Use of lactate as a base in hemodialysis

The purpose of our study was to investigate the feasibility of using lactate as a complete or partial substitute for acetate in hemodialysis solutions. Six patients, each serving as his own control, were dialyzed once against a dialysis solution containing 40 mM acetate, once against a dialysis solution containing 40 mM DL-lactate and once against a dialysis solution containing 20 mM each of acetate and DL-lactate. Six additional patients underwent hemodialysis using acetate + lactate for a 3-week period, and the blood acid-base values during this period were compared to those obtained during periods when acetate was used. All dialysis treatments were well tolerated without hypotension or other clinical manifestations. When acetate + lactate was used, only a slight delay in the correction of acidosis during dialysis occurred and the net change in the plasma bicarbonate value appeared to be comparable to that measured with acetate. On the other hand, when lactate was used, the increase in the plasma bicarbonate level during and immediately after dialysis was reduced. With acetate + lactate, intradialytic blood D-lactate levels remained between 1 and 2 mM and returned promptly to near baseline within 1 h after dialysis. During 3 weeks of dialysis using acetate + lactate, predialysis plasma bicarbonate values were similar to those achieved when using acetate, but with acetate + lactate, the intradialytic plasma acetate levels were reduced by 50%. The results suggest that DL-lactate merits further evaluation as a potential base for hemodialysis solutions, and that both the D- and the L-lactate isomers are metabolized in maintenance hemodialysis patients.     

Comparative effects of acetate and bicarbonate hemodialysis on left ventricular function

To assess the comparative effects of hemodialysis with acetate versus bicarbonate base on left ventricular systolic function, we performed M-mode echocardiography on 36 patients prior to and immediately following 4-hr maintenance hemodialysis. Patients were initially dialyzed against either sodium acetate or sodium bicarbonate and 1 week later were dialyzed against the alternate base. The mean velocity of circumferential fiber shortening (mean Vcf, circumferences/s) was used to assess left ventricular systolic function. In patients with normal pre-dialysis mean Vcf hemodialysis with acetate produced no significant change in mean Vcf, whereas hemodialysis with bicarbonate produced a significant increase in mean Vcf. In patients with low pre-dialysis mean Vcf hemodialysis with either base produced a significant increase in mean Vcf. Mean Vcf values obtained after hemodialysis with bicarbonate were significantly higher than those obtained after hemodialysis with acetate, both in patients with normal and low pre-hemodialysis mean Vcf. We conclude that hemodialysis with bicarbonate produces a comparatively greater improvement in left ventricular systolic function than hemodialysis with acetate.     

Hypotension during acetate and bicarbonate dialysis in patients with acute renal failure

Bicarbonate dialysate is claimed to be superior to acetate for both chronic and acute hemodialysis. We compared acetate and bicarbonate dialysates in 30 acute renal failure patients during 120 dialyses. 4 patients were diabetic and 2 had liver failure. Patients were dialyzed alternating acetate and bicarbonate dialysate in a double-blind cross-over manner; each patient was his own control. BUN, creatinine, Na+, K+, osmolality, delta osmolality, % ultrafiltration, arterial blood gases, pre, post and lowest dialysis mean arterial blood pressure, dialysis with hypotensive episodes and symptoms of hypotension were recorded. The measurements obtained for each patient during dialyses with acetate and bicarbonate were compared. There was no difference in predialysis chemistries, osmolality or osmolality fall, no change in mean arterial blood pressure or hypotensive episodes and symptoms and ultrafiltration. PCO2 and pH were slightly lower for the acetate group at the 2nd h but not at the end of dialysis. 4 patients had serum acetate determinations, all metabolized acetate normally. These findings contradict recent suggestions that severely ill patients should not be dialyzed against acetate. Since acetate is technically much easier to use and has no clinical drawbacks, it does not need to be replaced with bicarbonate in acute patients. Other factors must be more important than acetate in generating hypotension during acute dialysis.     

Effects of acetate and bicarbonate dialysate in stable chronic dialysis patients

The effects of acetate and bicarbonate dialysate on the biochemical and clinical parameters of 16 stable chronic hemodialysis patients were investigated in a double-blind crossover study. A central delivery system was used for both types of dialysates with identical sodium concentrations (138 mEq/liter) and osmolality in a single-pass dialysate flow. The results indicate that dialysis with bicarbonate leads to significantly less hypoxemia (P less than or equal to 0.001) and hypotensive episodes (P less than or equal to 0.002) than with acetate. Pre- to post-dialysis blood pressure changes were also more marked during acetate dialysis. Older patients with recurrent hypotension on acetate benefit most from bicarbonate dialysate. This group of patients appears to metabolize acetate more slowly and has a significantly lower post-dialysis bicarbonate concentration (P less than or equal to 0.005) than asymptomatic patients during dialysis with acetate dialysate.     

Pathogenesis of Dialysis-Induced Hypoxemia

Patients undergoing hemodialysis with acetate-containing dialysis solutions develop hypoxemia. To determine the cause of the hypoxemia, we studied and compared the ventilatory, gas-exchange and blood-gas responses in chronic renal failure patients undergoing hemodialysis with acetate and bicarbonate dialysis solutions. Seven stable chronic dialysis patients were dialyzed against acetate and bicarbonate solutions in a random order. Dialysis was carried out using a 1.5 m² hollow fiber dialyzer at a blood flow rate of 200 ml/min and a dialysate flow rate of 500 ml/min. During acetate dialysis, Pao₂ fell within 15 minutes from a mean control predialysis concentration of 84 = 6 (SEM) mmHg to a mean of 70 ± 7.5 mmHg (P < 0.05), and remained low throughout the study. Pao₂ did not change significantly during bicarbonate dialysis. Total ventilation fell from a predialysis level of 7.2 ± 0.7 L/ min to 5.7 ± 0.6 L/min within 15 minutes (P < 0.05). Paco₂ was not significantly changed from predialysis levels with either acetate or bicarbonate dialysis. Measurement of blood concentration of CO₂ and bicarbonate across the dialyzer indicated that the total CO₂ loss (as CO₂ and bicarbonate) through the dialyzer was 3 millimoles per minute or the equivalent of approximately 60 ml of CO₂ per minute, i.e., about one third of the patient's metabolic production of CO₂.     

Hemodialysis-induced hypoglycemia in diabetic patients

BACKGROUND: The authors have previously reported asymptomatic hypoglycemia in non-diabetic patients on hemodialysis. The present study was designed to assess the effect of hemodialysis on plasma glucose, glucagon, cortisol and catecholamines in diabetic patients. METHODS: Eighteen diabetic patients with chronic renal failure were hemodialyzed using a glucose-free dialysis fluid. They did not take any medication prior to dialysis and were asked not to eat during the first hour on hemodialysis. Blood and dialysate were sampled at regular intervals during the first hour of dialysis for analysis. RESULTS: Plasma glucose fell below 4.0 mmol/l (72 mg/dl) in 7 of the 18 patients, below 3.5 mmol/l (63 mg/dl) in 3 and below 3.0 mmol/l (54 mg/dl) in one. The lowest recorded value was 2.8 mmol/l (50 mg/dl). The mean glucose loss in the waste dialysate was 9.2 g/h. In none of the group of 7 patients whose plasma glucose fell below 4.0 mmol/l (72 mg/dl) did symptoms of hypoglycemia occur. When 6 patients from this group were subsequently dialyzed with a dialysis fluid containing 5.5 mmol/l (100 mg/dl) glucose, their plasma glucose became stabilized within the fasting reference range. There were no significant hormonal changes during the dialysis or between non-hypoglycemic and hypoglycemic patients. CONCLUSIONS: Patients undergoing hemodialysis may become hypoglycemic and not be aware of it. There is no hormonal imbalance causing the hypoglycemia and the hormonal response to the hypoglycemia is blunted. Patients with an initial plasma glucose of 5.5 mmol/l (100 mg/dl) or less who are hemodialyzed and who do not eat during dialysis may be particularly at risk, especially if they are on insulin or taking glucose-lowering medication. These should be dialyzed with a dialysis fluid containing at least 5.5 mmol/l (100 mg/dl) glucose.     

Effects of acetate during regular hemodialysis

The utilization of acetate and its effects on acid-base balance and on free fatty acid metabolism were investigated during regular hemodialysis (HD). Fourteen patients with chronic renal failure were studied during two successive dialysis treatments for which either acetate or bicarbonate were used as a buffer anion in the dialysate. In the acetate studies the mean plasma acetate concentration in the arterial line rose from 0.16 mM to 4.67 mM, while it rose from 0.17 mM to 0.62 mM during bicarbonate dialysis. There was a linear relationship between acetate utilization and the acetate concentration in the venous line. The increase of the blood pH during bicarbonate HD was due to an immediate increase of HCO3, whereas acetate caused a smaller HCO3 rise and a pronounced fall of the pCO2. The heart rate was higher during acetate than during bicarbonate HD. During both types of dialysis there was a twofold rise of total FFA as well as the individual fatty acids palmitate, palmitoleate, oleate, stearate and linoleate which was of similar magnitude when acetate or bicarbonate were used. The postulated antilipolytic effect of the short-chain fatty acid acetate could not be demonstrated under the circumstances of routine hemodialysis. Pre-dialysis dopamine was elevated in 7 of the 11 patients and remained high during both types of HD; other hormones were normal during acetate and bicarbonate HD.     

Effects of uremia, acetate and bicarbonate dialysis on beta-adrenergic responsiveness as assessed by epinephrine-stimulated adenylate cyclase

This study was designed to evaluate beta-adrenergic responsiveness as assessed by the generation of cyclic AMP after the subcutaneous administration of epinephrine in 31 subjects: normal controls, patients with chronic renal insufficiency, hemodynamically stable patients on chronic acetate dialysis and hemodynamically unstable patients with acetate intolerance on chronic bicarbonate dialysis. As compared with controls, only unstable patients on bicarbonate dialysis presented impaired beta-responsiveness, which, in turn, was acutely reduced only after acetate but not bicarbonate dialysis. Our results show that acetate dialysis impairs the beta-adrenergic responsiveness and that the observed beta-hyporesponsiveness in unstable patients with acetate intolerance may represent part of a broader spectrum of autonomic dysfunction which may develop in some patients on chronic hemodialysis.     

Physiologic approach to dialysis-induced hypoxemia. Effects of dialyzer material and dialysate composition

This study was undertaken to evaluate the effects of membrane-related complement activation and dialysate composition on dialysis-associated hypoxemia. Seven chronic hemodialysis patients were hemodialyzed 3 times sequentially with the following three combinations; Cuprophan membrane with acetate dialysate, polymethylmethacrylate (PMMA) membrane with acetate dialysate, and PMMA membrane with bicarbonate dialysate. During dialysis with acetate dialysate, the pulmonary diffusing capacity (DLco) at 30 min after the start of dialysis was decreased to 88% (p less than 0.01) of the predialysis value with PMMA and to 79% (p less than 0.01) with Cuprophan, and the degree of DLco on PMMA membrane was different from that on Cuprophan (p less than 0.01). The degree of leukopenia with PMMA was less than that with Cuprophan. However, the fall in DLco did not alter the alveolar-arterial O2 tension gradient. Although the changes in transcutaneous PO2 (tcPO2) were not constant in all three combinations, a distinct fall in tcPO2 was observed in the first half of dialysis with acetate dialysate. During dialysis with acetate dialysate but not with bicarbonate, the extracorporeal dialyzer removed an average of 60 ml/min of CO2, and the respiratory quotient dropped from a mean predialysis value of 0.86 to 0.59 (p less than 0.001). The arterial CO2 tension was not significantly changed throughout dialysis, but the alveolar ventilation decreased significantly in proportion to the fall in carbon dioxide output. The arterial tension fell from a control level of 91 +/- 6 to 77 +/- 8 mm Hg (p less than 0.01) in 30 min. It is concluded that, in spite of a fall in DLco, dialysis-induced hypoxemia in this group of patients on maintenance dialysis is caused by CO2 loss via the dialyzer, resulting in reflex hypoventilation.     

Hypoxemia during hemodialysis: a critical review of the facts

The literature describing the fall in PaO2 during dialysis is intensively and critically reviewed. This phenomenon is related to both the type of membrane used (cellulosic v noncellulosic membrane), and to the composition of the dialysate (acetate v bicarbonate). It appears that a ventilation/perfusion mismatch due to pulmonary leukostasis can, in part, explain hypoxemia in patients dialyzed with cellulosic membranes. This phenomenon is especially apparent in patients with preexisting pulmonary abnormalities. However, hypoventilation remains the major cause of hypoxemia. This hypoventilation is mainly due to CO2 consumption during acetate metabolism (acetate dialysis), or alkalinization of the blood (bicarbonate dialysis). The metabolic consequences of acetate metabolism, and of bicarbonate and CO2 losses through the dialyzer are critically analyzed. The cause for the increment in oxygen consumption during acetate dialysis is examined. Finally, the respective role of these combined factors are described and used to explain the changes in VCO2, VO2, respiratory quotient (RQ), and PaO2 reported in the literature during dialysis against acetate and/or bicarbonate.     

Hemodialysate composition and intradialytic metabolic, acid-base and potassium changes

We compared the effects of dialysate composition on changes in intermediary metabolites, acid-base balance, and potassium removal during hemodialysis. Patients were dialyzed against dialysates containing acetate or bicarbonate, each with or without glucose, in a four-way cross-over study. Dialysates containing acetate were associated with significant perturbations in intermediary metabolism, including increases in blood citrate, acetoacetate and beta-hydroxybutyrate and a decrease in pyruvate. In contrast, bicarbonate-containing dialysates caused minimal perturbations in intermediary metabolism. Addition of glucose to the dialysate decreased the changes in intermediary metabolites; however, the magnitude of this effect was less than that observed for the change from acetate to bicarbonate. Use of acetate also resulted in lower post-dialysis blood-concentrations of base equivalents than obtained with bicarbonate; this difference was unaffected by the presence or absence of glucose. Although pre- and post-dialysis potassium concentrations were unaffected by the dialysate formulation, total potassium removal was significantly greater when glucose was omitted from the dialysate. Our results suggest that both bicarbonate and glucose should be included in the dialysate, particularly for those patients whose capacity for metabolism may be limited because of highly efficient dialysis, intercurrent illness, or starvation. However, addition of glucose to the dialysate may require a reduction in dialysate potassium to maintain proper potassium homeostasis.     

Adverse ocular effects of acetate hemodialysis

In order to better define ocular dynamics during hemodialysis, we studied intraocular pressure (IOP) and anterior chamber depth (ACD) serially during both acetate and bicarbonate hemodialysis in 10 stable hemodialysis patients. IOP did not change significantly in any patient during dialysis. In contrast, however, ACD decreased significantly during acetate but not bicarbonate dialysis. ACD could be maintained during acetate dialysis by concomitant administration of mannitol. We conclude that acetate dialysis might adversely affect ocular dynamics in susceptible patients with glaucoma or recent ocular surgery. In such individuals administration of mannitol or use of a bicarbonate dialysate should be considered.     

Malignancy Prevalence in the Dialyzed Population and in Waitlisted Potential Kidney Transplant Recipients

Malignancy is the second cause of death in the dialyzed population. However, data on the prevalence of cancer are very scarce. Kidney transplantation improves quality of life, prolongs survival, and is cost-effective but bears some serious complications including malignancy. Therefore, active screening for cancer is of utmost importance. The aim of this study was to assess the prevalence of malignancy in dialyzed patients in relation to status on the on the waiting list and type of dialysis. This cross-sectional study was conducted in 108 hemodialyzed patients (mean age 65 years, 47 women) and 47 peritoneally dialyzed patients (mean age 51 years, 25 women). Among the population studied, 20 patients were actively waitlisted, including 14 peritoneal dialysis patients. Patients who had been active on the cadaver kidney waiting list and not listed did not differ in regard to sex, dialysis vintage, and causes of end-stage renal failure, but were significantly younger. Among hemodialysis patients, 24 of them had a history of malignancy and 10 in the peritoneal dialysis population. The most common were renal cell carcinoma in 6, breast cancer in 4, lung cancer in 3, prostate cancer in 3, hepatocellular cancer in 2, colorectal cancer in 2, esophageal cancer in 2, and others 14. In waitlisted patients, only 2 hemodialysis patients had a history of malignancy. Waitlisted patients represent a very selected and healthier dialyzed population. Malignancy has become a more common comorbidity in dialyzed patients, which may have important clinical implication regarding therapy. Guidelines for cancer screening in potential transplant recipients should be developed, as nowadays there are scarcity of data in this matter.     

Alkali delivery in chronic hemodialysis: Would more acetate be helpful?

The dialysate alkali used in hemodialysis to replace low body alkali levels in end stage renal disease (ESRD) patients has changed over time from bicarbonate to acetate and finally back to bicarbonate with a small addition of acetate. The ideal way to replace alkali in dialysis patients remains uncertain. Elsewhere in this issue of the journal, Sargent and Gennari, who have contributed greatly to our understanding of dialysis and acid‐base kinetics, suggest that decreasing the currently used concentration of bicarbonate while increasing concentration of acetate in the dialysate may be a much more physiological approach to alkali delivery during hemodialysis. These recommendations are based on results from a series of hemodialysis simulations using mathematical theoretical methods, with the assumption that acetate metabolism will be sufficiently delayed with the higher acetate dialysate and reduce the rate of correction of metabolic acidosis during dialysis. Although valuable in calling attention to the issues surrounding alkali repletion during hemodialysis, these postulations should be tested in clinical trials. We believe, however, that the available evidence suggests that the rate of gain of bicarbonate during dialysis with the higher acetate dialysate would not be slower and that the replacement of some dialysate bicarbonate with acetate will not alter alkali accretion or intradialytic pH.     

Acetate intolerance during hemodialysis.

Acetate is frequently substituted for bicarbonate in hemodialysis solutions. Plasma acetate and bicarbonate concentrations were measured in nine patients with chronic renal failure undergoing hemodialysis with dialyzate containing acetate. In three patients (2 children and 1 adult) plasma acetate concentrations exceeded 15 mEq/liter during the dialysis. The mechanisms leading to acetate intolerance are probably multiple. It cannot be assumed that dialysis with acetate containing solutions will restore the buffer anion deficit characteristic of chronic renal failure.     

Acquired cystic disease of the kidneys in chronic hemodialyzed and renal transplant patients

In this study, the appearance of renal cysts in 43 chronic hemodialyzed patients (mean duration of dialysis treatment: 26.3 months) was investigated by sonography with a high resolution (3.5 MHz) sector scanner. In an investigation of the patients' own kidneys, 23 renal transplant patients (mean observation time: 51.3 months after transplantation; mean dialysis treatment before transplantation: 22.8 months) were also studied by sonography. Cysts could be demonstrated in 21 of 43 (49%) patients on maintenance hemodialysis. In 10 of these patients a previous investigation at the beginning of dialysis did not demonstrate any cysts. The diameter of the cysts varied between 5 and 30 mm. With regard to the duration of dialysis, cysts could be demonstrated by sonography in 9 of 23 (39%) dialyzed patients, with a maximum dialysis duration of 2 years, and in 12 of 20 (60%) patients who had been dialyzed for more than 2 years. The development of acquired cystic disease of the kidneys in dialysis patients seems to be promoted by the longer survival of uremic patients. Cysts could be found in the patients' own kidneys in only 4 of 23 (17%) renal transplant patients. The difference in the demonstration of cysts between patients on maintenance hemodialysis and renal transplant patients was statistically significant. This suggests that cystic transformation may possibly be a reversible process.     

Acetate Metabolism During Hemodialysis

We infused acetate into normal human subjects and performed kinetic analysis of the plasma and urine values obtained before, during, and after the infusion. The data were best fitted by a first-order elimination process with a mean metabolic clearance rate of 2.3 L/min. Gotch and Sargent had previously suggested that during dialysis, acetate metabolism was zero order. We performed kinetic modeling of acetate concentrations during dialysis. The data were best fitted to a Michaelis-Menton model (i.e., first-order metabolism at low concentrations and saturated at high concentrations). The mean Km for acetate in the dialysis patients was 8.5 mM and the mean Vmax was 18 mmol/min. Patients with a Vmax less than 7 mmol/min usually had a fall in plasma bicarbonate during dialysis while patients with a Vmax greater than 14 mmol/min usually had a rise in bicarbonate during dialysis. It is concluded that during high-surface-area dialysis, the capacity for acetate metabolism will affect acid-base homeostasis. Kinetic modeling will be useful to define acetate-intolerant patients and may be used to predict patients who will benefit from bicarbonate hemodialysis.     

Serum growth factors in hemodialyzed patients

The contact of chronic hemodialysis patients' blood with components of extracorporeal circulation leads to mobilization of several systemic reactions. The purpose of this study was to determine the activity of transforming growth factor (TGF-beta1) and platelet derived growth factor (PDGF) in serum of patients on long-term hemodialysis program and to compare these results with ones obtained in healthy volunteers. Twenty-five patients on dialysis carried out on polysulfone membrane dialyzer, and 16 patients on dialysis with the used of cuprophan membrane dialyzer on long-term hemodialysis program participated in the study. TGF-beta1 level in serum of healthy volunteers (12.06 +/- 7.56 ng/mL) was lower than in serum of patients dialyzed on polysulfone membrane dialyzers (26.56 +/- 14.83 ng/mL). Differences in PDGF concentrations in serum of control group and hemodialyzed patients were not statistically significant. The strong correlation between TGF-beta1 and PDGF in serum of both studied groups of patients was demonstrated.     

CD31 expression on leukocytes is downregulated in vivo during hemodialysis

BACKGROUND/AIM: CD31 on leukocytes is the adhesion molecule involved in the leukocyte extravasation in inflammatory conditions. During hemodialysis with cellulosic membranes, it is considered that activated leukocytes adhere to endothelium, but do not show extravasation. However, it is not elucidated why activated leukocytes do not show endothelial transmigration during hemodialysis with cellulosic membranes. METHODS: In the present study, changes in the expressions of Mac-1 and CD31 on granulocytes and monocytes were analyzed by flow cytometry during hemodialysis in 7 patients treated with regenerated-cellulose (RC) membranes and next with polysulfone (PS) membranes. RESULTS: During dialysis with RC, Mac-1 expressions on granulocytes and monocytes both significantly increased as compared with predialysis values and across the dialyzer. During dialysis with RC, the CD31 expression on granulocytes and monocytes significantly decreased as compared with predialysis values. During dialysis with PS, changes in Mac-1 and CD31 expressions on granulocytes and monocytes were smaller than those during dialysis with RC. CONCLUSIONS: Decreased CD31 expression on leukocytes may affect leukocyte function more in patients chronically hemodialyzed with RC than in those hemodialyzed with PS, since CD31 is important in leukocyte transendothelial migration in inflammatory conditions.     

Respiratory gas exchange by high-efficiency hemodialyzers

The effects of respiratory gas mass-transfer by high-efficiency hemodialyzers with regard to respiratory status and acid-base balance were studied in three groups of patients. Patients dialyzed with acetate dialysate and a single pass delivery system (group I) and those dialyzed with the same dialysate and a recirculating single pass system (group II) had significant intradialytic decreases in PCO2 (p is less than 0.05), while patients hemodialyzed aginst a carbon dioxide/bicarbonate dialysate (group III) had no significant alterations in arterial PCO2. The massfransfer rate of carbon dioxide was 0.3 mM/min in group I and 0.2 mM/min in group II. The hypocapnia caused by dialyzer mass-transfer of carbon dioxide was associated with a significant drop in minute ventilation volume and a decrease in PO2 which was significant in group I (p is less than 0.05). Although bicarbonate mass-transfer reduced serum bicarbonate levels, the loss of carbon dioxide to the dialysate resulted in an increased arterial pH during dialysis.