzer membrane; complement activation, and the passage of cytokine-inducing bacterial fragments from contaminated dialysate through the dialyzer membrane into the blood. Studies investigating mononuclear cells from ESRD patients ex vivo suggest that these cells become activated during hemodialysis with complement-activating membranes and that the type of dialyzer membrane may influence mononuclear cell cytokine production in response to endotoxin. According to biological assays, plasma levels of interleukin-1 but not interleukin-6 activity seem to be elevated in ESRD patients compared to normal subjects and may increase further during treatment depending on the choice of the dialyzer membrane. However, to date, partly due to insufficient assay sensitivity and circulating inhibitors, measurements of interleukin-1, interleukin-6 and tumor necrosis factor in plasma by specific immunoassays could not finally prove elevated plasma cytokine levels in ESRD patients. Since circulating mononuclear cells are a major source of cytokines, studying the activation of these cells ex vivo seems to be the best approach to study hemodialysis-associated cytokine induction.     

When good water goes bad: how it happens, clinical consequences and possible solutions

Dialysis fluid produced by state-of-the-art water preparation and distribution is contaminated with gram-negative bacteria and cytokine-inducing substances (CIS) derived from these microorganisms. The presence of a biofilm increases the risk of continuous contamination of dialysis fluid. Depending on the type of dialyzer membrane (cellulosic vs. synthetic) and the mode of dialysis (low flux vs. high flux with backfiltration), CIS may penetrate intact dialyzer membranes, induce cytokine production in the patient's blood and contribute to chronic inflammation associated with long-term hemodialysis therapy. Measures to improve the microbiological quality of dialysis fluid are: (1) the awareness of the problem and regular testing of dialysate samples using adequate methods; (2) disinfection of the entire water preparation and distribution system on a regular basis, replacement of biofilm-containing tubings, and (3) installation of ultrafilters in the dialysate circuit in particular when high-flux hemodialysis modalities are performed.     

Control of secondary hyperparathyroidism during long-term hemodialysis

The hyperparathyroidism which occurs during long-term hemodialysis of patients with chronic renal failure has been successfully controlled without the need for subtotal parathyroidectomy. Utilizing a highly sensitive radioimmunoassay for plasma parathyroid hormone (iPTH), it was found that iPTH was correlated negatively with dialysate calcium concentration and positively with plasma phosphate concentration. Manipulation of these factors separately demonstrated that iPTH could be significantly decreased in two to three weeks by simultaneously decreasing plasma phosphate and increasing dialysate calcium. On the basis of calcium flux studies across the dialyzer, it was determined that the optimal calcium concentration in the dialysate was 8 mg/100 ml. Ten patients were treated by initially decreasing their plasma phosphate to less than 6 mg/100 ml (by giving them oral aluminum hydroxide) and using dialysis against a calcium concentration of 8 mg/100 ml. All patients have manifested a substantial and progressive decrease in plasma iPTH toward normal, with alleviation of bone pain and absence of complications, during use of this regimen.     

Expanded hemodialysis: Is anticoagulation of the dialysis circuit different from online hemodiafiltration and high-flux hemodialysis?

Expanded hemodialysis (HDx) has a high capacity for removing medium and medium-large molecules; however, there are no specific recommendations during HDx for anticoagulation of the dialysis circuit. We aimed to evaluate the differences in the efficacy of anticoagulation procedures using the venous port and 40 mg enoxaparin in HDx compared to high-flux hemodialysis (HF-HD) and postdilution online hemodiafiltration (HDF). We compared anticoagulant activity in 11 patients in HDx, HF-HD, and HDF under similar dialysis conditions. In the 33 dialysis sessions, 40 mg enoxaparin was administered through the venous port, and pre- and postdialysis antifactor Xa activity (aXa) and activated partial thromboplastin time (APTT), postdialysis clotting time of the vascular access, visual clotting score of the dialyzer, and any complications with the extracorporeal circuit or bleeding were registered. APTT postdialysis in HDx was not significantly different from that in HF-HD and HDF. Postdialysis aXa in HDx was not significantly different from that in HF-HD and HDF. We found no significant differences in visual clotting score of the dialyzer. Enoxaparin administered through the venous port was sufficient for anticoagulation within the extracorporeal circuit in HDx, HF-HD, and HDF. There were no differences in postdialysis aXa or APTT, most likely because when low molecular–weight heparin is applied through venous port, lesser enoxaparin concentration reaches the dialyzer. Thus, we conclude that the dose of enoxaparin administered through the venous port should not be adjusted according to dialysis technique.     

Measurement of backfiltration rates during hemodialysis with highly permeable membranes.

A method for determining local transmembrane fluid movement in a commercial hemodialyzer at low dialysate flow rates by measuring changes along the dialyzer length in the local concentration of a marker macromolecule added to the dialysis solution has been developed. The method was evaluated in vitro at zero net ultrafiltration using dialyzers containing polysulfone (n = 4) and cuprophane (n = 3) membranes. The local concentration of the marker macromolecule along the dialyzer length was higher than the input dialysate concentration only during experiments with dialyzers containing polysulfone membranes. These observations provide direct empirical evidence that fluid movement in the dialysate to blood direction, i.e., backfiltration, occurs during hemodialysis with this highly permeable membrane. Net rates of backfiltration for the dialyzer containing polysulfone membrane were also calculated from changes in the local concentration of the marker macromolecule and mass balance considerations. The calculated backfiltration rates increased with increasing blood flow rate and trended upward with increasing dialysate flow rate. The described methodology provides a novel approach for the further characterization of fluid and solute transport during hemodialysis with highly permeable membranes.     

Long-term citrate anticoagulation in chronic hemodialysis patients

In some cases, long-term (>3 months) citrate anticoagulation is needed in maintenance hemodialysis patients due to a persistent bleeding risk. In this retrospective observational study, we present our experience and assess its safety and effects on mineral and bone disorder parameters. Sixteen patients (mean age 67 ± 15 years) were treated with long-term citrate anticoagulation. The indications were: recurrent gastrointestinal bleeding in nine patients, heparin-induced thrombocytopenia, retroperitoneal hematoma, chronic subdural hematoma, proliferative diabetic retinopathy, vascular malformations in the brain in one patient, and others in two patients. Metabolic complications and intact parathyroid hormone (iPTH) were analyzed. Citrate anticoagulation was performed for 4 months to 6.3 years (median 12 months). Ionized calcium was stable during the procedures; hypocalcemia (<0.9 mmol/L) was rare (2.1% of procedures), and there was one case of severe symptomatic hypocalcemia. There were no clinically significant acid-base disturbances and no clotting problems. In the short term (1-3 months after starting citrate), the iPTH increased in 73% of patients (from 325 ± 310 to 591 ± 793 pg/L, P = 0.11, N = 11). In the long term (1-2 years), an increase in iPTH was observed in 3/6 patients. The time period (before/after starting citrate) was a significant predictor of iPTH using main-effects anova (P < 0.001). To conclude, long-term citrate anticoagulation in chronic hemodialysis patients is safe. Mild hypocalcemia during dialysis with citrate anticoagulation may contribute to a short- and long-term increase in iPTH in these patients. Further studies on long-term citrate anticoagulation are necessary.