Bicarbonate Dialysis Research Articles

Bicarbonate dialysis compared to hemodiafiltration on glycemic excursions in patients with end-stage renal disease with and without type 2 diabetes mellitus

AimTo evaluate the effects on glycemic excursions during bicarbonate dialysis (BHD) compared to hemodiafiltration (HDF) in type 2 diabetic or not diabetic patients affected by end-stage renal disease (ESRD). Material and MethodsThirty-six patients (20 affected by type 2 diabetes mellitus, and 16 not diabetic patients) were evaluated and underwent BHD dialysis, followed by HDF dialysis two days later. All patients underwent also glucose continuous monitoring system, using iPro Continuous Glucose Monitor System (Medtronic MiniMed) starting just before the BHD, and ending five days later, two days after the HDF dialysis. Glycemic control was estimated as the mean blood glucose (MBG), the area under the glucose curve above 70mg/dl (AUC>70) or 180mg/dl (AUC>180), and the percentage of time above 70mg/dl (t>70) or 180mg/dl (t>180). Intraday glycemic variability was assessed as the standard deviation (SD), M value, and the mean amplitude of glycemic excursions (MAGE). Day-to-day glycemic variability was assessed as the mean of daily difference (MODD), that is the mean of the absolute difference among glucose values taken on 2 consecutive days at the same time. Resultsglycemic control was better with HDF: MBG, and AUC>180 were lower during HDF compared do BHD. We also observed a significant decrease of glycemic excursions during HDF dialysis: SD, M value, and the MAGE value were lower with HDF. The MODD value was significantly changed in BHD group, while no differences were recorded during HDF. ConclusionHDF seems to greater reduce glycemic excursions during the treatment compared to BHD.

Calcium balance in pediatric online hemodiafiltration: Beware of sodium and bicarbonate in the dialysate

BackgroundOnline hemodiafiltration (oHDF) is increasingly used in children; we treated 28 children since 2009, adapting this technique to pediatric patients. MethodsIn this service evaluation audit, we assessed plasma electrolytes to evaluate the evolution of total (tCa) and ionized (iCa) during a session, as well as dialysate calcium (dCa) concentrations. ResultsUsing a 1.25 mmol Ca/L-dialysate, both tCa and iCa decreased during the session, with iCa falling below 1.1 mmol/L in 4/5 patients. In contrast, using a 1.5 mmol Ca/L-dialysate, iCa remained normal in all patients. Major discrepancies were observed between the expected and the measured dCa: 1.25 vs. 1.01 (0.83–1.04), and 1.5 vs. 1.47 (0.85–1.75) mmol/L, respectively (results presented as median [range]). These differences were explained by the modality of reconstituting dialysate: increasing bicarbonates and/or decreasing sodium requested in the dialysate decreases calcium extraction from the acid preparation. Proof of concept was given when requesting in an “ex-vivo” setting modifications in the requested sodium and bicarbonate in dialysate directly on the Fresenius machine. ConclusionNephrologists should be aware that “high bicarbonate and/or low sodium” requirements in oHDF decrease calcium in the dialysate.

Carbon Dioxide and Acetate-Free Biofiltration: A Relationship to be Investigated.

As the name reveals, acetate-free biofiltration (AFB) is featured by lack of acetate and this would seem to allow better hemodynamic stability. However, AFB also has a unique characteristic of carbon dioxide (CO2 )-free dialysate, whereas all other modern dialysis techniques imply an overload of CO2 from dialysate to the patient. This notwithstanding the role of CO2 in tolerance to dialysis treatment, both AFB and all other dialysis techniques seem not investigated in due depth. Specifically, the amount of CO2 coming back to the patient's bloodstream during AFB and bicarbonate dialysis (BD) is unknown. We measured partial pressure of CO2 (pCO2 ) in blood samples withdrawn from the venous line of the extracorporeal circuit during BD and subsequently during AFB in 22 stable chronic hemodialysis outpatients. The amount of CO2 coming back to the patient's bloodstream is higher in BD (59.1 ± 4.0 mmol/L) than in AFB (42.8 ± 4.5 mmol/L, P < 0.0001). Such difference exceeds 30%. Moreover, shifting from BD to AFB shows, notably for each patient, the reduction of pCO2 toward physiological values. BD implies CO2 overload from dialysate, whereas AFB does not. Further studies are required to evaluate if AFB would be the most appropriate dialysis technique in patients affected by chronic, but especially acute, lung diseases.

Hypersensitivity reactions to acetate in the bicarbonate dialysate in a patient undergoing pre-dilution online hemodiafiltration.

A 63-year-old male patient first experienced recurrent hypotensive episode during the dialysis session just after switching the mode from hemodialysis to online hemodiafiltration (OL-HDF) with infusion in pre-dilution of the bicarbonate dialysate containing 9.2mEq/L of acetate. Peripheral eosinophil count and serum IgE were both elevated to 16,440/μL and 2000IU/L. The reactions promptly dissolved with substitution of acetate-free solution. This case illustrated that pre-dilution OL-HDF can induce an occult hypersensitivity to acetate in the standard bicarbonate dialysate.

Eco-dialysis: the financial and ecological costs of dialysis waste products: is a 'cradle-to-cradle' model feasible for planet-friendly haemodialysis waste management?

Approximately 2 million chronic haemodialysis patients produce over 2,000,000 tons of waste per year that includes about 600,000 tons of potentially hazardous waste. The aim of the present study was to analyse the characteristics of the waste that is produced through chronic haemodialysis in an effort to identify strategies to reduce its environmental and financial impact. The study included three dialysis machines and disposables for bicarbonate dialysis, haemodiafiltration (HFR) and lactate dialysis. Hazardous waste is defined as waste that comes into contact with bodily fluids. The weight and cost of waste management was evaluated by various policies of differentiation, ranging from a careful-optimal differentiation to a careless one. The amount of time needed for optimal management was recorded in 30 dialysis sessions. Non-hazardous materials were assessed for potential recycling. The amount of plastic waste that is produced per dialysis session ranges from 1.5 to 8 kg (from 1.1 to 8 kg of potentially hazardous waste), depending upon the type of dialysis machine and supplies, differentiation and emptying policies. The financial cost of waste disposal is high, and is mainly related to hazardous waste disposal, with costs ranging from 2.2 to 16 Euro per session (2.7-21 USD) depending on the waste management policy. The average amount of time needed for careful, optimal differentiation disposal is approximately 1 minute for a haemodialysis session and 2 minutes for HFR. The ecological cost is likewise high: less than one-third of non-hazardous waste (23-28%) is potentially recyclable, while the use of different types of plastic, glues, inks and labels prevents the remaining materials from being recycled. Acknowledging the problem of waste management in dialysis could lead to savings of hundreds of millions of Dollars and to the reuse and recycling of hundreds of tons of plastic waste per year on a world-wide scale with considerable financial and ecological savings.

Citrate versus Acetate-Based Dialysate in On-Line Haemodiafiltration. A Prospective Cross-Over Study

Background and Aims: A bicarbonate dialysate acidified with citrate (CD) has been reported to have local anticoagulant effect and improves biocompatibility. This study examines the effect of CD on dialysis efficiency, coagulation, acid-base status, electrolytes, and inflammation in patients in on-line hemodiafiltration (OL-HDF). Methods: 35 patients in OL-HDF were enrolled in a prospective, cross-over study for a 24-week period and two phases alternating CD and acetate dialysate fluid (AD). Parameters on study were predialysis levels of bicarbonate and ionic calcium, reactive C Protein (CRP), and beta-2 microglobulin (B2MG) and postdialysis levels of activated tromboplastine time, bicarbonate, and ionized calcium. Results: No significant differences in coagulation parameters, pH, and predialysis bicarbonate were found. The postdialysis bicarbonate and postdialysis calcium were lower with CD. Dialysis efficiency was greater with CD. Regarding inflammatory parameters, both CRP and B2MG were lower using CD. Conclusion: The use of CD is safe and effective in OL-HDF, and it improves dialysis efficacy, postdialysis alkalosis, and inflammation.

Changes of Serum Calcium, Magnesium and Parathyroid Hormone Induced by Hemodialysis with Citrate-Enriched Dialysis Solution

Background/Aims: In recent years, one of technical attempts to improve biocompatibility and tolerability of the hemodialysis procedure is the substitution of acetate in dialysis solution with citrate. The aim of our study was to compare two dialysis solutions: traditional bicarbonate dialysis solution containing acetate (3 mmol/L) (solution A); and (solution C) commercially produced citrate-enriched bicarbonate dialysis solution (0.8 mmol/L citrate). Methods: Patients from a single hemodialysis center (N=126) were included in the study. Both conventional low-flux hemodialysis and on-line hemodiafiltration procedures were studied. Both dialysis solutions contained identical calcium (1.5 mmol/L) and magnesium (0.5 mmol/L) concentrations. Results: Parathyroid hormone (iPTH) concentration decreased during procedures with solution A by 64%. On the contrary, when solution C was used, iPTH concentration increased insignificantly by 4%. For solution A, serum calcium and magnesium increased during procedures in patients with predialysis concentrations lower than 2.33 and 0.76 mmol/L, respectively. In procedures with dialysis solution C these concentrations were significantly lower: 2.19 mmol/L for Ca and 0.68 mmol/L for Mg. Conclusion: Our study clearly shows that the substitution of part of acetate with citrate in dialysis solution significantly influences changes of serum calcium, magnesium and parathyroid hormone concentrations during hemodialysis and hemodiafiltration procedures.

A Randomized Controlled Study on the Effects of Acetate‐Free Biofiltration on Organic Anions and Acid‐Base Balance in Hemodialysis Patients

Metabolic acidosis correction is achieved by the transfer of bicarbonate and other buffer anions in dialysis. The aim of this study was to evaluate changes in the main anions of intermediary metabolism on standard hemodiafiltration (HDF) and on acetate-free biofiltration (AFB). A prospective, in-center, crossover study was carried out with 22 patients on maintenance dialysis. Patients were randomly assigned to start with 12 successive sessions of standard HDF with bicarbonate (34 mmol/L) and acetate dialysate (3 mmol/L) or 12 successive sessions of AFB without base in the dialysate. Acetate increased significantly during the standard HDF session from 0.078 ± 0.062 mmol/L to 0.156 ± 0.128 mmol/L (P < 0.05) and remained unchanged at 0.044 ± 0.034 mmol and 0.055 ± 0.028 mmol/L in AFB modality. Differences in the acetate levels were observed at two hours (P < 0.005), at the end (P < 0.005) and thirty minutes after the session between HDF and AFB (P < 0.05). There were significantly more patients above the normal range in HDF group than AFB group (68.1% vs 4.5% P < 0.005) postdialysis and 30 minutes later. Serum lactate and pyruvate concentrations decreased during the sessions without differences between modalities. Citrate decreased only in the AFB group (P < 0.05). Acetoacetate and betahydroxybutyrate increased in both modalities, but the highest betahydroxybutyrate values were detected in HDF (P < 0.05). The sum of postdialysis unusual measured organic anions (OA) were higher in HDF compared to AFB (P < 0.05). AFB achieves an optimal control of acid-base equilibrium through a bicarbonate substitution fluid. It also prevents hyperacetatemia and restores internal homeostasis with less production of intermediary metabolites.

Correction of metabolic acidosis in hemodialysis: consequences on serum leptin and mineral metabolism.

Hyperleptinemia and metabolic acidosis (MA) are frequently observed in patients on hemodialysis (HD). While the role of leptin in patients on HD is not completely understood, HD only partially corrects MA. Both leptin and acidosis have effect on bone disease. The goal of the present study was to evaluate the effects of MA correction on chronic kidney disease-mineral and bone disorder laboratory parameters and leptin levels. Forty-eight patients on HD, aged 43±19 years, were prospectively studied. Individual adjustments in the bicarbonate dialysate concentration were made to maintain pre-dialysis concentration≥22 mEq/l. Blood gas analysis was done monthly for 4 months (M1-M4). From M0 to M4, serum albumin increased (from 3.5 ±0.3 to 4.0±0.3 g/l, p<0.0001) while β2 microglobulin decreased (from 27.6±8.3 to 25.8±6.8 µg/ml, p=0.025). Serum leptin decreased in all but three patients, as well as leptin/adiponectin ratio (p<0.0001). There was a decrease in ionized serum calcium (from 5.0±0.5 to 4.7±0.5 mg/dl, p =0.002) and an increase in parathyroid hormone (PTH) [from 191 (85, 459) to 446 pg/ml (212, 983), p<0.0001] and in serum phosphate (from 5.4±1.4 to 5.8±1.1 mg/dl, p=0.048). MA correction in HD patients can decrease leptin, an atherogenic marker. The impact of such treatment extends to uremic bone disease, as decrease in serum calcium and increase in PTH. However, this could be an undesirable effect because it may aggravate a secondary hyperparathyroidism. Whether the reduction in leptin levels has impact on outcomes in patients on hemodialysis deserves further investigation.

A case of anaphylactoid reaction to acetate in acetate-containing bicarbonate dialysate.

A 35-year-old man with end-stage kidney disease due to chronic glomerulonephritis was admitted to our hospital to start maintenance hemodialysis (HD). One hour after starting the first session of HD, he experienced general pruritus, urticaria, and dyspnea. Signs and symptoms were resolved by discontinuing HD and administrating an antihistamine drug; HD-associated anaphylactoid reactions were therefore suspected. Over the next few HD sessions, we changed the dialysis membrane, anticoagulant, HD circuit and needle, in that order, but general pruritus and urticaria again appeared within 3h after starting each session of HD. Finally, when we changed the dialysate from acetate-containing bicarbonate dialysate to acetate-free bicarbonate dialysate, urticaria was clearly less than that seen in previous HD sessions, and subsided after discontinuation of HD. Subsequently, 20mg of oral prednisolone (PSL) was administered 1h before starting HD, and the patient did not experience general pruritus, urticaria, or dyspnea after starting the session. When administered acetate-containing bicarbonate dialysate after oral PSL pretreatment, the patient again experienced general pruritus, urticaria and dyspnea. Few reports have been published on the occurrence of anaphylactoid reactions during HD using acetate dialysate. We report a rare case of anaphylactoid reactions with acetate in acetate-containing bicarbonate dialysate that were reduced with the use of acetate-free bicarbonate dialysate and oral PSL pretreatment.

Comparison between Acetate versus Bicarbonate dialysate during Hemodialysis among Acute Renal Failure Patients, Assuit University hospital

Critically ill patients with acute renal failure who are receiving dialysis therapy may suffer from many complications that can be decreased by using bicarbonate dialysate during dialysis sessions. Aim: this study was carried out to compare between the hemodialized acute renal failure patientsusing bicarbonate versus acetate dialysate ondeveloping complications. Design: descriptive comparative designutilized in this study. Setting: This study was carried out at the kidney dialysisunit, Assiut University Hospital. Subjects Sixty adult male and female critically ill patients with acute renal failure who are admitted to the kidney dialysis unit (how many using bicarbonate and how many using acetate and how you selected them).Tool:“hemodialysis patient observational and monitoring tool” was used to monitor and record the personal and medical data needed for this study by the researcher.Methods: Interview, observation and reviewing patient`s records were utilized to collect data pertinent to the study. Each patient was monitored closely ten minutes before connection to the dialysis machine, during the dialysis session and ten minutes after disconnection, three times per week for two successive weeks. Results: The patients on the acetate group had experienced many problems (tachycardia, hypotension and dyspnea). There was a significant statistical difference between both groups with (p value=0.001). Conclusion: the group of patients on bicarbonate dialysate during dialysis sessions was found to experience lesser problems than acetate dialysis group.

Approach to the Hemodialysis Patient With an Abnormal Serum Bicarbonate Concentration

We present a patient receiving hemodialysis with a persistently high serum bicarbonate concentration to illustrate the evaluation and management issues for patients with both high (>25 mEq/L) and low (<20 mEq/L) pretreatment values. Patients with high serum bicarbonate concentrations typically are malnourished and have low rates of endogenous acid production. Evaluation should begin with assessment of whether an acute and potentially reversible cause of metabolic alkalosis is present. If not, management should be directed at treating malnutrition. By contrast, patients with low predialysis serum bicarbonate concentrations, in the absence of an acute and reversible cause, may benefit from increasing the level by an adjustment in dialysate bicarbonate concentration. However, the level at which one should intervene and to what extent serum bicarbonate concentration should be increased are unresolved issues. Whether such an intervention will reduce mortality risk has not been determined.

Comparison of Sustained Low‐Efficiency Dialysis With Acetate‐Free and Acetate‐Containing Bicarbonate Dialysate in Unstable Patients

This work is focused on the problem of maintenance of intradialytic hemodynamic safety in unstable patients with acute kidney injury (AKI). A hypothesis that "small" quantities of acetate in standard bicarbonate dialysate can cause pronounced acetatemia and exacerbate cardiovascular instability was tested. In this prospective randomized study, a group of patients with AKI after cardiac surgery was treated with sustained low-efficiency dialysis with either acetate-containing bicarbonate dialysate or acetate-free dialysate, where acetate is replaced by hydrochloric acid. It was demonstrated that application of acetate-containing bicarbonate dialysate results in blood acetate levels up to 12 times the normal level. Additionally, it is associated with a 3.8-fold-increased risk of hemodynamic complications in comparison with acetate-free dialysate. The choice of acetate-free or acetate-containing bicarbonate dialysate does not influence adequacy of correction of the acid-base and electrolyte content of blood.

Hemodialysis: Core Curriculum 2014

From the Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN. Received May 1, 2013. Accepted in revised form July 1, 2013. Originally published online November 21, 2013. Address correspondence to Thomas A. Golper, MD, S3303 Medical Center North, Vanderbilt University Medical Center, 21st Ave S, Nashville, TN 37232. E-mail: thomas.golper@vanderbilt. edu 2013 by the National Kidney Foundation, Inc. 0272-6386/$36.00 http://dx.doi.org/10.1053/j.ajkd.2013.07.028 PRINCIPLES OF DIALYSIS AND HOW MODALITIES DIFFER

A step towards optimal dialysate bicarbonate concentration

The optimal dialysate bicarbonate concentration is one that prevents acidosis at the beginning of the next dialysis session while avoiding postdialysis alkalosis. Few studies have assessed the effect of different dialysate bicarbonate levels on patient outcomes, but Tentori et al. now report that high dialysate bicarbonate concentrations may contribute to adverse outcomes.

Association of Dialysate Bicarbonate Concentration With Mortality in the Dialysis Outcomes and Practice Patterns Study (DOPPS)

Most hemodialysis patients worldwide are treated with bicarbonate dialysis using sodium bicarbonate as the base. Few studies have assessed outcomes of patients treated with different dialysate bicarbonate levels, and the optimal concentration remains uncertain. The Dialysis Outcomes and Practice Patterns Study (DOPPS) is an international prospective cohort study. This study included 17,031 patients receiving thrice-weekly in-center hemodialysis from 11 DOPPS countries (2002-2011). Dialysate bicarbonate concentration. All-cause and cause-specific mortality and first hospitalization, using Cox regression to estimate the effects of dialysate bicarbonate concentration, adjusting for potential confounders. Demographics, comorbid conditions, laboratory values, and prescriptions were abstracted from medical records. Mean dialysate bicarbonate concentration was 35.5 ± 2.7 (SD) mEq/L, ranging from 32.2 ± 2.3 mEq/L in Germany to 37.0 ± 2.6 mEq/L in the United States. Prescription of high dialysate bicarbonate concentration (≥38 mEq/L) was most common in the United States (45% of patients). Approximately 50% of DOPPS facilities used a single dialysate bicarbonate concentration. 3,913 patients (23%) died during follow-up. Dialysate bicarbonate concentration was associated positively with mortality (adjusted HR, 1.08 per 4 mEq/L higher [95% CI, 1.01-1.15]; HR for dialysate bicarbonate ≥38 vs 33-37 mEq/L, 1.07 [95% CI, 0.97-1.19]). Results were consistent across levels of pre-dialysis session serum bicarbonate and between facilities that used a single dialysate bicarbonate concentration and those that prescribed different concentrations to individual patients. The association of dialysis bicarbonate concentration with mortality was stronger in patients with longer dialysis vintage. Due to the observational nature of the present study, we cannot rule out that the reported associations may be biased by unmeasured confounders. High dialysate bicarbonate concentrations, especially prolonged exposure, may contribute to adverse outcomes, likely through the development of postdialysis metabolic alkalosis. Additional studies are warranted to identify the optimal dialysate bicarbonate concentration.

Correlation ofhemochromatosisgene mutations and cardiovascular disease in hemodialysis patients

BACKGROUND AND OBJECTIVESCardiovascular disease (CVD) is a major cause of death in hemodialysis (HD) patients. Hemochromatosis (HFE) gene mutations are reported to be associated with CVD. The present study aims to investigate the association of HFE gene polymorphism with CVD in HD patients.DESIGN AND SETTINGSCross-sectional case-control.METHODSC282Y/H63D mutations of HFE gene were evaluated in 560 HD patients and 480 healthy controls from 4 HD centers in North China. The results obtained from this evaluation process were correlated with biochemical parameters including iron status (serum iron, ferritin, and transferrin concentration), cardiovascular disease, and inflammation marker CRP, IL-6, TNF-α.RESULTSNo C282Y mutations were detected in HD patients or healthy controls in this study. The genotype of H63D heterozygous mutation was similar in HD patients with CVD, HD patients without CVD, and controls. H63D homozygous mutation was 7.4% (19/257), 3.1% (9/303), and 1.0% (5/480) for the 3 groups, respectively. Compound heterozygosity was not found in this study. The relative risk for CVD in HD patients with H63D homozygous mutation was 2.59 (95% CI: 1.15–5.84). H63D homozygous mutation had significantly higher serum ferritin concentrations compared with wild-type individuals. Moreover, HD patients had significantly higher levels of inflammatory biomarkers such as CRP, IL-6, and TNF-α. The multivariate logistic regression analysis revealed that H63D mutation instead of ferritin level was an independent risk factor of CVD for HD patients.CONCLUSIONSOur study demonstrates for the first time that there was an association between H63D homozygous mutations and CVD in HD patients. Elevated serum CRP, IL-6, and TNF-α levels were also related to CVD in HD patients.

Post‐Dilution on Line Haemodiafiltration with Citrate Dialysate: First Clinical Experience in Chronic Dialysis Patients

Background. Citrate has anticoagulative properties and favorable effects on inflammation, but it has the potential hazards of inducing hypocalcemia. Bicarbonate dialysate (BHD) replacing citrate for acetate is now used in chronic haemodialysis but has never been tested in postdilution online haemodiafiltration (OL-HDF). Methods. Thirteen chronic stable dialysis patients were enrolled in a pilot, short-term study. Patients underwent one week (3 dialysis sessions) of BHD with 0.8 mmol/L citrate dialysate, followed by one week of postdilution high volume OL-HDF with standard bicarbonate dialysate, and one week of high volume OL-HDF with 0.8 mmol/L citrate dialysate. Results. In citrate OL-HDF pretreatment plasma levels of C-reactive protein and β2-microglobulin were significantly reduced; intra-treatment plasma acetate levels increased in the former technique and decreased in the latter. During both citrate techniques (OL-HDF and HD) ionized calcium levels remained stable within the normal range. Conclusions. Should our promising results be confirmed in a long-term study on a wider population, then OL-HDF with citrate dialysate may represent a further step in improving dialysis biocompatibility.

The effect of frequent hemodialysis on nutrition and body composition: Frequent Hemodialysis Network Trial

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight and composition among 245 patients randomized to 6- or 3-times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to 6-times per week nocturnal or 3-times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in pre-dialysis body weight of 1.5 ± 0.2 kg in the 6 times per week group at one month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water decreased in the 6 times per week compared to the 3 per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water or body cell mass. In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in “dry” body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced extracellular water but did not increase serum albumin or body cell mass while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.

Effects of Citrate Acid Concentrate (Citrasate®) on Heparin N Requirements and Hemodialysis Adequacy: A Multicenter, Prospective Noninferiority Trial

Background: Citrasate®, citric acid dialysate (CD), contains 2.4 mEq of citric acid (citrate), instead of acetic acid (acetate) as in standard bicarbonate dialysate. Previous studies suggest CD may improve dialysis adequacy and decrease heparin requirements, presumably due to nonsystemic anticoagulant effects in the dialyzer. Methods: We prospectively evaluated 277 hemodialysis patients in eight outpatient facilities to determine if CD with reduced heparin N (HN) would maintain dialyzer clearance. Subjects progressed through four study periods [baseline (B): bicarbonate dialysate + 100% HN; period 1 (P1): CD + 100% HN; period 2 (P2): CD + 80% HN; period 3 (P3): CD + 66.7% HN]. The predefined primary endpoint was noninferiority (margin –8%) of the percent change in mean dialyzer conductivity clearance between baseline and P2. Results: Subjects were 57.4% male, 41.7% white, 54.3% black, and 44.4% diabetic; mean age was 59 ± 14.4 years; mean time on dialysis was 1,498 ± 1,165 days; 65.7% had arteriovenous fistula, 19.9% arteriovenous graft, 14.4% catheters, and 27.8% used antiplatelet agents. Mean dialyzer clearance increased 0.9% (P1), 1.0% (P2), and 0.9% (P3) with CD despite heparin reduction. SpKt/V remained stable (B: 1.54 ± 0.29; P1: 1.54 ± 0.28; P2: 1.55 ± 0.27; P3: 1.54 ± 0.26). There was no significant difference in dialyzer/dialysis line thrombosis, post-HD time to hemostasis, percent of subjects with adverse events (AEs), or study-related AEs. Conclusions: CD was safe, effective, and met all study endpoints. Dialyzer clearance increased approximately 1% with CD despite 20–33% heparin reduction. Over 92% of P3 subjects demonstrated noninferiority of dialyzer clearance with CD and 33% HN reduction. There was no significant difference in dialyzer clotting, bleeding, or adverse events.