Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis

Acid-base balance and peritoneal membrane longevity are of utmost relevance for pediatric patients undergoing peritoneal dialysis (PD). PD fluids with neutral pH and reduced glucose degradation product contents are considered more biocompatible, because they preserve peritoneal cell functions in vitro. To investigate the clinical effects of a novel PD fluid buffered with 34 mM pure bicarbonate at neutral pH, a randomized, prospective, crossover comparison with conventional, acidic, 35 mM lactate PD fluid was performed for two consecutive 12-wk periods with 28 children (age, 6 mo to 15 yr) undergoing automated PD (APD). Blood bicarbonate levels and arterial pH were significantly higher after 3 mo of bicarbonate PD (24.6 +/- 2.3 mM and 7.43 +/- 0.06, respectively), compared with lactate PD (22.8 +/- 3.9 mM and 7.38 +/- 0.05, respectively; P < 0.05). This effect was reversible among patients who returned from bicarbonate to lactate fluid. Low initial pH and young patient age independently predicted increased blood pH during bicarbonate APD. Peritoneal equilibration tests revealed subtle changes in solute transport, with a less steep creatinine equilibration curve during bicarbonate dialysis, suggesting reduced peritoneal vasodilation. The peritoneal release of carcinogen antigen-125 increased twofold during bicarbonate APD (29 +/- 15 versus 15 +/- 8 U/ml per 4 h, P < 0.01), which is consistent with recovery of the mesothelial cell layer. This effect was fully reversed when the patients returned to lactate fluid. Effluent carcinogen antigen-125 levels were inversely correlated with peritoneal glucose exposure during lactate but not bicarbonate APD, indicating improved in vivo mesothelial cell tolerance of high-dose glucose with the neutral-pH PD fluid with reduced glucose degradation product content. Among children undergoing APD, neutral-pH, bicarbonate-buffered PD fluid provides more effective correction of metabolic acidosis and better preservation of peritoneal cell mass than do conventional, acidic, lactate-based fluids.     

Biocompatibility pattern of a bicarbonate/lactate-buffered peritoneal dialysis fluid in APD: a prospective, randomized study.

BACKGROUND: In chronic ambulatory peritoneal dialysis, bicarbonate-buffered fluids, with their neutral pH and less advanced glycosylation end-products (AGE) and glucose degradation products (GDP), have better biocompatibility than conventional peritoneal dialysis (PD) solutions. That difference may be more beneficial in automated peritoneal dialysis (APD), due to its more frequent exchanges and longer contact times with fresh dialysate. We performed a prospective, randomized study in APD patients to compare the biocompatibility of conventional and bicarbonate/lactate-buffered PD fluids. METHODS: We randomized 14 APD patients to have APD with either conventional or bicarbonate/lactate-based fluids. After 6 months, both groups changed to the other solution. The overall observation period was 12 months. After 1 and 5 months and again after 7 and 11 months, phagocytotic and respiratory burst capacities of effluent peritoneal macrophages were determined. Plasma interleukin (IL)-6 and C-reactive protein (CRP) as well as effluent IL-6, CRP, transforming growth factor (TGF)-beta 1, AGE and CA125 concentrations were measured. Inflow pain was quantified using a patient questionnaire. RESULTS: Respiratory burst capacity remained unchanged and phagocytotic activity increased significantly during APD (P<0.001) with the bicarbonate/lactate fluid. Effluent IL-6 release was significantly lower than with the lactate fluid (P<0.05). While in the effluent TGF-beta 1 was unaffected, AGE concentration was lower after bicarbonate/lactate treatment (P<0.05). Effluent CA125 concentration, an indicator of mesothelial cell integrity, was higher (P<0.05) in neutral effluents. Finally, patients' inflow pain diminished (P = 0.05) when using the neutral fluid. CONCLUSIONS: The use of a neutral PD fluid in APD improved patients' inflow pain as well as biocompatibility parameters reflecting enhanced phagocytotic activity of peritoneal macrophages, reduced constitutive inflammatory stimulation (IL-6), reduced AGE accumulation in the peritoneal cavity and better preservation of the mesothelial cell integrity. From the biocompatibility point of view, a neutral fluid with low GDP content can be recommended as the primary choice for APD.     

Continuous veno-venous haemodialysis with a novel bicarbonate dialysis solution: prospective cross-over comparison with a lactate buffered solution.

OBJECTIVE: To compare acid-base balance, lactate concentration and haemodynamic parameters during continuous veno-venous haemodialysis (CVVHD) using bicarbonate or a lactate buffered dialysate. METHODS: Design: prospective randomized cross-over design; Setting: Multicentre combined adult surgical and medical intensive care units. Patients; 26 critically ill patients starting CVVHD for acute renal failure. Interventions: Each patient to receive 48 h of bicarbonate dialysate and 48 h of lactate dialysate with the order of the 48 h block randomized at trial entry. RESULTS: The serum bicarbonate increased from baseline in both the lactate and bicarbonate groups over the first 48 h of treatment (16.3+/-1.53 to 22.2+/-1.41 mmol/l and 18.9+/-2.02 to 22.2+/-1.18 mmol/l, respectively) and continued to rise towards normal over the next 48 h after cross-over to the other dialysate. The H+ and pCO2 only trended higher in the lactate group. Unlike the acid base parameters, serum lactate levels varied depending on the dialysate composition. The patients initially randomized to the lactate dialysate had higher serum lactate levels and these tended to increase further after 48 h of dialysis from 2.4+/-0.8 to 2.6+/-0.4 mmol/l. However, in the following 48 h the lactate levels fell to 1.8+/-0.6 (P = 0.039) while patients were being treated with the bicarbonate dialysate. Similar results were seen in the patients initially randomized to the bicarbonate dialysate. Serum lactate remained stable over the first 48h (1.4+/-0.2 to 1.5+/-0.1 mmol/l) but after cross-over to the lactate dialysate increased to 3.1+/-0.7 mmol/l (P = 0.051). Overall, lactate levels were significantly higher during dialysis with lactate buffered solution than bicarbonate buffered solution (2.92+/-0.45 vs. 1.61+/-0.25 mmol/l P = 0.01). Mean arterial pressure trended higher during bicarbonate dialysis but did not reach statistical significance (lactate vs. bicarbonate; 71.1+/-3.1 vs. 81.3+/-5.8 mm Hg). Subgroup analysis of the patients with abnormal liver indices or increased lactate levels at initiation of dialysis (n = 15) revealed only a trend toward better bicarbonate control (lactate vs. bicarbonate; 22.00+/-1.73 vs. 22.86+/-1.09, P = 0.2). However, in this group with hepatic insufficiency elevations in serum lactate were even greater during lactate compared to the bicarbonate dialysis (3.39+/-0.68 vs. 1.78+/-0.42 P = 0.036). Patients who had elevations of lactate during lactate dialysis had a high mortality (6 of 7). These patients had an even greater disparity in lactate levels (4.3+/-1.4 vs. 1.3 +/-0.3) and blood pressure (68.0+/- 7.7 vs. 87.2+/-17.1) between lactate and bicarbonate dialysis. Due to small patient numbers these comparisons did not achieve statistical significance. CONCLUSION: During continuous veno venous haemodialysis a bicarbonate buffered dialysis solution provided equal acid-base control but maintained more normal lactate levels than a lactate buffered dialysis solution.     

Effects of pH-neutral, bicarbonate-buffered dialysis fluid on peritoneal transport kinetics in children

BACKGROUND: Due to their superior biocompatibility, pH-neutral solutions are beginning to replace acidic lactate-buffered peritoneal dialysis (PD) fluids. We hypothesized that pH-neutral and acidic solutions might differentially affect peritoneal transport in the early dwell phase, due to differences in ionic shifts and initial peritoneal vasodilation. Such differences may become clinically relevant in patients with frequent short cycles on automated PD (APD). METHODS: Twenty-five children were treated with a lactate-buffered (35 mmol/L, pH 5.5) or a bicarbonate-buffered PD solution (34 mmol/L, pH 7.4) in randomized order on two sequential days. Each day a four-hour Standardized Permeability Analysis (SPA) was performed, followed by overnight APD (7 cycles, fill volume 1000 mL/m2, dwell time 75 min). Functional peritoneal surface area was dynamically assessed using the three-pore model. RESULTS: While intraperitoneal pH was constant at 7.41 +/- 0.03 throughout the SPA with bicarbonate fluid, the dialysate remained acidic for more than one hour with lactate solution (pH 7.12 +/- 0.08 at 1 h). Total pore area was 60% higher during the first 30 minutes of the dwell than under steady-state conditions, without a difference between acidic and pH-neutral fluid. Net base gain, intraperitoneal volume kinetics, glucose absorption, ultrafiltration rate, effective lymphatic absorption and the transport of urea, potassium, beta2-microglobulin and albumin were similar with both fluids. However, phosphate and creatinine elimination were 10% lower with bicarbonate PD fluid, resulting in corresponding significant decreases in the 24-hour clearances of these solutes. CONCLUSION: The peritoneal surface area is not measurably influenced by pH-neutral PD fluid. Creatinine and phosphate elimination appears to be slightly reduced with bicarbonate fluid; this observation awaits clarification in extended therapeutical trials.     

Improved effect of hemodialysis on acidemic patients from an acetate concentration of 38 mmol/l

A high frequency of metabolic acidosis in a group of 30 patients on regular dialysis treatment initiated a study of the effect (and possible side effects) of a higher concentration of acetate in the dialysate. The concentration of acetate in the dialysate was increased from 32.6 ('low ac') to 38.2 mmol/l ('high ac'). The 'low ac' dialysis treatment changes the metabolic acidoses (mean pH = 7.34; base excess, BEb = - 8.3 mmol/l) to chronic hypocapnia (pH = 7.40; BEb = - 5.4 mmol/l). 'High ac' normalized the acid base status (pH = 7.44; BEb = -0.6 mmol/l). No side effects occurred. Since PaCO2 does not change much during hemodialysis it is convenient to look at the linearly related changes of the pH and the logarithmic standard bicarbonate concentration along iso-PCO2 lines in a log standard bicarbonate-pH-nomogram.     

Dialysate bath and QTc interval in patients on chronic maintenance hemodialysis: pilot study of single dialysis effects

Introduction: Serum concentrations of potassium (K) and calcium (Ca) influence ionic currents and play an important role in the duration of ventricular action potential. Further, the influence of alkalosis in reducing ionized calcium has been well known for a long time. The aim of this study was to assess the effects of different dialysate electrolytes and bicarbonate concentrations on changes of QTc interval in patients on chronic hemodialysis. Methods: The study hemodialysis sessions were performed in 22 patients, with different electrolyte and bicarbonate concentrations in dialysate. Tested dialysate concentrations were K of 2 and 3 mmol/L; Ca 1.25, 1.5 and 1.75 mmol/L; and bicarbonate 30 and 34 mmol/L. An electrocardiogram (ECG) was recorded 1 hour before, at the end and every hour for 4 hours after each study dialysis session. QTc interval was measured from the beginning of the QRS complex to the end of a T wave on a 12-lead ECG. Blood was collected and K, total Ca, ionic Ca and pH evaluated. Results: At the end of the study hemodialysis session with dialysate containing low K (2 mmol/L), low Ca (1.25 mmol/L) and high bicarbonate concentration (34 mmol), mean QTc interval was significantly prolonged compared with that recorded with dialysate containing high K (3 mmol/L), high Ca (1.75 mmol/L) and bicarbonate (30 mmol) (40 ± 10 milliseconds vs. 2 ± 2 milliseconds; p<0.01). Dialysate with low concentration of low Ca, K and high concentration of bicarbonate was an independent predictor of QTc; the combination of low Ca and K and high bicarbonate strongly increased the risk of prolonged QTc interval. Conclusion: The present pilot study shows that changes in QTc interval during hemodialysis depend on both electrolyte and bicarbonate concentrations in dialysate.     

A controlled trial of two bicarbonate-containing dialysis fluids for CAPD - Final report

Background. The combination of a low pH and a high concentration of lactate which is present in most dialysis fluids is found to be cytotoxic in vitro. For these reasons it would seem logical to use a bicarbonate-containing solution and thus automatically provide a solution with a neutral pH. Methods. A parallel, randomized, open-label, prospective 2-month trial with an optional 4 month extension was undertaken to compare two novel bicarbonate-based solutions; one containing 38 mmol/l of bicarbonate (B), and one containing a mixture of 25 mmol/l bicarbonate and 15 mmol/l of lactate (B/L), with a control solution containing 40 mmol/l lactate. Results. Three groups of 19 (C), 20 (B), and 20 (B/L) patients were recruited and data from approximately 55 patient months were accumulated in each group. The data show that both bicarbonate-based solutions maintain acid-based levels within the normal range, that there were no changes in any of the other blood biochemistry parameters measured in the peritoneal equilibration test or with regard to adequacy of dialysis, and that furthermore, both solutions were well tolerated. Conclusions. This study showed that either the bicarbonate or bicarbonate/lactate solutions could be utilized efficaciously in patients undergoing CAPD. Keywords: acidosis; alkalosis; bicarbonate; biocompatibility; lactate; peritoneal dialysis      

Dialysis efficacy during acetate-free biofiltration

Background. Acetate-free biofiltration (AFB) is a haemodiafiltration technique based on continuous post-dilution infusion of a sterile isotonic bicarbonate solution. We performed a long-term randomized prospective trial to compare dialysis efficacy and metabolic control of AFB versus bicarbonate haemodialysis (HD). Methods. The AFB group consisted of 11 and the HD group of nine patients, matched for age, sex and urea reduction rate. Biochemical parameters were obtained every 3 months for 1 year (haemoglobin, calcium, phosphate, urea, pre- and post-dialysis bicarbonate, and parathormone (PTH)) and medication was updated. Efficacy of dialysis calculated by KT/V using the dialysate sampling method was determined every 3 months. In AFB patients, the infusion rate of bicarbonate solution was adjusted individually to obtain bicarbonate values of ⩾22 mmol/l before dialysis and ⩽32 mmol/l after dialysis. In the HD group, bicarbonate was added as oral medication to match these bicarbonate concentrations. Statistical analysis was performed using ANOVA for repeated measurements. Results. Pre-dialysis serum bicarbonate levels had risen to the same extent in both groups at the end of the study period (AFB from 21.8 to 26.1 mmol/l, P<0.001, and HD from 20.8 to 24.9 mmol/l, P<0.001). Post-dialysis bicarbonate level was higher in the AFB than in the HD group (P<0.01). Calcium and phosphate levels remained stable in both groups. PTH increased in both groups (AFB from 10.6 to 23.7 pmol/l, and HD from 24.6 to 32.8 pmol/l), with a significant rise only in the AFB patients (P<0.013). Finally, haemoglobin levels and erythropoietin dosage did not change in either group. No significant differences between the two groups were observed. Conclusions. Acidosis was better corrected in AFB without the need for oral supplementation of bicarbonate. However, neither serum calcium nor phosphate levels changed. The observed increase in PTH in the AFB group remains to be clarified. Dialysis efficacy, measured as KT/V, improved during AFB.     

High bicarbonate dialysate in haemodialysis patients: effects on acidosis and nutritional status

Background: Metabolic acidosis adversely affects both protein and bone metabolism in patients with chronic renal failure, and could also affect morbidity and mortality. This trial aimed to investigate the effects of different dialysate bicarbonate concentrations on control of acid base balance, and nutritional status. Methods: Forty-six stable haemodialysis patients were dialysed using LowBic. (30 mmol/l) or HighBic. (40 mmol/l) bicarbonate dialysate in a single blind double crossover trial, of two consecutive six-month periods. Blood gas analysis, anthropometric indices and dialysis dose were measured, in addition to biochemical indices. Results: Predialysis 'arterial' plasma pH values were significantly higher when using the HighBic. dialysate (LowBic. 7.38±0.05, HighBic. 7.43±0.04, P <0.001), as was predialysis serum total CO2 at all times during the study (P <0.01). Kt/V, (LowBic. 1.27±0.19, HighBic. 1.27±0.05), urea generation rates (UGR) (LowBic. 1.99±0.77, HighBic. 1.92±0.77 mmol/min), and normalized protein catabolic rate (NPCR) (LowBic. 1.04±0.26, HighBic. 0.99±0.28 g/kg/day) did not differ, and values of parathyroid hormone (PTH) were comparable. Triceps skinfold thickness (TSF) showed a significant change (LowBic. 14.8±6.9-11.8±5.5, HighBic. 14.9±6.3-15.8±6.4 mm, P <0.05) which was reverse following dialysate change (HighBic. 11.8±5.5-13.3±7.2, LowBic. 15.8±6.4-13.8±6.7 mm, P <0.05). No differences in mid upper arm circumference were found. Conclusions: Bicarbonate dialysate concentrations of 40 mmol/l were safe, well tolerated, and produced better control of acidosis, with an increase in TSF, compared to a bicarbonate concentration of 30 mmol/l.     

Substitution of Acetic Acid for Hydrochloric Acid in the BicarbonateBuffered Dialysate

Abstract: In a multicenter study including 5 dialysis units, blood acetate changes during 4 h dialysis sessions in 141 patients treated with a 4 mM acetate-containing bicarbonate dialysate (ABD) were evaluated and compared to the values of 114 patients using an acetate-free bicarbonate dialysate (AFD). Acetate-free bicarbonate dialysate was delivered by a dialysis machine from the mixing with water for dialysis of a 1/26.2 bicarbonate concentrate, and a 1/35 acid-concentrate in which acetic acid was substituted for hydrochloric acid (Soludia, Fourquevaux, France). This new type of dialysate was routinely in use for 3 years on average (range, from 2 to 5 years). All patients fasted before and during dialysis. Blood samples were withdrawn at the start and at the end of dialysis sessions. The acetate plasma concentration was determined using the acetyl-CoA synthetase enzymatic method (Boehringer, Manheim, Germany). In patients treated with ABD whose predialysis blood acetate levels were in the physiologic range of ≤100 μM (n = 113), the acetate plasma concentration increased from a predialysis mean value of 22 ± 3 μM to a postdialysis mean value of 222 ± 11 μM in 88 patients (78% of patients) whereas the acetate plasma concentration changes remained in the range of physiologic values from 21 ± 6 to 58 ± 7 μM in the other 25 patients. In contrast, patients treated with AFD whose predialysis blood acetate levels were in the physiologic range (n = 108), acetate plasma concentration increased from a predialysis mean value of 49 ± 6 μM to 160 ± 19 μM in only 13 patients (12% of patients) whereas acetate plasma concentration changes remained in the range of physiologic values of 23 ± 2 to 41 ± 3 μM in most of the patients of this group. In this study, a significant number of patients, whether receiving standard or acetate-free bicarbonate dialysates, exhibited an extremely high acetate plasma concentration at the start of the dialysis session. Hyperacetatemia was controlled with AFD in patients whose predialysis acetate plasma concentration of 316 ± 82 decreased to 55 ± 23 μM (n = 6) at the end of the dialysis session whereas the acetate plasma concentration remained high when the predialysis concentration was 580 ± 76 μM, with a postdialysis concentration of 233 ± 39 μM (n = 28). It is concluded that in patients whose predialysis blood acetate levels were in the physiologic range, acetate-containing bicarbonate dialysate induces hyperacetatemia whereas postdialysis blood acetate remains in the normal range in such dialysis patients treated with acetate-free dialysate. Chronic hyperacetatemia, which could be found in dialysis patients, is well controlled by dialysis using an acetate-free dialysate.     

Bicarbonate and calcium kinetics in postdilutional hemodiafiltration.

Hemodiafiltration (HDF) is a very effective blood treatment resulting from the coupling of dialysis and hemofiltration and leading to reduction of dialysis time. The aim of this study was to evaluate the balance of bicarbonate and calcium through the filter during postdilutional HDF (with an ultrafiltration flow rate of 70 ml/min) and to verify the effect of ultrafiltration on the kinetics of these two solutes. The study was performed by simultaneously collecting three blood samples (at filter inlet and outlet and after reinfusion) at different ultrafiltration flow rates (12.5-90 ml/min), to measure blood pH, pCO2, plasma total CO2(TCO2), total calcium, ionized calcium and plasma protein concentration. Plasma bicarbonate concentration was calculated by measuring plasma TCO2. The results showed an inverse linear relationship between bicarbonate (r: -0.7938; p less than 0.001) and calcium (r: -0.8731; p less than 0.001) balance and ultrafiltration flow rate. In particular, in postdilutional HDF both bicarbonate and calcium balances through the filter were negative at ultrafiltration flow rates greater than 40 and 55 ml/min, respectively. The negative bicarbonate balance, however, was corrected by reinfusing a substituting solution containing bicarbonate (40 mmol/l). By contrast, the negative calcium balance cannot be corrected by reinfusion and requires a greater calcium concentration in the dialysate and oral calcium supplements.     

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.     

Low-potassium and glucose-free dialysis maintains urea but enhances potassium removal.

BACKGROUND: The influence of potassium (K) removal on dialysis efficiency as measured by urea elimination is not clear. In this prospective, randomized, cross-over study we investigated the magnitude of K removal and its effect on urea (u) elimination during high-flux haemodialysis (HD). METHODS: Twelve stable, non-diabetic HD patients were investigated during three one-week standardized HD periods (1.8 m(2) high-flux polysulphone dialyser, treatment time 240 min, Qb = 300 ml/min, Qd = 500 ml/min, dialysate without glucose, bicarbonate 40 mmol/l), using dialysates containing 0 (0K), 1 (1K), and 2 (2K) mmol/l of K. Mass removal of K (M(K)) and u (M(U)) were measured during the mid-week treatment by partial dialysate collection. Urea reduction rate (URR) and Kt/V were determined. RESULTS: 0K, 1K and 2K treatments were perfectly comparable. Plasma K (PK) continuously declined reaching stable concentrations after 180 min. While 0K dialysate removed 117.1 mmol, 80.2 and 63.3 mmol (P < 0.001) were removed by 1K and 2K baths respectively. M(U) was not influenced by M(K) (r = 0.22) and amounted to 491.1 (0K), 508.6 (1K), and 506.2 (2K) mmol (NS) respectively. Accordingly, urea clearance, URR and Kt/V were constant during 0K, 1K and 2K treatments. CONCLUSIONS: Potassium-free dialysate significantly enhances potassium elimination. Potassium removal has no influence on urea elimination. High potassium removal, when needed, does not impair dialysis efficiency as measured by urea kinetics in high-flux, glucose-free, 40 mmol/l bicarbonate HD.     

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.     

A comparison of solute clearance and ultrafiltration volume in peritoneal dialysis with total or fractional (50%) intraperitoneal volume exchange with the same dialysate flow rate

Background: The most efficient way to perform automated peritoneal dialysis (APD) has not yet been defined. Tidal peritoneal dialysis (TPD) has been claimed to be more efficient than traditional intermittent peritoneal dialysis (IPD), but few comparative studies have been done keeping dialysate flow the same in the two treatment techniques. Method: Six patients were treated with 10, 14 and 24 litres total dialysis fluid volume during 9 h (flow rate 18,5, 25.9 and 44.4 ml/min), receiving the treatments both as IPD and TPD. Glucose concentration in the fluid was held constant during all treatments. Transperitoneal clearances (ml/min) for urea, creatinine and uric acid and ultrafiltration volume was calculated, and comparisons made between TPD and IPD. The total intraperitoneal dwell time was calculated for each treatment session. A peritoneal equilibration test was also done for each patient. Results: The ratio of the creatinine concentration in dialysate to the concentration in plasma at 4 h obtained with the peritoneal equilibration test (PET) averaged 0.77 (range 0.69-0.82). Urea clearance was higher for IPD than for TPD with 10 litres: 14.3±2.4 and 13.3±2.7 (P=0.0092). For 14 and 24 litres urea clearance for IPD and TPD was 17.9±2.3 and 15.9±3.5 (n.s.) and 20.9±3.6 and 19.9±5.6 (n.s) respectively. Creatinine clearance was higher for IPD than for TPD with 10 litres: 9.6±1.3 and 8.9±1.3 (P=0.0002). For 14 and 24 litres creatinine clearance for IPD and TPD was 11.0±0.7 and 9.9±2.0 (n.s.) and 12.3±1.2 and 12.4±2.2 (n.s.) respectively. Uric acid clearance was higher for IPD than for TPD with 10 litres: 8.4±1.3 and 7.7±1.0 (p=0.0054). For 14 and 24 litres uric acid clearance for IPD and TPD was 9.4±1.7 and 8.9±2.2 (n.s.) and 11.3±2.9 and 10.6±2.6 (n.s.) respectively. IPD gave significantly higher ultrafiltration volume (ml) than IPD for both 10 and 14 litres: 944±278 and 783±200 (P=0.0313) and 1147±202 and 937±211 (P=0.0478). For 24 litres there was no significant difference between IPD and TPD: 1220±224 and 1253±256. Conclusion: With the lowest dialysate flow rate (18.5 ml/min), solute clearance and ultrafiltration volume was higher on IPD than on TPD. With the intermediate flow rate (25.9 ml/min) the ultrafiltration volume was higher on IPD, but no difference was found for solute clearance. With the highest flow rate (44.4 ml/min) there as no difference neither for ultrafiltration nor for solute clearance.     

Clinical effects of long-term use of neutralized dialysate for continuous ambulatory peritoneal dialysis.

The long-term effects of neutralized dialysate used in continuous ambulatory peritoneal dialysis (CAPD) were evaluated in 8 well-controlled patients. Twelve milliliters of 8.4% sodium bicarbonate was added to Dianeal PD-1 immediately before every administration. The final pH was 6.8 and the concentration of sodium bicarbonate was 6 mmol/l. The final sodium level was 138 mEq/l. This dialysate was used for 5 months. For 2 months before and 3 months after this period, Dianeal PD-2 was used as the dialysate for comparison. Blood bicarbonate levels significantly improved during the use of the neutralized dialysate. Blood sodium, chloride and magnesium levels and the effluent volume significantly increased. Sodium balance improved during the period when neutralized dialysate was used. Total leukocyte counts in the effluent decreased, and leukocyte viability increased. Abdominal distention, abdominal pain during instillation, nausea and headache improved. No side effects, including peritonitis, occurred during the trial of neutralized dialysate. The results suggest that this dialysate was less irritating to the peritoneal membrane than the control dialysate and that the therapeutic effects were satisfactory.     

Calcium balance and intact PTH variations during haemodiafiltration

BACKGROUND.: Recent approaches to prevent and treat secondary hyperparathyroidismin dialysis patients include decreasing dialysate Ca contentfrom 1.75 to 1.5 mM or lower. We have recently observed thatby decreasing dialysate Ca to 1.25 mM a rise in intact parathormoneserum levels occurs despite adequately controlled predialysisCa and phosphate serum levels. In that study complementary treatmentwith high-dose 1(OH) vitamin D3 was required to suppress theparathormone. In the present study we aimed to assess the totalCa balance as well as the modifications in parathormone inducedby the dialysis session in order to understand the reasons forwhich the rise in parathormone was induced. METHODS.: Fourteen HD patients treated with haemodi-afiltration threetimes/week gave their informed consent for the study. They weredistributed in two groups with identical treatment but for thedialysate Ca content which was 1.5 and 1.25 mM respectivelyand for the amount of oral CaCO₃ received. Total and ionizedCa, phosphate, pH, and albumin as well as parathormone weremeasured in serum before and after dialysis and in the spentdialysate during two dialysis sessions. RESULTS.: Serum ionized Ca (normalized to pH 7.4) did not change during1.25 mM dialysate Ca and significantly increased with 1.5mM(P<0.001). The end-dialysis values being 1.25±0.02and 1.38±0.02 mM respectively. Total Ca significantlydecreased with 1.25mM dialysate Ca (P<0.04) and increasedwith 1.5mM (P<0.003), the end-dialysis values being 2.51±0.03and 2.75±0.04mM respectively. In the dialysate the differencein ionized Ca concentrations, fresh minus spent dialysate was–1.78±1.12 mmol/l (NS) and 4.26±1.47 mmol/l(P<0.02) respectively for 1.25 and 1.5 mM dialysate Ca. Thedifference in total Ca concentrations, fresh minus spent dialysatewas –0.1±0.01 mmol/l (P<0.005 and –0.002±0.01 mmol/l (NS) respectively. Phosphate removal was higherin 1.25 mM dialysate-Ca-treated patients (40.4±1.75 mmol/sessionversus 34±1.3 mmol/session respectively, P<0.015).The use of 1.25 mM dialysate Ca did not result in a change inserum parathormone, while the use of 1.5 mM resulted in a decreaseof 43±15% (P<0.02) in patients with marked hyperparathyroidism. CONCLUSIONS.: Our data remind us of the difficulty in assessing Ca balancesand identifies the phosphate content as one of the factors influencingthe amount of ionized Ca in the dialysate. Although the long-termparathormone increase we observed using 1.25 mM dialysate Camay well not be explained only by the acute intradialytic modifications,the negative Ca balance identified here (which was missed withthe analysis of ionized Ca alone), and the lack of parathormoneinhibition may participate in the relapse of hyperparathyroidism.     

Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis

Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis. BACKGROUND: Patients on automated peritoneal dialysis (APD) usually receive larger volumes of dialysis solution and more frequent, shorter exchanges than patients on continuous ambulatory peritoneal dialysis (CAPD), and therefore are likely to derive greater benefit from more physiologic solutions. METHODS: Peritoneal dialysis solutions containing 25 mmol/L bicarbonate and either 10 or 15 mmol/L lactate were compared with standard lactate solutions (35 or 40 mmol/L) in two prospective, open-label studies of patients on APD. Each study included a 2-week baseline period (lactate solution), a 6-week treatment period (bicarbonate/lactate solution), and a 2-week follow-up period (same lactate solution as baseline). Biochemical analyses and assessments of vital signs and safety parameters were conducted at baseline, every 2 weeks during treatment, and at the end of the follow-up period. A product use questionnaire was administered in one study at the end of treatment. RESULTS: A statistically significant rise in plasma bicarbonate (approximately 2 mmol/L) occurred when patients switched from a lactate solution to the bicarbonate/lactate solution with equimolar buffer concentration (P < 0.001 for each solution). Plasma bicarbonate decreased by 1.16 mmol/L after a switch from lactate 40 mmol/L to bicarbonate/lactate 35 mmol/L (P < 0.001). When patients switched to bicarbonate/lactate 35, the majority of individual venous plasma bicarbonate values were in the normal range. A switch from a lower calcium (1.25 mmol/ L) lactate solution to a higher calcium (1.75 mmol/L) lactate/bicarbonate solution resulted in a statistically significant rise in serum calcium (0.06 mmol/L, P < 0.018). The product use questionnaire revealed improvements in symptoms, including reduced pain on infusion. CONCLUSION: Bicarbonate/lactate solutions may be used safely and effectively in patients on APD. The availability of 2 formulations with different buffer and calcium content provides flexibility for the control of acidosis as well as calcium balance.     

Mass transfer of calcium across the peritoneum at three different peritoneal dialysis fluid Ca2+ and glucose concentrations

BACKGROUND: In peritoneal dialysis, the rate of ultrafiltration has been predicted to be a major determinant of peritoneal calcium (Ca2+) removal. Hence, dialysis fluid glucose concentration should be an important factor governing the transperitoneal Ca2+ balance. The aim of this study was to test the effect of various dialysate glucose levels and selected dialysate Ca2+ levels on Ca2+ removal in peritoneal dialysis patients. METHODS: Patients (N = 8) received, during a 7-week period, 2 L of lactate (30 mmol/L)/bicarbonate (10 mmol/L)-buffered peritoneal dialysis solutions containing either 1.5% glucose and 1.0 mmol/L Ca2+ or 2.5% glucose and 1.6 mmol/L Ca2+, or 4% glucose and 2.5 mmol/L Ca2+, respectively, provided in a three-compartment bag (trio system). Patients underwent standardized (4-hour) dwells, one for each of the three dialysates to assess permeability-surface area product (PS) or mass transfer area coefficients (MTAC) for ionized and "freely diffusible" Ca2+, lactate, glucose, bicarbonate, phosphate, creatinine, and urea. RESULTS: There was a clear-cut dependence of peritoneal Ca2+ removal on the rate of ultrafiltration. For large peritoneal to dialysate Ca2+ gradients (2.5 mmol/L Ca2+ in 4% glucose) a close fit of measured to simulated data was predicted by the three-pore model using nonelectrolyte equations. For low transperitoneal Ca2+ concentration gradients, however, directly measured Ca2+ data agreed with the simulated ones only when the peritoneal Ca2+ PS was set lower than predicted from pore theory (6 mL/min). CONCLUSION: There was a marked ultrafiltration dependence of transperitoneal Ca2+ transport. Nonelectrolyte equations could be used to simulate peritoneal ion (Ca2+) transport provided that the transperitoneal ion concentration gradients were large. Based on our data 1.38 mmol/L Ca2+ in the dialysis fluid would have created zero net Ca2+ gain during a 4-hour dwell for 1.5% glucose, whereas 1.7 and 2.2 mmol/L Ca2+ would have been needed to produce zero Ca2+ gain for 2.5% glucose and 3.9% glucose, respectively.