BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991] (original) (raw)
Related papers
Kidney International, 2002
influenced by pH-neutral PD fluid. Creatinine and phosphate Effects of pH-neutral, bicarbonate-buffered dialysis fluid on elimination appears to be slightly reduced with bicarbonate peritoneal transport kinetics in children. fluid; this observation awaits clarification in extended therapeu-Background. Due to their superior biocompatibility, pHtical trials. neutral solutions are beginning to replace acidic lactatebuffered 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 Conventional peritoneal dialysis (PD) solutions imionic shifts and initial peritoneal vasodilation. Such differences pair mesothelial and local macrophage cell functions due may become clinically relevant in patients with frequent short to their high concentrations of lactate and glucose, acidic cycles on automated PD (APD). Methods. Twenty-five children were treated with a lactatebuffering and the formation of toxic glucose degradation buffered (35 mmol/L, pH 5.5) or a bicarbonate-buffered PD products (GDP) during manufacturing [1]. GDPs and solution (34 mmol/L, pH 7.4) in randomized order on two lactate have been demonstrated to trigger the local resequential days. Each day a four-hour Standardized Permeabillease of growth factors such as vascular endothelial ity Analysis (SPA) was performed, followed by overnight APD growth factor (VEGF) and transforming growth factor- (7 cycles, fill volume 1000 mL/m 2 , dwell time 75 min). Functional peritoneal surface area was dynamically assessed using (TGF-), which are potent stimulators of neoangiogenthe three-pore model. esis and fibrogenic processes [2-6]. These mechanisms Results. While intraperitoneal pH was constant at 7.41 Ϯ are believed to contribute to peritoneal sclerosis and loss 0.03 throughout the SPA with bicarbonate fluid, the dialysate of ultrafiltration, major causes of long-term PD failure remained acidic for more than one hour with lactate solution (pH 7.12 Ϯ 0.08 at 1 h). Total pore area was 60% higher [7-9]. during the first 30 minutes of the dwell than under steady-state Bicarbonate-based PD solutions are buffered at neuconditions, without a difference between acidic and pH-neutral tral pH and virtually free of GDPs [10]. The superior fluid. Net base gain, intraperitoneal volume kinetics, glucose biocompatibility of pH neutral solutions has been demabsorption, ultrafiltration rate, effective lymphatic absorption onstrated in numerous in vitro studies [11-16]. Recent and the transport of urea, potassium,  2-microglobulin and albumin were similar with both fluids. However, phosphate technological advances have solved the problem of bicarand creatinine elimination were 10% lower with bicarbonate bonate stability, permitting the routine use of these solu-PD fluid, resulting in corresponding significant decreases in tions in chronic PD [10]. the 24-hour clearances of these solutes. The instillation of fresh, lactate-based PD fluid leads Conclusion. The peritoneal surface area is not measurably to a marked initial dilatation of peritoneal capillaries, resulting in a transient increase of the peritoneal surface 1 The authors are members of the Mideuropean Pediatric Peritoneal area available for solute transfer in the early phase of Dialysis Study Group (MEPPS). the dwell period [17]. Experimental studies have suggested that the low pH of conventional lactate-buffered
Nephrology Dialysis Transplantation, 2006
Background. Chronic utilization of a bio-incompatible peritoneal dialysis (PD) solution with acidic pH and a high content of glucose degradation product (GDP) has been implicated as a contributing cause of peritoneal failure. We compared a newly formulated solution of neutral pH and low levels of GDP to a standard PD solution. Methods. Fifty new PD patients were randomized to a conventional lactate-buffered fluid (control) and a pH neutral, lactate-buffered, low GDP solution (balance). Patients were followed for 12 months. Serum samples were assayed for C-reactive protein (CRP). PD effluent was collected and assayed for cancer antigen-125 (CA125) and hyaluronan (HA). Clinical end points were the residual renal function and dialysis adequacy indices. Results. After 52 weeks of treatment, PD fluid CA125 rose from 2.45 AE 0.96 to 14.30 AE 2.17 U/ml (P < 0.001), and HA declined from 2.26 AE 0.60 to 1.45 AE 0.32 mg/ml (P ¼ 0.07) in the balance group. The balance group had a higher PD fluid CA-125 (14.30 AE 2.17 vs 7.36 AE 2.23 U/ml, P ¼ 0.007), lower HA (1.45 AE 0.32 vs 2.55 AE 0.32 mg/ml, P ¼ 0.007), and lower serum CRP level (1.77 AE 0.42 vs 7.73 AE 2.42 mg/l, P ¼ 0.026) than the control group at 52 weeks. There was no difference in dialysis adequacy indices, ultrafiltration volume, urine output, residual renal function, peritonitis rate or need of hospitalization in 1 year. Conclusion. As compared to conventional PD solution, the use of balance, a neutral pH, low GDP solution resulted in a superior profile of PDE mesothelial cell marker and a lower degree of systemic inflammation, and the difference was maintained for 1 year.
Biocompatibility and tolerability of a purely bicarbonate-buffered peritoneal dialysis solution
Peritoneal Dialysis …, 2009
Hyaluronic acid levels were significantly lower after the use of bicPDF (185.0 ± 119.6 ng/mL) than after SPDF (257.4 ± 174.0 ng/mL, p = 0.013). Both TNF-α α α α α and TGF-β β β β β1 showed higher levels with the use of bicPDF than with SPDF. No differences were observed for IL-6, VEGF, or IFNγ γ γ γ γ levels. We observed an improvement in the glomerular filtration rate with the use of bicPDF but no differences were observed for total fluid loss. Pain scores could be analyzed in 23 patients: there was no difference between the solutions. ♦ ♦ ♦ ♦ ♦ Conclusions: The use of a purely bicarbonate-buffered low-glucose degradation product solution significantly changes most of the peritoneal effluent markers measured, suggesting an improvement in peritoneal membrane integrity. Additionally, it seems to have a positive effect on residual renal function.
Use of new peritoneal dialysis solutions in children
Kidney International, 2008
Standard peritoneal dialysis (PD) solutions with low pH and containing high concentrations of lactate and glucose have been demonstrated to negatively affect the peritoneal membrane, mesothelial cell viability, residential peritoneal cells, and also to inhibit phagocytic functions. An increasing body of experimental evidence supports the idea that the peritoneal hypervascularization and fibrosis observed in long-term PD are causally related to the acute and chronic toxicity of conventional PD solutions. A Physioneal (lactate/ bicarbonate mixed buffer pH 7-7.4), Physioneal, Extraneal (7.5% icodextrin), Nutrineal (1.1% amino-acid-containing solution) regimen, for example, offers a significant reduction in carbohydrate load (approximately 40-50%), lower exposure to and absorption of glucose degradation products, reduced oxidative stress, and improved volume control when compared with a first-generation DDDD (4 Â Dianeal) regimen. The positive aspects of each solution that we have observed in our patients allow a recommendation on the potential benefit of using these solutions in children treated with PD. In fact, data from the literature as well as the results of the studies reported in this paper show that in children the application of neutral pH bicarbonate/lactate-buffered solution for the standard nighttime APD prescription, icodextrin solution for a long daytime dwell, and AA-based solution in malnourished patients is safe and effective. Extended clinical trials should be encouraged to better define the PD schedules for the combined use of these solutions that may be associated with the best clinical efficacy and the highest level of biocompatibility.
Nephrology Dialysis Transplantation, 2009
Background. This study was designed to compare the effects of a conventional lactate-based peritoneal dialysis (PD) solution (D) and a new biocompatible bicarbonate/lactate-based solution with a low concentration of glucose degradation products (P) on peritoneal ultrafiltration (UF) and other peritoneal membrane indices. Methods. Twenty-six stable, prevalent PD patients were enrolled in this prospective study. They sequentially underwent 3 months of therapy with the D solution and 3 months with the P solution in a randomized order. Daily, overnight and 4-h UF on PET were measured and other peritoneal membrane indices were also assessed using PET with 2.27% glucose solution. Results. Twenty-one patients successfully completed the study. The mean daily peritoneal UF with D was 1324 ± 602 ml and 881 ± 633 ml with P (P < 0.001) and this
Biocompatibility of new peritoneal dialysis solutions: what can we hope to achieve?
2000
Despite the bioincompatibility of the "old", standard, high glucose, lactate-buffered peritoneal dialysis (PD) solutions, PD is itself a highly successful dialysis modality with patient survival equivalent to that of hemodialysis (HD) during the initial 3-5 years of dialysis therapy. Nevertheless, PD technique survival is often limited by infectious complications and alterations in the structure and function of the peritoneal membrane. These local changes also have a negative impact on patient survival owing to systemic effects such as those often seen in patients with high peritoneal transport rate and loss of ultrafiltration (UF) capacity. Patient mortality remains unacceptably high in both HD and PD patients, with most premature deaths being associated with signs of malnutrition, inflammation, and atherosclerotic cardiovascular disease (MIA syndrome). These systemic signs are likely to be influenced by PD solutions both directly and indirectly (via changes in the peritoneal membrane). New, biocompatible PD solutions may have favorable local effects (viability and function of the peritoneal membrane) and systemic effects (for example, on MIA syndrome). Amino acid-based solution [Nutrineal (N): Baxter Healthcare Corporation, Deerfield, IL, U.S.A.] may improve nutritional status as well as peritoneal membrane viability. Bicarbonate/lactate-buffered solution [Physioneal (P): Baxter Healthcare Corporation] may ameliorate local and systemic effects of low pH, high lactate, and high glucose degradation products. Icodextrin-based solution [Extraneal (E): Baxter Healthcare SA, Castlebar, Ireland] may improve hypertension and cardiovascular problems associated with fluid overload and may extend time on therapy in patients with loss of UF capacity. The positive effects of each of these new, biocompatible solutions have been demonstrated in several studies. It is likely that the combined use of N, P, and E solutions will produce favorable synergies in regard to both local effects (peritoneal viability) and systemic effects (less malnutrition, inflammation, and fluid overload). Solution combination is an exciting area for clinical study in the coming years. Furthermore, dialysis fluid additives such as hyaluronan, which protects and improves the function of the peritoneal membrane, may further improve PD solutions. The new, biocompatible PD solutions represent an entirely new era in the evolution of the PD therapy; they are likely to have markedly positive effects on both PD technique and PD patient survival in coming years.