Bicarbonate-based Dialysis Solutions Research Articles

Outcome of patients on haemodialysis in Khuzestan, Iran.

Sir The prevalence and incidence rate of patients treated for end-stage renal disease (ESRD) undergoing haemodialysis is increasing in Iran, from 98 and 38.2 pmp to 169 and 66 pmp in 2004, respectively [1, 2]. Although many studies on the survival of patients with ESRD have been done in developed countries, lack of data from developing countries still exists. This epidemiologic retrospective study was conducted in patients with ESRD referred to nine haemodialysis centres in Khuzestan province of Iran. The period of study was 15 years, started in 1994 and finished in 2009. Haemodialysis was performed for 9–12 h, three times a week, using semi-synthetic (cellulose diacetate) or synthetic (polysulphone) dialysis membranes. Acetate-based dialysis solution was used till January 2006 and bicarbonate-based dialysis solution, thereafter, at a delivered bicarbonate concentration of 35 mEq/L. We included only patients with ESRD on maintenance haemodialysis treatment, who were dialysed >90 days before entering the study. Patients who died within the first 90 days of commencing dialysis were excluded. Other exclusion criteria were incomplete data of patients, haemodialysis because of acute renal failure, kidney transplantation or peritoneal dialysis as renal replacement therapy at any time of study. The study was carried out under the approval of Ahvaz Jundishapur University of Medical Sciences Ethical Committee. Over a 15-year period follow-up, overall 1312 patients with ESRD underwent haemodialysis in nine haemodialysis centres. After exclusion, data were analysed of 846 patients, 467 (55.2%) were male and 379 were female (44.8%). At the start of haemodialysis, the mean age of all patients was 51.8 ± 17.0 years (range, 6–90 years). The survival analysis was performed in 846 patients. The mean and median follow-up duration were 32.7 and 23.0 months, respectively. The mean patient survival at the end of 1 year was 10.6 months [95% confidence interval (CI): 10.4–10.8], 23.4 months (95% CI: 22.4–24.4) at 3 years, 28.2 months (95% CI: 26.4–30.0) at 5 years, 27.8 months (95% CI: 25.4–29.8) at 7 years and 26.8 months (95% CI: 24.4–29.2) at 10 years of follow-up. Table 1 and Figure 1 show the survival of patients according to diabetic status. Fig. 1. Ten-year survival of diabetic and non-diabetic patients on haemodialysis patients (0.6 versus 4.5%; P < 0.001). Table 1. One-, 3-, 5-, 7-, and 10-year survival of patients according to diabetic status Although maintenance dialysis in patients with ESRD prevents death from uraemia, patient survival remains an important issue. We could not find published data that evaluated 10-year survival of patients on haemodialysis in Iran. This study shows that the survival of our patients is catastrophic and was much lower than that reported from many centres in the UK, Europe, Japan and France [3, 4]. Lower survival of diabetic patients on haemodialysis compared with non-diabetics has been demonstrated in other studies as well. Some factors play a role in the poor prognosis of diabetic patients with ESRD, including cardiovascular diseases, problems with vascular access and arteriovenous fistula, foot ulcers, infection, body weight during haemodialysis intervals and higher drops in blood pressure during haemodialysis. According to the very poor prognosis of diabetic dialysis patients, it appears that using other replacement therapy including kidney transplantation could be more important.

Hemodiafiltration with Endogenous Reinfusion with and without Acetate-Free Dialysis Solutions: Effect on ESA Requirement

Background: Hemofiltrate reinfusion (HFR) is a form of hemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient ‘regenerated’ through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine hemodialysis and HDF contain small quantities of acetate (3–5 mM) as a stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. The impact of AF DS during HFR on Hb levels and erythropoietic-stimulating agent (ESA) requirement in chronic dialysis patients was assessed. Patients and Methods: After obtaining informed consent, 30 uremic patients treated by standard bicarbonate dialysis (BHD, DS with acetate) were randomized to treatment in 3-month cycles: first AF HFR, followed by HFR with acetate, and again AF HFR. At the beginning and end of each period, Hb and ESA requirements were evaluated. Results: A significant increase in the Hb level was observed throughout all periods of HFR versus BHD (from 11.1 to 11.86 g/dl; p = 0.04), with a significant decrease of ESA requirements from 29,500 to 25,033 IU/month (p = 0.04). Conclusion: Regardless of the presence or absence of acetate in DS, HFR per se allows a significant lowering of ESA dosage versus BHD, while at the same time increasing Hb levels. Taking for granted the clinical impact produced, HFR seems to provide a relevant decrease in end-stage renal disease patient costs.

Effects of acetate-free haemodiafiltration (HDF) with endogenous reinfusion (HFR) on cardiac troponin levels

Haemofiltrate reinfusion (HFR) is a form of haemodiafiltration (HDF) in which replacement fluid is constituted by ultrafiltrate from the patient 'regenerated' through a cartridge containing hydrophobic styrene resin. Bicarbonate-based dialysis solutions (DS) used in routine haemodialysis and HDF contain small quantities of acetate (3-5 mMol/L) as stabilizing agent, one of the major causes of intradialytic hypotension. Acetate-free (AF) DS have recently been made available, substituting acetate with hydrochloric acid. Cardiac troponin (cTnT) constitutes an appreciable marker of myocardial damage and cardiac hypertrophy, and correlates with left ventricular mass. The aim of this study was to assess the impact of the presence or lack of acetate in DS on cTnT levels in patients treated with HFR and to evaluate outcome of intra-session cardiovascular stability. Twenty-five patients devoid of major cardiovascular comorbidity were randomized and treated with AF HFR for 3 months. The same patients were subsequently treated by means of HFR with DS containing 3 mMol/L acetate for 3 months and finally with AF HFR for a further 3 months. Prior and subsequent to each treatment period, samples were collected for cTnT measurement. A significant decrease was observed in cTnT levels throughout the first session of AF HFR (1.32 ± 0.35-1.12 ± 0.31 ng/mL, P < 0.05) with a subsequent rise being registered during HFR with acetate-containing DS (1.12 ± 0.31-1.28 ± 0.37 ng/mL, P < 0.05) and a further drop from 1.28 ± 0.37 to 1.21 ± 0.35 ng/mL in the last AF HFR period. During HFR with acetate-containing DS, a significant drop in systolic and diastolic arterial pressure was observed in conjunction with a higher heart rate at the end of the session. We observed an increase in cTnT during HFR with acetate and drops manifested during HFR without acetate; it may therefore be concluded that the drop in cTnT level, significantly correlated with lack of acetate, is indicative of improvement of cardiac microvascular function.

Effect of Bicarbonate-Based Dialysis Solutions on Intracellular Ph (Phi) and Tnfα Production by Peritoneal Macrophages

To compare the effect of Dianeal and two newly-formulated bicarbonate-based peritoneal solutions on intracellular pH (pHi), tumor necrosis factor-alpha (TNFalpha) mRNA level, and TNFalpha secretion by peritoneal macrophages (PMphi). Peritoneal macrophages were isolated from dialysates collected after overnight dwells in peritonitis-free continuous ambulatory peritoneal dialysis patients. Dialysis solutions contained 1.5% or 4.25% dextrose. HCO3 concentrations of bicarbonate-(TB) and bicarbonate/lactate-buffered (TBL) solution were 38 mM and 25 mM, respectively. TBL also contained lactate at a concentration of 15 mM. pCO2 levels were 78 mmHg and 51 mmHg, respectively. In all experiments pCO2 was carefully maintained at a stable level. The pHi was measured by spectrofluorometry in BCECF-loaded PMphi exposed to different dialysis solutions or Hank's balanced salt solution. TNFalpha levels were measured by ELISA in the supernatant of lipopolysaccharide- (LPS) stimulated PMphi after their incubation in different solutions for 15 and 30 minutes. TNFalpha mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR) of total RNA extracted from LPS-stimulated PMphi after their incubation in different solutions for 30 minutes. beta-actin mRNA was used as the control. Dianeal caused a profound drop in pHi to below 6.2. Following an initial drop, pHi stabilized after 4 minutes at levels of 6.96 and 6.8 after incubation in TB and TBL, respectively. In comparison to the control solution, a fall of 11% and 21% in TNFalpha secretion was seen after incubation in TB for 15 and 30 minutes, respectively, and 15% and 26% after incubation in TBL. Under identical conditions, Dianeal (Baxter, McGaw Park, IL, U.S.A.) caused 59% and >95% suppression of TNFalpha secretion. Accordingly, TNFalpha mRNA level in PMphi was severely depressed by Dianeal but no detectable inhibition was observed following incubation for 30 minutes in TB and TBL. When dextrose concentration in TB and TBL was increased from 1.5% to 4.25%, TNFalpha secretion by PMphi was not suppressed by more than 49%, even after 30 minutes incubation. Moreover, suppression of TNFalpha mRNA levels could not be detected with TB or TBL even at high dextrose concentrations. In contrast to Dianeal, both bicarbonate-based solutions caused only a mild drop in pHi of PMphi. We postulate this effect to be responsible for the improved capacity of PMphi to secrete TNFalpha when incubated in bicarbonate-based solutions compared to Dianeal. Reflecting its known cytotoxicity, dextrose in high concentrations diminishes the protective effect of TB and TBL on immune function of PMphi. TBL is as effective as TB in preventing the deleterious effect of Dianeal on PMphi function.

Improved cytosolic free calcium mobilization and superoxide production in bicarbonate-based peritoneal dialysis solution.

Intraperitoneal phagocytes play an important role in local host defence to prevent CAPD peritonitis. The intracellular calcium [Ca2+]i is thought to be involved in the regulation of various cell functions. This study therefore investigates the effect of lactate-based dialysis solution (LBDS) and bicarbonate-based dialysis solution (BBDS) on cytosolic free calcium mobilization and superoxide production (SP) as important steps in signal transduction and bacterial killing. We studied changes in [Ca2+]i and SP following stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP) in polymorphonuclear neutrophils (PMNs) incubated in either LBDS-pH 5.2, LBDS adjusted to pH 7.4, 1:10 diluted spent and fresh LBDS or BBDS-pH 7.4 with different glucose concentrations, comparing the data with cells treated with Hanks buffer (HBSS) pH 7.4 as control. To elucidate the effect of glucose and lactate PMNs were additionally incubated in HBSS-pH 7.4, containing glucose (HBSS-Glu-pH 7.4) or lactate (HBSS-Lact-pH 7.4) in the same concentrations as contained in CAPD solutions and tested as above. PMNs were isolated from healthy blood donors and incubated with dialysis solution 10 min prior to stimulation with fMLP. [Ca2+]i mobilization and SP were completely inhibited in PMNs incubated in LBDS pH 5.2. pH adjustment of LBDS to 7.4 and 1:10 dilution of spent and fresh LBDS corrected some of the suppression of the calcium influx and superoxide production. BBDS pH 7.4, however, preserved physiological cell function significantly better at low (1.5 and 2.3%) glucose concentrations. In comparison to conventional lactate-based dialysis solution, pH adjusted and 1:10 diluted LBDS, bicarbonate-based dialysis solution is more biocompatible since it preserves significantly better neutrophil cell functions.

Bicarbona Te-Based Dialysis Solution Preserves Granulocyte Functions

Intraperitoneal phagocytes play an important role in local defense in preventing continuous ambulatory peritoneal dialysis (CAPD) peritonitis. This study therefore investigates the effect of the conventional lactate-based dialysis solution-pH 5.2 (LBDS-pH 5.2) and a bicarbonate-based dialysis solution (BBDS) on various cell functions. We studied C5a-induced actin polymerization (AP) as a measure of the cytoskeletal alteration, phagocytosis of zymosan particles, and chemotaxis in neutrophils incubated in either LBDS-pH 5.2, LBDS-pH 7.4, or BBDS-pH 7.4, comparing the data with cells treated with phosphate-buffered saline-pH 7.4 (PBS-pH 7.4) as a control. Polymorphonuclear neutrophils (PMNs) were isolated from the blood of healthy donors and incubated with dialysis solution prior to the experiment. C5a-induced AP was dramatically inhibited in PMNs incubated in LBDS-pH 5.2, paralleled by a complete inhibition of phagocytosis and C5a-induced chemotaxis. In comparison, BBDS improved AP to values above the control and also nearly normalized phagocytosis. Chemotaxis markedly improved in cells treated with the low glucose-containing BBDS (Bic 20), containing high glucose concentrations (Bic 30). In comparison with conventional lactate-based dialysis solution-pH 5.2, bicarbonate-based dialysis solution at low osmolality better preserves neutrophil functions that involve the cytoskeleton.