Hemodiafiltration Using Dialysate as Substitution Fluid

To reduce the cost of hemodiafiltration (HDF), a standard hemodialysis machine was modified to permit in-line production of substitution fluid from bicarbonate dialysate. The authors' present data showing that this procedure was made bacteriologically safe; was simple to use, and offered a cheap approach to perform high-flux HDF using a hemodifilter of relatively small membrane surface area.     

An Economical New Process for Incenter Bicarbonate Dialysate Production: Comparison with Acetate in a Large Dialysis Population

It is generally agreed that bicarbonate dialysate is preferable to acetate dialysate, but the major limiting factors of high cost and technical difficulty in maintaining its stability for prolonged periods preclude its widespread use. The procedure developed by the authors stabilizes bicarbonate dialysate for up to 4 days, rendering bicarbonate dialysate feasible for routine out-patient use. HCO3 dialysate is produced in our dialysis unit after an initial investment of $10,000.00, at a cost per 4-h treatment of $1.22 at a dialysate flow of 500 cc/min. One hundred fifty-one chronic dialysis patients participated in an 18-week study to evaluate clinical symptomatology when bicarbonate was substituted for acetate as the dialysis base buffer. Evaluation of each dialysis treatment (total of 8,183 treatments) consisted of both subjective and objective criteria (vomiting, angina, cramps, hypotension, and frequency of use of mannitol, hypertonic saline, and nitroglycerine). The patients were unaware of the change in dialysate solutions. There was a significant reduction (p less than 0.001) in the incidence of vomiting, cramps, hypotension, nausea, flushing, and the use of mannitol and hypertonic saline during bicarbonate dialysate treatment compared with acetate dialysate. Shortness of breath, angina, mental confusion, and paresthesias were not statistically changed. Although the method of HCO3 dialysate production is associated with occasional higher bacterial count than currently recommended by AAMI standards, no adverse reactions were observed in patients treated with standard efficiency dialyzers. It is concluded that the process for incenter HCO3 production is safe, economical, and better tolerated than acetate dialysate.     

Errors in the Selection of Dialysate Concentrates Cause Severe Metabolic Acidosis During Bicarbonate Hemodialysis

Abstract: Severe metabolic acidosis occurred during bicarbonate hemodialysis as the result of an error made in the selection of the dialysate concentrate. We questioned whether or not it was possible for the dialysis equipment to regulate the proportions in the dialysate fluid using an incorrect dialysate concentrate and still obtain the proper conductivity. We simulated this situation in vitro and found that during bicarbonate dialysis an inappropriately acidic dialysate fluid could replace the normal dialysate with an adequate range of conductivity still being maintained and therefore no triggering of alarms. The investigation showed that the dialysis machines were not adequately adjusted for sensitivity to the concentrates being employed during dialysis. We concluded that dialysis equipment should be fitted with on-line pH meters with alarm systems.     

Increment in Dialysate Sodium with Sodium Chloride or Bicarbonate Addition

Abstract: Hemodialysis was performed in 12 patients for 2 weeks each utilizing acetate dialysate containing 134 mEq/L sodium and dialysate containing 143 mEq/L sodium, achieved by the addition of sodium chloride or sodium bicarbonate to the acetate dialysate. Intradialytic morbidity was lower, dialysis hypoxemia less marked, and predialysis blood pH higher with the bicarbonate-than with the chloride-added dialysate. The long-term use of sodium bicarbonate-added dialysate in three patients was safe. Dialysate pH adjustment was not required. These findings suggest that the addition of sodium bicarbonate (50–75 g) to acetate dialysate may be preferred to sodium chloride for increasing dialysate sodium in selected patients.     

Acetate-Free Biofiltration: A Viable Alternative to Bicarbonate Dialysis

Eight patients were studied during four sessions of acetate-free biofiltration (AFBF). AFBF is a new dialysis technique with no base replacement agents in the dialysate and with the addition in postdilution mode of bicarbonate (HCO3) solution directly into the extracorporeal blood circuit. In this study the effects on acid-base balance of different infusions of sodium bicarbonate (NaHCO3) ranging from 751 to 1,002 mEq per session was evaluated. There were significant positive correlations between the HCO3 infused and net HCO3 gained (r = 0.776, p less than 0.0001) and between HCO3 infused and plasma intratreatment HCO3 changes (n = 0.562, p less than 0.001). Stepwise multiple linear regression analysis demonstrated that HCO3 infused and plasma predialysis HCO3 values played the major role in HCO3 balance in AFBF. The best correction of metabolic acidosis was obtained with the infusion of 900-1,000 mEq of HCO3. The use of substitution fluid with 145 mEq/L of Na concentration avoids the risk of a positive intratreatment Na balance.     

Pancreatitis Causes Brownish-Black Peritoneal Dialysate Due to the Presence of Methaemalbumin

Two patients treated with continuous ambulatory peritoneal dialysishad striking brownish-black coloured peritoneal dialysate concomitantwith underlying pancreatitis. Examination of the second patient'sdialysate by recording spectrophotometry showed the discolorationto be due to methaemalbumin. Haemorrhagic pancreatitis, by releasingproteolytic enzymes and perhaps by using the lesser sac as ananatomical cul-de-sac for chemical reaction, provides a suitablemilieu for the production of methaemalbumin from red blood cellsin dialysate.     

Proteomic Analysis of Peritoneal Dialysate Fluid in Patients with Dialysis-Related Peritonitis

The prognosis of uremia patients on continuous ambulatory peritoneal dialysis (CAPD) is related to frequent peritonitis rate. Frequent peritonitis will lead to peritoneum failure, making CAPD unfeasible. We have performed proteomic profiling of peritoneal dialysis effluent samples from a cross-section of CAPD patients with and without peritonitis in order to identify biomarkers of peritonitis. We performed 2D gel electrophoresis and surface-enhanced laser esorption/ionization time of flight mass spectrometry (SELDI-TOF MS) on peritoneal dialysis effluent from 16 subjects with peritonitis. A genetic algorithm search of principal component space revealed a group of a peak distinguishing peritonitis-positive subjects, with mass/charge (m/z) values of 11,117.4. Our analyses identified the peak at m/z 11,117.4 with an accuracy of 95% for classifying peritonitis. Mass spectrometric analysis of peritonitis PDE samples identified the 11,117.4 protein as β2-microglobulin (B2M). Using an unbiased protein profiling approach, we have validated previously reported findings of B2M as a biomarker associated with CAPD peritonitis. Prospective studies are warranted to establish additional biomarkers that would be predictive of peritoneal dialysis peritonitis. Besides, extending the study to a larger number of patients with subgroup analyses may yield additional information of the peritoneal dialysate proteins in association with dialysis adequacy, residual renal function, nutritional status, and risk of peritoneal infection.     

Continuous Computerized Monitoring of Hemodynamic Parameters during Acetate Dialysis, Bicarbonate Dialysis, and Acetate-Free Biofiltration

The effects of continuous, computerized, non-invasive hemodynamic monitoring on the appearance of intradialytic symptoms, aided by preventive therapeutic maneuvers, were evaluated in 30 critically ill patients undergoing regular acetate dialysis. The hemodynamic behavior was assessed by a system that interfaces a personal computer with a blood pressure monitor and to a transthoracic electrical impedance-measuring instrument. Monitoring allowed us to reduce significantly the frequency of some important intradialytic symptoms such as nausea, vomiting, and hypotension. The same monitoring system was used acutely to characterize differing hemodynamic behaviors during acetate dialysis (AD), bicarbonate dialysis (BD), and acetate-free biofiltration (AFBF). AD showed a prevalent vasodilation effect with a compensatory increase in heart rate and higher cardiac output values, which were not sufficient to maintain blood pressure stability. BD and AFBF were characterized by a more efficient vasoconstrictor effect and good hemodynamic stability. AFBF, despite a 1 h reduction in session length compared to BD, did not present significant differences in hemodynamic response resulting from session shortness or other technical changes.     

Machine-generated bicarbonate dialysate for continuous therapy: a prospective, observational cohort study.

BACKGROUND: In 1995, we described the technique of adapting a haemodialysis (HD) machine to produce a composition-adjustable, bicarbonate-based fluid (as our primary source for dialysate) for continuous HD in intensive care unit (ICU) patients with acute renal failure (ARF). The following studies the clinical effects, biochemical changes and economic costs of this practice in a large cohort of patients at a single centre over the last 10 years. METHODS: The CCF-ARF Support Registry (1995-2001) was used to identify 405 patients initially supported with bicarbonate continuous HD. The registry is a prospective, observational cohort database that captures demographic, dialysis therapy, laboratory and outcome data. All supported ARF patients were recorded from 1995-98, and then one in five patients from 1999 to 2001. We also reviewed records of the individual dialysis procedures, dialysate disposal, dialysate monitoring tests and specific costs. RESULTS: Continuous HD was performed for 1292 +/- 587 days from 1994 to 2004. Demographics [age 59.57 +/- 14.41 years, weight 84.2 +/- 24 kg, male 65%, chronic kidney disease (CKD) 34%] and ICU mortality (60.5%) were comparable to other reported series. Day 4 solute [BUN 52.3 mg/dl (95% CI 49.6-54.9), creatinine 2.79 mg/dl (95% CI 2.64-2.95)], electrolyte and acid-base balance [bicarbonate 24.12 mmol/l (95% CI 23.7-24.6)] were well controlled. Dialysate monitoring revealed no positive cultures or elevated endotoxin levels. Variable-composition dialysate was achieved and delivered to all patients without adverse consequences. The cost of dialysate actually declined over time (1995 = $0.91/l, 2005 = $0.67/l). CONCLUSION: We have demonstrated that ICU ARF patients can be safely, effectively and economically supported with continuous HD using this source.     

Better correction of metabolic acidosis, blood pressure control, and phagocytosis with bicarbonate compared to lactate solution in acute peritoneal dialysis

Lactate solution has been the standard dialysate fluid for a long time. However, it tends to convert back into lactic acid in poor tissue-perfusion states. The aim of this study was to evaluate the efficacy of magnesium (Mg)- and calcium (Ca)-free bicarbonate solution compared with lactate solution in acute peritoneal dialysis (PD). Renal failure patients who were indicated for dialysis and needed acute PD were classified as shock and nonshock groups, and then were randomized to receive either bicarbonate or lactate solution. Twenty patients were enrolled in this study (5 in each subgroup). In the shock group, there were more rapid improvements and significantly higher levels of blood pH (7.40 +/- 0.04 versus 7.28 +/- 0.05, p < 0.05), serum bicarbonate (23.30 +/- 1.46 versus 18.37 +/- 1.25 mmol/L, p < 0.05), systolic pressure (106.80 +/- 3.68 versus 97.44 +/- 3.94 mm Hg, p < 0.05), mean arterial pressure (80.72 +/- 2.01 versus 73.28 +/- 2.41 mm Hg, p < 0.05), percentages of phagocytosis of circulating leukocytes (65.85% +/- 2.22 versus 52.12% +/- 2.71, p < 0.05), and percentages of positive nitroblue tetrazolium (NBT) reduction test without and with stimulation (14.43 +/- 1.93 versus 9.43 +/- 2.12, p < 0.05 and 65.08 +/- 6.80 versus 50.23 +/- 4.21, p < 0.05, respectively) in the bicarbonate subgroup compared with the lactate subgroup. In the nonshock group, blood pH, serum bicarbonate, and phagocytosis assays in both subgroups were comparable. Lactic acidosis was more rapidly recovered and was significantly lower with bicarbonate solution for both shock and nonshock groups (3.63 +/- 0.37 versus 5.21 +/- 0.30 mmol/L, p < 0.05 and 2.92 +/- 0.40 versus 3.44 +/- 0.34 mmol/L, p < 0.05, respectively). Peritoneal urea and creatinine clearances in both subgroups were comparable for both shock and nonshock groups. There was no peritonitis observed during the study. Serum Mg and Ca levels in the bicarbonate subgroup were significantly lower, but no clinical and electrocardiographic abnormality were observed. We concluded that Mg- and Ca-free bicarbonate solution could be safely used and had better outcomes in correction of metabolic acidosis, blood pressure control, and nonspecific systemic host defense with comparable efficacy when compared to lactate solution. It should be the dialysate of choice for acute PD especially in the poor tissue-perfusion states such as shock, lactic acidosis, and multiple organ failure.     

Effect of Bicarbonate-Containing Dialysate on Chronic Hemodialysis Patients: A Comparative Study

Changes in pH and blood gases were studied during hemodialysis with both acetate and bicarbonate dialysates. During acetate dialysis, Pao₂ and Paco₂ decreased significantly (P < 0.05) from 101 ± 2 to 93 ± 3 mmHg and from 34.4 ± 1.0 to 31.8 ± 0.9 mmHg, respectively, whereas during bicarbonate dialysis neither parameter changed significantly. The final pH was 7.45 ± 0.01 during acetate dialysis and 7.50 ± 0.02 during bicarbonate dialysis. Plasma bicarbonate rose immediately and progressively from 18.9 ± 0.8 to 26.8 ± 0.9 mmol/L with bicarbonate dialysis, whereas the increase was moderate, from 19.6 ± 0.6 to 22.3 ± 0.5 mmol/L, with acetate dialysis. These data indicate that dialysis-induced hypoxemia was prevented and correction of acidosis was more adequate with bicarbonate dialysis. During a two-year period on bicarbonate dialysis, total cholesterol, HDL-cholesterol, and triglycerides did not change significantly when compared to acetate dialysis. The most striking change was the increased tolerance to dialysis with bicarbonate dialysis, which included a 50% reduction in hypotensive episodes and muscle cramps and an almost complete absence of headache, nausea, and vomiting.     

An unsuspected cause for metabolic acidosis in chronic renal failure: sorbent system hemodialysis

A severe metabolic acidosis was produced in a patient with chronic renal failure by hemodialysis using a sorbent system to regenerate bicarbonate dialysate with an initial bicarbonate concentration of 60 mEq/L. The acidosis resolved with standard single-pass hemodialysis. In five additional patients, the bicarbonate concentration of the dialysate with the sorbent system was noted to be low and quite variable (mean +/- SD, 16.5 +/- 8.3 mEq/L, range 5 mEq/L to 39 mEq/L). The low dialysate bicarbonate failed to correct metabolic acidosis and, in fact, was capable of further lowering the serum bicarbonate. The capacity of the regenerating cartridge to release protons makes this form of dialysis a potential cause for metabolic acidosis. The safety of the sorbent system dialysis, at least in the bicarbonate mode, requires further evaluation.     

Dialysate to plasma solute concentration (D/P) versus peritoneal transport parameters in CAPD

The relationship between dialysate to plasma solute equilibrationratio (D/P) and diffusive (diffusive mass transport coefficients,K_BD) as well as convective (sieving coefficient, S, and netultrafiltration) transport characteristics were studied in clinicallystable CAPD patients and in patients with loss of ultrafiltrationcapacity (UFC). Forty-one 6-h single-dwell studies with standardglucose-based dialysis fluids containing 1.36/ (n = 9), 2.27%(n = 9), and 3.86% (n = 23) anhydrous glucose were carried outin 33 clinically stable CAPD patients. Eleven patients withloss of UFC were studied with 3.86% glucose solution. Intraperitonealdialysate volumes were calculated from the dilution of the tracer(¹³¹I-albumin) with a correction applied for its eliminationfrom the peritoneal cavity. K_BD and S were estimated using thePyle-Popovich-Moncrief model with aqueous plasma concentrations.A theoretical D/P curve was derived with and without takingconvective transport and peritoneal reabsorption into account. The three different glucose solutions yielded D/P curves whichwere similar for urea and potassium. For creatinine a slowerequilibration and for glucose and sodium a faster decrease indialysate concentration were observed with more hypertonic solutions.In general, there was a strong correlation which was best at240 min between D/P (for glucose dialysate/initial dialysateconcentration, D/D_o) and K_BD for all solutes (except sodium),whereas the correlation between D/P and convective transportparameters was much weaker. K_BD for creatinine (with 3.86% glucosesolution) could be estimated (r=0.98) from aqueous D/P usingthe experimental formula: creatinine K_BD= –1.8–In(1–D_24O/P)/0.1. Patients with loss of UFC due to increaseddiffusive transport (n = 8) could be discriminated from theclinically stable patients using K_BD and D/P (or D/Do) for creatinineand glucose or D/P for sodium. However, patients with loss ofUFC associated with increased peritoneal reabsorption (n = 2)could not be identified using these parameters. Theoreticallyderived D/P curves were in excellent agreement with measuredD/P for 1.36% glucose solution and simulations were satisfactoryalso for the 2.27% and 3.86% solutions provided that the effectof convective transport was taken into account. The standardized peritoneal equilibration test (PET) as proposedby Twardowski et al. [17] seems to be appropriately designedas regards duration of the dwell and the choice of glucose andcreatinine as investigated solutes. Thus, PET can be recommendedas a sensitive routine investigation for the monitoring of normal/abnormalperitoneal transport behaviour in peritoneal dialysis patients.     

Calcium Carbonate Precipitation in Bicarbonate Hemodialysis

Calcium carbonate has been observed to precipitate in the fluid pathway of dialysate delivery systems dispensing bicarbonate-containing dialysates. Such precipitation can occlude the fluid pathway, leading to system malfunction and increased maintenance requirements. We show that commercial supplies of sodium bicarbonate are contaminated by trace amounts of sodium carbonate. This contamination may result in immediate precipitation of calcium carbonate on formulation of the dialysate, since bicarbonate-containing dialysates, as formulated, are metastable with respect to calcium carbonate. Sparging of the bicarbonate-containing concentrate with carbon dioxide converts any carbonate to bicarbonate, thus avoiding the formation of precipitates on addition of calcium ions.     

The faster potassium-lowering effect of high dialysate bicarbonate concentrations in chronic haemodialysis patients.

BACKGROUND: Hyperkalaemia is common in patients with advanced renal disease. In this double-blind, randomized, three-sequence, crossover study, we compared the effect of three dialysate bicarbonate concentrations ([HCO3-]) on the kinetics of serum potassium (K+) reduction during a conventional haemodialysis (HD) session in chronic HD patients. METHODS: We studied eight stable HD patients. The choice of dialysate [HCO3-] followed a previously assigned treatment protocol and the [HCO3-] used were low bicarbonate (LB; 27 mmol/l), standard bicarbonate (SB; 35 mmol/l) and high bicarbonate (HB; 39 mmol/l). Polysulphone dialysers and automated machines provided blood flow rates of 300 ml/min and dialysis flow rates of 500 ml/min for each HD session. Blood samples were drawn at 0 (baseline), 15, 30, 60 and 240 min from the arterial extracorporeal line to assess blood gases and serum electrolytes. In three of the eight patients, we measured serum K+ 1 h post-dialysis as well as K+ removal by the dialysis. The same procedures were followed until the completion of the three arms of the study, with a 1 week interval between each experimental arm. RESULTS: Serum K+ decreased from 5.4+/-0.26 (baseline) to 4.96+/-0.20, 4.90+/-0.19, 4.68+/-0.13 and 4.24+/-0.15 mmol/l at 15, 30, 60 and 240 min, respectively, with LB; from 5.38+/-0.21 to 5.01+/-0.23, 4.70+/-0.25, 4.3+/-0.15 and 3.8+/-0.19 mmol/l, respectively, with SB; and from 5.45+/-0.25 to 4.79+/-0.17, 4.48+/-0.17, 3.86+/-0.16 and 3.34+/-0.11 mmol/l, respectively, with HB (P<0.05 for high vs standard and low [HCO3-] at 60 and 240 min). The decrease in serum K+ correlated with the rise in serum [HCO3-] in all but LB (P<0.05). Potassium rebound was 3.9+/-10.2%, 5.2+/-6.6% and 8.9+/-4.9% for LB, SB and HB dialysates, respectively (P=NS), while total K+ removal (mmol/dialysis) was 116.4+/-21.6 for LB, 73.2+/-12.8 for SB and 80.9+/-15.4 for HB (P=NS). CONCLUSIONS: High dialysate [HCO3-] was associated with a faster decrease in serum K+. Our results strongly suggest that this reduction was due to the enhanced shifting of K+ from the extracellular to the intracellular fluid compartment rather than its removal by dialysis. This finding could have an impact for those patients with life-threatening pre-HD hyperkalaemia.     

The Renin-Angiotensin-Aldosterone System During Haemodialysis With Acetate or Bicarbonate at Different Dialysate Sodium Concentrations

The hormones of the renin–angiotensin–aldosteronesystem were measured during regular haemodialysis with acetateor bicarbonate at dialysate sodium concentrations of 135, 140,145, and 150 mmol/l. Plasma renin activity and aldosterone concentrationwere higher during acetate haemodialysis than during bicarbonatehaemodialysis. At lower dialysate sodium concentrations, plasmarenin activity (acetate dialysis and bicarbonate dialysis) andaldosterone concentration (only acetate dialysis) were higherthan they were at higher dialysate sodium concentrations. Plasmarenin activity increased during acetate dialysis, but did notchange during bicarbonate dialysis. Aldosterone and potassiumconcentrations were positively correlated. Aldosterone decreasedduring haemodialysis (increase to predialysis values at theend of haemodialysis (4 h) at lower dialysate sodium concentrations).It is concluded that the renin-angiotensin-aldosterone systemis activated more during acetate dialysis than during bicarbonatedialysis. Aldosterone concentrations seem to be related moreclosely to serum potassium than to renin–angiotensin–aldosteronesystem and to serum sodium intradialytically.     

Long-Term Effect of Different Dialysate Calcium Concentrations on Parathyroid Hormone Levels in Hemodialysis Patients

The appropriate dialysate calcium concentration (D[Ca]) for hemodialysis (HD) therapy has not yet reached a consensus. We have conducted a prospective control study for five years on the effects of different D[Ca] on serum intact parathyroid hormone (iPTH) levels. Patients were divided into three groups receiving different D[Ca] therapies: the low-Ca (D[Ca]?=?2.5 mEq/L; N?=?96), mid-Ca (D[Ca]?=?3.0 mEq/L; N?=?121), and high-Ca (D[Ca]?=?3.5 mEq/L; N?=?82) groups. After five years' study, only 41 patients in the low-Ca group, 34 in the mid-Ca group, and 32 in the high-Ca group completed the study. The results demonstrated that serum corrected calcium concentrations were significantly lower in the low-Ca group compared with other groups in years 3 and 4, although the products of corrected calcium time phosphate did not show difference between each group.^Δserum alkaline phosphatase (^ΔAlk-p) to baseline levels increased significantly after the fourth year in all three groups (p < 0.05). Serum ^Δ iPTH only increased significantly after the fourth year in the low-Ca group (p < 0.05) but not in the other groups. There were no significant differences in the extent of ^ΔAlk-p and ^ΔiPTH between the groups. Cox proportional methods also showed no difference in cumulative survival between the groups. In conclusion, our results demonstrate that compared with the other two groups of D[Ca], long-term use of D[Ca] of 2.5 mEq/L was associated with relatively lower serum calcium concentration. Perhaps this was related to a greater extent of iPTH concentration elevation after five years.     

Relationship between interdialytic weight gain and acid-base status in hemodialysis by bicarbonate

The aim of this study was to determine the relationship between interdialytic weight gain and acid-base balance pre- and posthemodialysis in uremic patients undergoing hemodialysis with a high bicarbonate dialysate (39 mmol/L). To this end we studied 8 stable uremic patients on regular hemodialysis thrice weekly who had stable hematocrit values for at least 3 months, similar clinical characteristics including dry weight but widely varying interdialytic weight gain. Arterial line blood samples were collected anaerobically in heparinized syringes pre- and posthemodialysis in 4 consecutive hemodialysis sessions for the determination of pH, Paco2, and HCO3. Prehemodialysis values (mean +/- SD) were pH = 7.34 +/- 0.03, Paco2 = 36.43 +/- 1.4, and Hco3 = 20.1 +/- 1.55. Posthemodialysis values were pH= 7.47 +/- 0.02, Paco2 = 38.72 +/- 2.0, and HCO3 = 27.73 +/- 1.72. In other words, patients were moderately acidemic prior to and moderately alkalemic after the hemodialysis session. Of note, a significant negative correlation was revealed between the interdialytic weight gain and the values of prehemodialysis blood pH (r = -0.721, p < 0.001) and HCO3 (r = -0.836, p < 0.001) and posthemodialysis pH (r = -0.533, p < 0.001), Paco2 (r = -0.623, p < 0.001) and HCO3 (r = -0.815, p < 0.001), suggesting an important role of the interdialytic weight gain on acid-base equilibrium of uremic patients undergoing hemodialysis. Thus, patients with high interdialytic weight gains may require higher bicarbonate concentrations to achieve normal acid-base status whereas patients with low interdialyic weight gains may require lower bicarbonate concentrations to prevent alkalemia at the end of dialysis.