Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin‐free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding. Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring. Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high‐flux dialyzer F40, Fresenius): (1) 17‐year‐old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra‐cerebral hemorrhage (2 sessions); (2) 13‐year‐old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7‐year‐old boy (hyperoxaluria, access via PermCath^® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post‐dialyzer extracorporeal serum Ca⁺⁺ (aim < 0.3 mmol/L) and pre‐dialyzer intra‐corporeal Ca⁺⁺ (aim > 0.9) were measured for every 30 min. Serum Na⁺, K⁺, base excess (BE), blood flow, blood pressure, heart rate, and blood out‐flow and in‐flow pressure were also monitored. Results: For adequate RCA (mean extracorporeal serum Ca⁺⁺ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra‐corporeal Ca⁺⁺ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra‐corporeal ACT 90 ± 12 sec. Serum Na⁺, K⁺, and BE during HD were 138 ± 2, 3.5 ± 0.3, and ?0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca⁺⁺ < 0.6 mmol/L) cured by stopping dialysis. Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.     

Modifications to bicarbonate conductivity: A way to increase phosphate removal during hemodialysis? Proof of concept

Introduction Hyperphosphatemia and cardiovascular mortality are associated particularly with end‐stage renal disease. Available therapeutic strategies (i.e., diet restriction, calcium [or not]‐based phosphate binders, calcimimetics) are associated with extrarenal blood purification. Compartmentalization of phosphate limits its depuration during hemodialysis. Several studies suggest that plasmatic pH is involved in the mobilization of phosphate from intracellular to extracellular compartments. Consequently, the efficiency of modified bicarbonate conductivity to purify blood phosphate was tested. Methods Ten hemodialysis patients with chronic hyperphosphatemia (>2.1 mmol/L) were included in the two three–sessions‐per week periods. Bicarbonate concentration was fixed at 40 mmol/L and 30 mmol/L in the first and second periods, respectively. Phosphate depuration was evaluated by phosphate mobilization clearance (K_M). Findings Although bicarbonatemia was lower during the second period (21.0 ± 2.7 vs. 24.4 ± 3.1 mmol/L, P < 0.01), no difference was observed in phosphatemia (2.4 ± 0.5 vs. 2.3 ± 0.4 mmol/L, P = NS). The in‐session variation of phosphate was lower (?1.45 ± 0.42 vs. ?1.58 ± 0.44 mmol/L, P < 0.05) and K_M was higher during the second period (82.94 ± 38.00 vs. 69.74 ± 24.48 mL/min, P < 0.05). Discussion The decrease of in‐session phosphate and the increase in K_M reflect phosphate refilling during hemodialysis. Thus, modulation of serum bicarbonate may play a role in controlling the phosphate pool. Even though correcting metabolic acidosis during hemodialysis remains important, alkaline excess can impair phosphate mobilization clearance. Clinical trials are needed to test the efficiency and relevance of a strategy where bicarbonatemia is corrected less at the beginning of sessions.     

Anticoagulation,delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD)

Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/V_urea. We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3–75.0 hours) than with heparin (5.9, IQR 8.5–27.0 hours) or no anticoagulation (17.5, IQR 9.5–32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02–3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54–1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.     

Adherence rates to ferric citrate as compared to active control in patients with end stage kidney disease on dialysis

Introduction: Oral phosphate binders are the main stay of treatment of hyperphosphatemia. Adherence rates to ferric citrate, a recently approved phosphate binder, are unknown. Methods: We conducted a post‐hoc analysis to evaluate whether adherence rates were different for ferric citrate vs. active control in 412 subjects with end stage kidney disease (ESKD) who were randomized to ferric citrate vs. active control (sevelamer carbonate and/or calcium acetate). Adherence was defined as percent of actual number of pills taken to total number of pills prescribed. Findings: There were no significant differences in baseline characteristics including gender, race/ethnicity, and age between the ferric citrate and active control groups. Baseline phosphorus, calcium, and parathyroid hormone levels were similar. Mean (SD) adherence was 81.4% (17.4) and 81.7% (15.9) in the ferric citrate and active control groups, respectively (P = 0.88). Adherence remained similar between both groups after adjusting for gender, race/ethnicity, age, cardiovascular disease (CVD), and diabetic nephropathy (mean [95% CI]: 81.4% [78.2, 84.6] and 81.5% [77.7, 85.2] for ferric citrate and active control, respectively). Gender, race/ethnicity, age, and diagnosis of diabetic nephropathy did not influence adherence to the prescribed phosphate binder. Subjects with CVD had lower adherence rates to phosphate binder; this was significant only in the active control group. Discussion: Adherence rates to the phosphate binder, ferric citrate, were similar to adherence rates to active control. Similar adherence rates to ferric citrate are notable since tolerance to active control was an entry criteria and the study was open label. Gender, race/ethnicity, nor age influenced adherence.     

Antibiotic lock: In vitro stability of gentamicin and sodium citrate stored in dialysis catheters at 37 °C

Catheter‐related bacteremia (CRB) is a major cause of morbidity and mortality especially among patients receiving hemodialysis. Antibiotic lock therapy represents a promising technique in the treatment of CRB. Several studies have evaluated antibiotics in combination with heparin as an interdialytic locking solution for prophylaxis of CRB. The objective of this study was to evaluate the stability of gentamicin and sodium citrate in hemodialysis catheters as an interdialytic lock. Solutions containing gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) were prepared individually and in combination. The solutions were instilled into dialysis catheters and stored at 37 °C for 96 h. Samples were withdrawn randomly from catheter lumens at 24‐hour intervals for 4 days and stored at ?20 °C until analysis. The samples were analyzed with validated, stability‐indicating HPLC assays. The luminal concentration of gentamicin 2.5 mg/mL, sodium citrate 40 mg/mL (4%), and the combination was determined on study days 0, 1, 2, 3, and 4. When gentamicin was combined with sodium citrate and stored at 37 °C in dialysis catheters, the solution showed no decrease in either the gentamicin or the sodium citrate concentrations over the 96‐hour study period. The percent of the original concentration at 96 h was 102.4±1.03 for gentamicin and 102.9±1.25 for citrate (P=0.5556). The combination of gentamicin 2.5 mg/mL and sodium citrate 40 mg/mL (4%) can be retained in hemodialysis catheters for at least 96 h at 37 °C with no evidence of degradation.     

High sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation in patients with acute liver failure and cerebral edema

Introduction: Acute liver failure is associated with a high mortality rate. Induction of plasma hypertonicity with mannitol or hypertonic saline remains the cornerstone in the management of resultant cerebral edema. Significant disadvantages of this approach include poor or unpredictable control of serum sodium concentration and volume expansion, among others. Methods: We used high sodium continuous veno‐venous hemodialysis with regional citrate anticoagulation and online dialysate generation to accurately control the serum sodium in eleven patients with acute liver failure, renal failure, and cerebral edema. We used a Fresenius 2008 K/K2 machine in hemodialysis mode to deliver a blood flow of 60 ml/minute and dialysate flow of 400 ml/minute. Our previously published protocol results in complete removal of infused citrate by the dialyzer. On‐line clearance calculations were used to model the time required to reach the target serum sodium. Findings: All patients achieved serum sodium within 2 mEq/L of target without fluctuations or rebound. Nine patients survived without requiring liver transplantation and two died despite reaching the prescribed serum sodium target. We did not encounter any citrate toxicity. Discussion: We describe a novel approach for delivering continuous osmotherapy to patients with acute liver failure, renal failure, and cerebral edema. In comparison to standard therapy, the described modality enables precise titration of serum sodium without undesirable fluctuations in extracellular fluid volume. A particular advantage is zero delivery of citrate to this vulnerable group of patients with acute liver failure.     

Dialysate bicarbonate variation in maintenance hemodiafiltration patients: Impact on serum bicarbonate,intradialytic hypotension and interdialytic weight gain

Introduction: The dialysate bicarbonate (DB) influences the acid‐base balance in dialysis patients. Very low and high serum bicarbonate (SB) have been related with a higher mortality. Acid‐base balance also has been associated with hemodynamic effects in these patients. The trial aim was to compare the effect of DB concentration variation on SB levels in maintenance hemodiafiltration (HDF) patients and the effect on intradialytic hypotension and interdialytic weight gain. Methods: A prospective study, with 9 months of follow‐up, involving 93 patients, divided in two groups: group 1 and group 2 with a DB of 34 mmol/L and 30 mmol/L, respectively, with monitoring of pre and post HDF SB, intradialytic hypotension, and interdialytic weight gain. Findings: Pre dialysis SB was higher in group 1: median concentration of 22.7 mmol/L vs. 21.1 mmol/L (P < 0.001). Post dialysis SB levels were higher in group 1: median concentration of 28.0 mmol/L vs. 25.3 mmol/L (P < 0.001). Post dialysis SB in alkalotic range was only detected in group 1 (51.2% of the patients). No significant differences were detected in intradialytic hypotension rate [28.0 vs. 27.4 episodes per 1000 sessions in group 1 and 2, respectively, (P = 0.906)] or in average interdialytic weight gain [2.9% vs. 3.0% in group 1 and 2, respectively, (P = 0.710)]. Discussion: DB of 30 mmol/L appears to be associated with SB levels closer to physiological levels than 34 mmol/L. The bicarbonate dialysate, in the tested concentrations, did not appear to have a significant impact on intradialytic hypotension and interdialytic weight gain in maintenance HDF patients.     

Reduced protein bound uraemic toxins in vegetarian kidney failure patients treated by haemodiafiltration

Introduction Indoxyl sulfate (IS) and p cresyl sulfate (PCS) are protein bound toxins which accumulate with chronic kidney disease. Haemodiafiltration (HDF) increases middle molecule clearances and has been suggested to increase IS and PCS clearance. We therefore wished to establish whether higher convective clearances with HDF would reduce IS and PCS concentrations. Methods We measured total plasma IS and PCS in a cohort of 138 CKD5d patients treated by On‐line HDF (Ol‐HDF), by high pressure liquid chromatography. Findings Mean patient age was 64.6 ± 16.5 years, 60.1% male, 57.3% diabetic, median dialysis vintage 25.9 months (12.4–62.0). The mean ICS concentration was 79.8 ± 56.4 umol/L and PCS 140.3 ± 101.8 umol/L. On multivariate analysis, IS was associated with serum albumin (β 4.31,P < 0.001), and negatively with residual renal function (β‐4.1,P = 0.02) and vegetarian diet(β‐28.3, P = 0.048) and PCS negatively with log C reactive protein (β‐75.8, P < 0.001) and vegetarian diet (β‐109, P = 0.001). Vegetarian patients had lower IS and PCS levels (median 41.5 (24.2–71.9) vs. 78.1 (49.5–107.5) and PCS (41.6 (14.2–178.3) vs. 127.3 (77.4–205.6) µmol/L, respectively, P < 0.05. Vegetarian patients had lower preOl‐HDF serum urea, and phosphate (13.8 ±3.8 vs. 18.4 ± 5.2 mmol/L, and 1.33 ± 0.21 vs. 1.58 ± 0.45 mmol/L), and estimated urea nitrogen intake (1.25 ± 0.28 vs. 1.62 ± 0.5 g/kg/day), respectively, all P < 0.05. Discussion Plasma IS and PCS concentrations were not lower with Ol‐HDF compared to previous studies in haemodialysis patients. However those eating a vegetarian diet had reduced IS and PCS concentrations. Although this could be due to differences in dietary protein intake, a vegetarian diet may also potentially reduce IS and PCS production by the intestinal microbiome.     

Effects of citrate‐enriched bicarbonate based dialysate on anticoagulation and dialyzer reuse in maintenance hemodialysis patients

Systemic anticoagulation with unfractionated heparin is commonly used in maintenance hemodialysis (HD), but it increases the risk of bleeding complications. We investigated whether the use of citrate‐enriched bicarbonate based dialysate (CD) would reduce systemic anticoagulation without compromising the efficacy of reprocessed dialyzers. This is a crossover study in which half of a total of 30 patients initially underwent HD with acetate‐enriched bicarbonate based dialysate and a standard heparin dose of ～100 IU/kg (Treatment A), whereas the remaining patients were treated with CD and a 30% reduced heparin dose (Treatment B). After 12 consecutive HD sessions in each treatment, the dialysate and heparin doses were reversed, then followed for another period of 12 HD sessions. The two treatment phases were split by a washout period of six HD sessions using acetate‐enriched bicarbonate based dialysate and standard heparin dose. Systemic anticoagulation was higher in Treatment A. The activated partial thromboplastin time at the end of HD session was 68 ± 36 seconds in Treatment A and 47 ± 16 seconds in Treatment B (P = 0.005). Sixty‐eight percent of the dialyzers remained adequate until the 12th use in Treatment A and 61% did so in Treatment B (P = 0.63). Patients had three and 24 cramps episodes during Treatment A and B, respectively (P < 0.001). Nine and 26 symptomatic intradialytic hypotension episodes were seen in Treatment A and B, respectively, (P = 0.003). In conclusion, the use of CD had a favorable effect on anticoagulation in the extracorporeal circuit in patients on maintenance HD, but it was also associated with more hypotension and cramps.     

Outcomes of Severe Methanol Intoxication Treated with Hemodialysis: Report of Seven Cases and Review of Literature

To identify factors associated with the outcome of severe methanol intoxication treated with hemodialysis, we analyzed the clinical course of 7 patients admitted with serum methanol level higher than 50 mg/dL, and therefore requiring hemodialysis. Four patients (group A) had adverse outcomes (1 death, 3 severe neurological deficits and/or blindness) and 3 patients (group B) had no adverse outcomes. Compared to group B, group A appeared to have a longer delay between ingestion of methanol and arrival at the emergency department (ED), a longer wait in the ED until ethanol infusion was started (3.6 ± 2.7 vs 1.3 ± 0.9 hr, p < 0.05), and, on admission, higher serum methanol (504 ± 219 vs 321 ± 228 mg/dL, p < 0.05), higher serum osmolality (460.5 ± 98.2 vs 397.6 ± 52.3 mOsm/kg, p < 0.05), higher serum osmolal gap (162.6 ± 76.7 vs 105.6 ± 52.9 mOsm/kg, p < 0.05), lower arterial pH (6.86 ± 0.08 vs 7.38 ± 0.16, p < 0.01), lower serum bicarbonate (4.6 ± 1.6 vs 19.9 ± 5.7 mmol/L, p < 0.01), and higher serum anion gap (36.5 ± 1.3 vs 14.3 ± 6.7 mEq/L, p < 0.01). Delay in the ED until hemodialysis was started did not differ (group A 6.4 ± 2.6 hr, group B 5.3 ± 3.5 hr), while duration of hemodialysis until serum methanol levels became permanently undetectable was longer in group A (15.0 ± 0.5 vs 8.4 ± 4.4 hr, p < 0.01). The ingested dose of methanol and the delay between ingestion and initiation of therapy to block methanol metabolism (ethanol infusion) and remove methanol from the body (hemodialysis) appear to be the critical factors influencing the outcome of methanol intoxication. Early diagnosis and initiation of treatment before substantial parts of the ingested methanol have been metabolized are of paramount importance in ensuring a favorable outcome.     

Increased dialyzer reuse with citrate dialysate

Dialyzer reuse is limited by the clotting of blood, which blocks the fibers and reduces the membrane surface area. Clotting during treatment may also reduce dialysis efficiency and potentially decrease delivered dose, Kt/V(urea). A new dialysate containing citric acid, instead of the standard acetic acid, as the acidifying agent has become available and is associated with reduced clotting during acute dialysis treatments. The effect of citric acid dialysate on dialyzer reuse was evaluated in this prospective, controlled, multicenter study involving maintenance hemodialysis patients. A total of 105 patients from five dialysis units were switched to the new dialysate and new dialyzers. Reuse outcome on the new dialysate was compared with the reuse on the regular acetic acid containing bicarbonate dialysate (controls). The overall reuse with citrate dialysate increased significantly from 15.1 +/- 9.4 to 18 +/- 10.0 (mean +/- SD) on regular and citrate dialysate, respectively (p = 0.0003). The most significant increase was seen in those patients who had limited reuse before the switch to citrate dialysate; 51, 59, and 134% increases occurred in those with 10 to 15, 5 to 10, and < 5 reuses at controls, respectively. Interestingly, the 10 patients with 10 or fewer reuses had significantly lower Kt/V(urea) at baseline (before the switch to citric acid dialysate) than those with > 10 reuses (1.23 +/- 0.23 vs. 1.47 +/- 0.23, respectively, p = 0.009). The Kt/V(urea) increased to 1.41 +/- 0.31 after the switch in the low-reuse group but the increase did not reach statistical significance (p = 0.07). The results from this study show that citric acid-containing dialysate is associated with increase in dialyzer reuse and appears to be related to reduced clotting.     

Extracellular Volume Changes and Blood Pressure Levels in Hemodialysis Patients

Background: Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post‐HD body weight (BW) over a period of 3 to 4 months. Methods: During a period of 3–4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143–141 mmol/L to 139–138 mmol/L. Extracellular volume (ECV) was measured with a multiple‐frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical. Results: Group 1 showed a significant reduction during the entire 48‐hour period in systolic (156 ± 16 mmHg vs. 140 ± 14 mmHg, P = 0.030) and diastolic BP (97 ± 12 mmHg vs. 87 ± 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 ± 13 vs. 105 ± 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 ± 15 mmHg vs. 138 ± 14 mmHg, P = 0.007; diastolic BP 97 ± 12 mmHg vs. 85 ± 9 mmHg, P = 0.009) than during the day (157 ± 18 mmHg vs. 142 ± 15 mmHg, P = 0.067; diastolic BP 97 ± 13 mmHg vs. 90 ± 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48‐hour period (76 ± 24% vs. 46 ± 28%, P = 0.043) as well as in night systolic load (75 ± 21% vs. 41 ± 30%, P = 0.015) and night diastolic load (67 ± 32% vs. 39 ± 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2. Conclusions: The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.     

Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis—sevelamer hydrochloride,calcium carbonate,and bixalomer

The serum bicarbonate (HCO₃^–) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end‐stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO₃^– levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO₃^– level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO₃^– levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P < 0.05). Metabolic acidosis was not observed in four patients (serum HCO₃^– level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer.     

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: a technical study

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4‐fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet^® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca‐phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet^® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet^® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet^® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.     

Utility of citrate dialysate in management of acute kidney injury in children

Dialysis concentrate acidified with citrate as opposed to acetate has been reported to prevent clotting in hemodialysis circuits, and improve dialysis efficiency in adults. There is no information on its use in children. The purpose of the study was to evaluate the utility of citrate dialysate for renal replacement therapy in a pediatric population with acute kidney injury. We performed a retrospective review of our experience using Citrasate^® concentrate from December 2007 to August 2009. All treatments were provided using the Fresenius 2008 dialysis machine. Citrasate^® was utilized in 7 children aged 60.3±51.0 months (mean±SD), range 13 months to 12 years. The number of treatments varied from 4 to 31 (mean 12±8 treatments) for a total of 89 treatments. Rare sporadic mild hypocalcemia was noted but could not be definitively linked with the use of Citrasate^®. Four children also required low‐dose heparin (3.6–15 U/kg/h) due to clotting. Activated clotting times (when checked) were not affected by this low‐dose heparin therapy. Some degree of clotting occurred in 21 of 89 (23.5%) treatments. Early termination of treatment due to thrombosis was required in 7 of 89 (7.8%) treatments. In summary, use of Citrasate^® dialysis concentrate was well tolerated in critically ill children with acute kidney injury. Citrasate^® reduced but did not completely eliminate the need for heparin in our population. Further study in a more diverse population would be helpful.     

Synergistic effect of citrate dispersant and capping polymers on controlling size growth of ultrafine copper nanoparticles

In this paper, we studied the synergistic effect of sodium citrate dispersant and polyvinylpyrrolidone or polyvinylalcol capping polymer on controlling the size of copper nanoparticles (CuNPs) that were prepared by the chemical reduction method. The CuNPs were characterised by using ultraviolet–visible (UV–Vis) spectroscopy, transmission electron microscopy, and X-ray diffraction techniques. The size of the nanoparticles could be predicted via their UV–Vis absorbance. In the presence of capping polymers, the size of CuNPs was significantly changed, ranging from 2 ± 1 to 20 ± 7 nm with and without sodium citrate dispersant, respectively. Moreover, surface plasmon resonance of ultrafine CuNPs (2 nm in diameter) could be observed in the short wavelength region by using UV–Vis spectra. Our finding, could offer a new synthetic approach to the production of highly stable, small-sized CuNPs.     

Experimental study on a new type citrate anticoagulant hemodialysate in dogs

Objective:  In this study, we initiated a new hemodialysate with citrate buffer, observed the factors that influence the citrate concentration of solution in hollow fibers when using citrate hemodialysate, and observed the anticoagulant effect and safety of the citrate hemodialysate in the experiment in dogs. Methods:  Ten dogs were given intermittent hemodialysis and were divided into 3 groups according to hemodialysis procedures. Group 1 was saline‐flush hemodialysed with bicarbonate hemodialysate; Group 2 was hemodialysed with citrate hemodialysis without any anticoagulant; Group 3 was hemodialysed with bicarbonate hemodialysate and heparin. ACT, Ca⁺⁺, BUN, Cr, ALT, AST, TBIL, DBIL, Na⁺, Cl⁻,     , and venous pressure were monitored in the animals of each group during hemodialysis. Results:  During the hemodialysis in Group 1, venous pressure increased lastingly, resulting in the failure of hemodialysis for 2 hours. Hemodialysis for 2 hours in Group 2 were all finished successfully. ACT was extended and Ca⁺⁺ decreased obviously in the venous end during hemodialysis. And ALT, AST, Ca⁺⁺, K⁺, Na⁺, Cl⁻,     after the hemodialysis in Group 2 were not changed (P > 0.05). Moreover, the clearance rate of the dialyzers with citrate dialysate increased significantly compared with those of saline‐flush and heparin anticoagulation. Conclusions:  The anticoagulant and dialytic effects of the new type citrate hemodialysis are satisfactory and better than that of saline‐flush.     

Hemodialysis‐induced regional left ventricular systolic dysfunction

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4‐hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD‐induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD‐induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Higher cTnT (0.060 ± 0.030 vs. 0.048 ± 0.015 ng/mL, P = 0.023), phosphate (2.07 ± 0.50 vs. 1.49 ± 0.96 mmol/L, P = 0.001), UFR (11.00 ± 3.89 vs. 8.30 ± 2.66 mL/Kg/h, P = 0.039) and lower albumin (37.83 ± 4.48 vs. 38.38 ± 2.53 g/L, P = 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR = 1.047, 95%CI 1.155–4.732, P = 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate.     

Stimulated sweating as a therapy to reduce interdialytic weight gain and improve potassium balance in chronic hemodialysis patients: A pilot study

Controlling the extracellular volume in hemodialysis patients is a difficult task. The aim of this study was to evaluate the capacity of different methods of stimulated sweating to reduce mean interdialytic weight gain (IWG), to improve blood pressure regulation, and potassium/urea balance. Two center, crossover pilot study. In Lausanne, hemodialysis patients took four hot‐water baths a week, 30 minutes each, on nondialysis days during 1 month. In Sfax, patients visited the local Hammam Center four times a week. Hemodynamic parameters were recorded, and weekly laboratory analysis was performed. Results were compared with a preceding 1‐month control period. In Lausanne, five patients (all men, median age 55 years) participated. Bathing temperature was (mean ± standard deviation) 41.2 ± 3°C and sweating‐induced weight loss 600 ± 500 g. Mean IWG (control vs. intervention period) decreased from 2.3 ± 0.9 to 1.8 ± 1 kg (P = 0.004), Systolic blood pressure from 139 ± 21 to 136 ± 22 mmHg (P = 0.4), and diastolic blood pressure form 79 ± 12 to 75 ± 13 mmHg (P = 0.08); antihypertensive therapy could be reduced from 2.8 ± 0.4 to 1.9 ± 0.5 antihypertensive drugs per patient (P = 0.01). In Sfax (n = 9, median age 46 years), weight loss per Hammam session was 420 ± 100 g. No differences were found in IWG or BP, but predialysis serum potassium level decreased from 5.9 ± 0.8 to 5.5 ± 0.9 mmol/L (P = 0.04) and urea from 26.9 ± 6 to 23.1 ± 6 mmol/L (P = 0.02). Hot‐water baths appear to be a safe way to reduce IWG in selected hemodialysis patients. Hammam visits reduce serum potassium and urea levels, but not IWG. More data in larger patient groups are necessary before definite conclusion can be drawn.     

Rationale and study design of a three‐period, 58‐week trial of ferric citrate as a phosphate binder in patients with ESRD on dialysis

Chronic kidney disease associated mineral and bone disorders arise as a result of aberrant bone mineral metabolism in patients with advancing levels of renal dysfunction and end‐stage renal disease. One of the cornerstones of treatment is the use of phosphate‐binding agents. We describe the rationale and study design for a clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder. This trial is a three‐period, international, multicenter, randomized, controlled clinical trial to assess the safety and efficacy of ferric citrate as a phosphate binder, consisting of a 2‐week washout period, a 52‐week safety assessment period in which subjects are randomized to ferric citrate or active control, and a 4‐week efficacy assessment period in which subjects randomized to ferric citrate in the safety assessment period are randomized to ferric citrate or placebo. Eligible subjects include end‐stage renal disease patients who have been treated with thrice‐weekly hemodialysis or peritoneal dialysis for at least 3 months in dialysis clinics in the United States and Israel. Primary outcome measure will be the effect of ferric citrate vs. placebo on the change in serum phosphorus. Safety assessments will be performed by monitoring adverse events, concomitant medication use, and sequential blood chemistries (including iron parameters, phosphorus, and calcium). This three‐period trial will assess the efficacy of ferric citrate as a phosphate binder. If proven safe and efficacious, ferric citrate will likely provide an additional phosphate binder to treat chronic kidney disease associated mineral and bone disorders.