Bicarbonate/lactate-based peritoneal dialysis solution increases cancer antigen 125 and decreases hyaluronic acid levels.

BACKGROUND: In a randomized, controlled trial comparing a pH neutral, bicarbonate/lactate (B/L)-buffered PD solution to conventional acidic, lactate-buffered solution (C), the overnight dialysate levels of markers of inflammation/wound healing [hyaluronic acid (HA)], mesothelial cell mass/membrane integrity [cancer antigen 125 (CA125)], and fibrosis [transforming growth factor-beta1 (TGF-beta1) and procollagen I peptides (PICP)] were assessed over a six-month treatment period. METHODS: One hundred six patients were randomized (2:1) to either the B/L group or C group. Overnight effluents were collected at entry into the study (time = 0 all patients on control solution) and then at three and six months after randomization. Aliquots were filtered, stored frozen, and assayed for HA, CA125, TGF-beta1, and PICP. Differences between groups were assessed by repeated-measures analysis of variance for unbalanced data using the SAS procedure MIXED. RESULTS: In patients treated with B/L, there was a significant (P = 0.03) increase in CA125 after six months compared with time = 0 (19.76 +/- 11.8 vs. 24.4 +/- 13.8 U/mL; mean +/- SD; N = 51). In the same group of patients, HA levels were significantly decreased at both three and six months in the B/L-treated group (time = 0, 336.0 +/- 195.2; time = 3 months, 250.6 +/- 167.6; and time = 6 months, 290.5 +/- 224.6 ng/mL; mean +/- SD; P = 0.006, N = 47 and P = 0.003, N = 48, respectively). No significant changes in CA125 or HA levels were observed in the control group. There were no significant changes observed in the levels of PICP or TGF-beta1 in the B/L or C group over the six-month treatment period. CONCLUSIONS: These results suggest that continuous therapy with the B/L solutions modulates the levels of putative markers of peritoneal membrane integrity and inflammation. In the long term, this may positively impact the peritoneal membrane, increasing its life as a dialyzing organ.

Acidosis correction with a new 25 mmol/l bicarbonate/15 mmol/l lactate peritoneal dialysis solution.

OBJECTIVE: The aim of this study was to evaluate the effects of a combined 25 mmol/L bicarbonate/15 mmol/L lactate-based solution (Bic/Lac), compared to a 35 mmol/L lactate solution (Lac)--the most commonly used solution for patients in southern Europe--on the venous plasma bicarbonate level in patients treated with continuous ambulatory peritoneal dialysis (CAPD). DESIGN: This was a randomized, parallel, controlled, open-label study, with patients studied for a period of 3 months preceded by a 1-month baseline and followed by a 1-month follow-up. Patients used the 35 mmol/L lactate solution during baseline and follow-up periods. SETTING: Four Spanish nephrology centers. PATIENTS: Thirty-one (20 Bic/Lac, 11 Lac) well-dialyzed (creatinine clearance > 55 L/week/1.73 m2 body surface area) CAPD patients. INTERVENTIONS: Blood samples were taken for biochemistry tests at all visits. A physical examination was completed at baseline and month 3, and a medical update was completed after 1, 2, and 3 months, and at the follow-up visit. Adverse-event monitoring and notation of prescription changes were carried out continuously. MAIN OUTCOME MEASURE: Effect on venous plasma bicarbonate level. RESULTS: Venous plasma bicarbonate rose by 3.1 mmol/L (confidence intervals 1.6-4.8),from a baseline level of 23.0 mmol/L during the treatment period in those patients treated with Bic/Lac (p < 0.05 vs Lac). The number of acidotic patients (venous plasma bicarbonate < 24 mmol/L) was statistically significantly reduced at every treatment period visit in the Bic/Lac group (p < 0.05). There were no adverse findings with respect to vital signs, physical examination, or clinical symptoms, apart from one death in the control group. CONCLUSIONS: The new Bic/Lac solution allowed better correction of acid-base status than the lactate solution.

A long-term study of a bicarbonate/lactate-based peritoneal dialysis solution--clinical benefits. The Bicarbonate/Lactate Study Group.

OBJECTIVE: A bicarbonate/lactate peritoneal dialysis solution (Bic/Lac) has been developed based on in vitro and ex vivo data showing better preservation of cell function and correction of pain on infusion. DESIGN: This was a randomized, prospective, controlled, open-label study comparing a new 25 mmol/L bicarbonate/15 mmol/L lactate with a standard 40 mmol/L lactate-buffered peritoneal dialysis solution (Lac) over a 12-month treatment period. SETTING: 17 European nephrology centers. PATIENTS: 106 (70 Bic/Lac and 36 Lac) well-dialyzed continuous ambulatory peritoneal dialysis (CAPD) patients. INTERVENTIONS: Dialysis adequacy and peritoneal equilibration test (PET, week -4, months 3, 6, and 12); 24-hour ultrafiltration (week -4, months 1, 3, and 6); blood biochemistry (week -2, day 0, months 1, 2, 3,6, 9, and 12); and a product acceptability questionnaire (months 1 and 6). RESULTS: 88 patients completed the first 6 months, and 44 the full year. The solutions were shown to be therapeutically equivalent with respect to plasma bicarbonate and peritoneal urea and creatinine clearances. Ultrafiltration in the Bic/Lac group increased significantly from baseline by about 150 mL/day for the whole of the 6-month treatment period (p < 0.05). The biochemistry profile, adverse events, and physical examination (except body weight where there was a statistically significant increase in the Bic/Lac group) results did not differ significantly between the two groups. Reduced pain/discomfort on infusion or an increased sense of well-being was reported by 41% of patients on the Bic/Lac fluid. CONCLUSIONS: The Bic/Lac solution is safe and effective in correcting uremic acidosis, provides relief of inflow pain/discomfort, and improves ultrafiltration and body weight.

Biocompatibility of new peritoneal dialysis solutions: clinical experience.

The successful development of peritoneal dialysis (PD) during the last two decades has been made possible by using well-established glucose-based solutions with lactate as buffer. On the other hand, awareness has been increasing about the potentially negative effects of the high concentrations of glucose and lactate, and the low pH of conventional PD solutions. This awareness has prompted an intensive effort to search for and test alternative solutions. As a result, three new, more biocompatible solutions-containing either less glucose or less lactate--are available. Amino acid-based solution uses amino acids instead of glucose as the osmotic agent; it is indicated for treatment of malnutrition. The higher pH and absence of glucose in this solution may prevent alterations of the peritoneal membrane caused by acidity and high glucose concentrations. Bicarbonate/lactate-buffered solution contains a physiologic concentration of bicarbonate and a reduced concentration of lactate; it also has a physiologic pH and markedly reduced levels of glucose degradation products (GDPs). Icodextrin-based solution contains icodextrin as the osmotic agent; it is indicated for long dwells, delivering sustained ultrafiltration for more than 16 hours. This iso-osmolar glucose-free solution may reduce peritoneal membrane alterations caused by glucose or the hyperosmolality (or both) of conventional solutions. Clinical experience of the new solutions is now extensive, and their efficacy and safety are well documented. It therefore seems appropriate to state that we have entered a new era of PD therapy. Each of the new solutions may be less damaging to the peritoneal membrane than conventional solution. In addition, they permit better management of malnutrition and fluid status, and may thus help to improve PD patient survival. Although the effects of each of these new solutions have been well described, clinical documentation of the combined use of these new biocompatible PD solutions is still insufficient. However, the results of studies are expected, during the coming years, to support the combined use of the new solutions as the preferred standard practice for PD.

New solutions for peritoneal dialysis in adult and pediatric patients.

The standard PD solutions used today contain physiological electrolyte profiles similar to that of interstitial fluids and are supplemented with glucose as the osmotic agent. Improvements in solution composition during the last 20 years have been largely restricted to minor changes in buffer and electrolyte levels. Newer PD solutions, on the other hand, are designed to manage comorbidities associated with patients on maintenance dialysis, to tailor the ultrafiltration profile based upon dwell time, and to better preserve peritoneal membrane function and host defenses. The evidence to date indicates that, in malnourished PD patients (children and adults), IP amino acids improve protein nutritional status, particularly if low protein intakes are a cause of the malnutrition. The availability of glucose polymers allows the clinician to complement standard glucose-based formulations with one that can provide improved ultrafiltration in both CAPD and APD patients for long dwells, and in patients experiencing ultrafiltration loss owing to a large effective peritoneal surface area. Owing to the reduced calorie and carbohydrate load, glucose polymers may also offer long-term metabolic advantages. Although the control of acid-base balance can be well managed in the vast majority of patients with a 35-40 mmol/L lactate solution, the development and clinical evaluation of bicarbonate-based solutions is underway as a result of concern over the potentially bioincompatible nature of acidic lactate formulations. To date, in vitro, ex vivo, and limited clinical studies show that such formulations, and in particular bicarbonate/lactate combinations are efficacious and well tolerated, and show improved peritoneal cell function versus conventional solutions. In conclusion, ongoing research and development has produced a new generation of PD solutions that, to various degrees, meet different criteria established for an ideal PD solution for chronic adult and pediatric patients on PD. These criteria include good clearance and ultrafiltration, supply of nutrition, iso-osmolality, physiologic pH, bicarbonate buffer, and minimal absorption of the osmotic agent. Several of the new solutions have already demonstrated clinical utility in controlled clinical trials and are commercially available in Europe. Wider clinical use will further add to our understanding of the impact of these formulations on patient outcomes.

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 (C) 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-base 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.

Bicarbonate and bicarbonate/lactate peritoneal dialysis solutions for the treatment of infusion pain.

A randomized, double-blind, cross-over study was undertaken to determine the effects of novel bicarbonate (38 mM) and bicarbonate (25 mM)/lactate (15 mM) containing peritoneal dialysis (PD) solutions on infusion pain in patients who experienced inflow pain with conventional lactate (40 mM) solution. Pain was assessed using a verbal rating scale and the validated McGill Pain Questionnaire (MPQ). Eighteen patients were recruited to the study. Both novel solutions resulted in highly statistically significant reductions in inflow pain compared to the control lactate solution, as assessed with both the verbal rating scale and the MPQ. For all pain variables assessed, the bicarbonate/lactate solution was more effective than the bicarbonate solution in alleviating pain. In conclusion, both solutions reduced the infusion pain experienced with control solution, but the bicarbonate/lactate solution appears to be the most effective. In contrast to the most widespread current treatment, which is the manual injection of sodium bicarbonate, the bicarbonate/lactate solution does not have the associated increased risk of peritonitis.

Clinical evaluation of a peritoneal dialysis solution with 33 mmol/L bicarbonate.

OBJECTIVE: To evaluate the efficacy and safety of a new peritoneal dialysis solution with 33 mmol/L bicarbonate. DESIGN: In an acute, prospective, randomized cross-over study, 8 patients were randomized in two groups of 4. On the first study day, the first group performed two consecutive 4-hour exchanges with a dialysis solution containing 35 mmol/L lactate: the first exchange with 13.6 g/L and the second with 38.6 g/L dextrose. On the second study day, the same type of exchanges were performed with bicarbonate. The second group underwent the same treatment, but used bicarbonate solutions on the first day and control solutions on the second study day. Thirty-three patients participated in a 2-month prospective and randomized study. After a 4-week baseline period using solutions containing 40 mmol/L lactate, the patients were dialyzed with either 33 mmol/L bicarbonate solutions or 40 mmol/L lactate solutions. SETTING: Peritoneal dialysis units at the University Hospital of Brescia and the Niguarda Hospital of Milan, Italy. RESULTS: Acute study: Control and bicarbonate solutions had similar effects on blood chemistries and peritoneal transport. Chronic study: Mean venous bicarbonate concentrations remained unchanged in the control group (26.6-27.2 mmol/L), but decreased significantly in the bicarbonate group from 28.8 mmol/L at the start of the study to 23.0 mmol/L after 2 months of bicarbonate administration. Other biochemical parameters remained unchanged. CONCLUSION: A peritoneal dialysis solution with a bicarbonate level of 33 mmol/L does not adequately correct uremic acidosis.

A randomized controlled trial of a bicarbonate- and a bicarbonate/lactate-containing dialysis solution in CAPD.

OBJECTIVE: To evaluate the safety and efficacy of bicarbonate- and bicarbonate/lactate-based PD fluids. DESIGN: A randomly allocated prospective controlled trial lasting eight weeks. SETTING: Five renal units in Europe. PATIENTS: Individuals who have been treated by CAPD for at least three months and who have had at least one month's therapy with 40 mmol/L lactate PD fluid. Those with recent infection, diabetes or other serious illness are excluded. Forty-seven individuals have entered the study so far. INTERVENTIONS: Patients are randomly allocated to three groups. Group 1 receive 40 mmol/L lactate dialysate, Group 2 are given 38 mmol/L bicarbonate fluid and Group 3 are tested with a 25 mmol/L bicarbonate and 15 mmol/L lactate dialysate. OUTCOME MEASURES: The primary outcome measure is the plasma bicarbonate level. Adverse events and ease of use of the two-chambered bags used by Groups 2 and 3 are also being assessed. RESULTS: To date, plasma bicarbonate levels have been the same in all treatment groups up to the end of the trial period. There are no differences in serum lactate levels. No side effects are attributable to the test fluids. The patients have managed the two-chambered bags successfully. CONCLUSION: This trial is still ongoing, but to date, neutral bicarbonate based fluids have been as effective as lactate dialysate in treating uremic acidosis.

Reduced risk for peritonitis in CAPD with the use of a UV connector box.

A common route for peritoneal infection is the bag transfer connecting site. To investigate possible reduction of such transfer infections with the use of a bag transfer set (UV-XD, Travenol, Baxter, Minneapolis), this study sampled patients using a transfer set with or without UV light sterilization. Calculations excluded peritonitis due to penetrating tunnel infection or defective peritoneal dialysis bag (4 episodes in 2 patients). The study included 51 patients with a median age of 62 years (range 25-81). Five were switched from manual connection (Travenol, Type II) to UV-XD, and each suffered from at least 2 peritonitis episodes during 9-24.5 months prior to the change to UV-XD. In this patient group, the incidence of peritonitis fell significantly from 1 peritonitis/4 to 1/21 months. The bag transfer set was used without UV light in 35 patients for a total of 178 months, producing an incidence of 1 episode/7.7 treatment months. These patients had significantly more peritonitis than 35 patients who used the UV light for a total of 416 months (1 episode/21 months). In 19 patients who used both techniques, there was less risk for peritonitis when UV light was used (p = 0.001). We conclude that the UV-XD device is simple to handle and may reduce the incidence of peritonitis, especially if the box is used in tandem with UV light sterilization.

Design and testing of the Baxter Integrated Disconnect Systems (IDS).

This paper describes the result of a miltidisciplinary approach to the design and evaluation of a new CAPD disconnect system: the Baxter Integrated Disconnect System (IDS). This system consists of a bag full of fresh Dianeal, an empty bag for the drainage of spent dialysate and tubings connecting the 2 in a Y fashion. With this system, the patient makes only one connection. The system is disposable. The major property that makes this unique is that all components are preassembled, and the whole system is steam-sterilized as 1 unit. In general, similar systems use different sterilization methods for the various components of the system. Those components are then assembled, under clean conditions by the manufacturer, without final sterilization of the unit. Assembly of the components is sometimes left to the patient. The concept of IDS, therefore, is unique and warrants lower rates of contamination. This system has been tested on patients for a total observation period of 765 patient months, and has proven to be simple, safe and effective. It yields a 63% probability of peritonitis-free patients at 24 months.

Peritoneal transport in CAPD patients with permanent loss of ultrafiltration capacity.

During a 10 year period, 14 out of 227 patients (6.2%) undergoing continuous ambulatory peritoneal dialysis (CAPD) developed permanent loss of ultrafiltration capacity (UFC). The risk of UFC loss increased from 2.6% after one year to 30.9% after six years of treatment. A six hour, single dwell study with glucose 3.86% dialysis fluid was carried out in nine of the UFC loss patients and in 18 CAPD patients with normal UFC. Intraperitoneal dialysate volumes were calculated using 131I-tagged albumin (RISA) as volume marker with a correction applied for its elimination from the peritoneal cavity. The RISA elimination coefficient (KE), which can serve as an estimation of the upper limit of the lymphatic flow, was also calculated. Diffusive mass transport coefficients (KBD) for investigated solutes (glucose, creatinine, urea, potassium, total protein, albumin and beta 2-microglobulin) were calculated during a period of dialysate isovolemia. Two patterns of UFC loss were observed: (a) seven patients had high KBD values for small solutes resulting in rapid uptake of glucose, whereas KBD values for proteins were normal; (b) two patients had normal KBD values but a threefold increase both in the fluid reabsorption rate and KE. We conclude that loss of the osmotic driving force (due to increased diffusive mass transport for small solutes) and increased fluid reabsorption (possibly due to increased lymphatic reabsorption) are the two major causes of permanent loss of UFC in CAPD patients.

Diverticular disease of the colon: a risk factor for peritonitis in continuous peritoneal dialysis.

To study the possible influence of colonic diverticula on the risk of peritonitis of enteral (intestinal) origin in patients undergoing continuous peritoneal dialysis, a barium enema was carried out as a pretreatment investigation in 129 consecutive patients starting CAPD over a 9-year period. In this prospective study comprising 3103 patient months, a total of 44 (15% of all) episodes of peritonitis with micro-organisms of enteral origin occurred in 30 of the 129 patients. The estimated probability of developing such an episode was 16% and 24%, respectively, within 1 or 2 years of treatment. Diverticula (greater than or equal to 1) were found in 54 (42%) of all patients. In all cases the following factors: greater than or equal to 10 diverticula, diverticular size of greater than or equal to 10 mm and diverticula in the ascending, transverse, or descending colon, significantly increased the risk of developing peritonitis of enteral origin (P less than 0.05). Neither diverticula in the sigmoid colon nor diverticulitis, as assessed by radiological findings, were identified as risk factors. Enteral episodes (as defined in this study) appear to represent mainly microperformations of existing diverticula; such episodes should probably be regarded as and handled differently from episodes due to major perforations of the colon secondary to diverticulitis. We conclude that diverticular disease of the non-sigmoid colon is a risk factor for peritonitis in CAPD.

Peritonitis in continuous ambulatory peritoneal dialysis (CAPD): diagnostic findings, therapeutic outcome and complications.

The analysis of all episodes of peritonitis occurring in a uniformly treated continuous ambulatory peritoneal dialysis (CAPD) population (N = 128) at one centre during a six-year period showed the following major findings. The initial white cell count (WCC) of the dialysate was less than 100 x 10(6)/L in 10% of the episodes and showed a predominance of mononuclear cells in 15%. The Gram stain results were consistent with the findings of the culture in 28% of the episodes and influenced the initial therapy in only 7% of the cases. Between 9% and 31% of all episodes would not have been classified as peritonitis if positive culture, a WCC of greater than 100 x 10(6)/L in the dialysate, or clinical symptoms had been required for the diagnosis. The proportion of negative dialysate cultures was 2% after the introduction of pre-culture membrane filtration. Tunnel infection as a cause of peritonitis was more frequent in episodes due to Staphylococcus aureus than in episodes due to coagulase-negative staphylococci (p = 0.009). Peritonitis caused by coagulase negative staphylococci were followed by a milder course than other organisms (p = 0.02). Of all episodes initially treated with cephradine only 62% were cured with this antibiotic (or cloxacillin) and 35% were followed by recurrency, protracted course or catheter loss, despite intermediate or full in vitro susceptibility. In only 53% of all episodes no complication was observed. Complications were more frequent in women and diabetics than in men (p = 0.01) and non-diabetics (p = 0.03), and were more common in episodes with clinical symptoms (p = 0.02). Peritonitis resulted in drop-out from CAPD in 6% of all episodes. Hospital care was needed in 68% of all episodes. We conclude that turbidity can be used as the sole criterion for the initial diagnosis of peritonitis, and that a first generation cephalosporin should not be used as a first line antibiotic in the treatment of CAPD peritonitis.