IMPROVED IN VITRO BIOCOMPATIBILITY OF BICARBONATE BUFFERED PERITONEAL DIALYSIS FLUID (original) (raw)
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Kidney International, 1998
Biocompatibility and buffers: Effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function. Background. Conventional peritoneal dialysis fluids (PDF) have been shown to compromise the function of both leukocytes and human peritoneal mesothelial cells (HPMC). Various in vitro studies have identified the low initial pH in combination with high lactate content, as well as the hyperosmolality and high glucose concentration present in currently used solutions as the primary determinants of their bioincompatibility. Bicarbonate buffered PDF (at neutral pH) display improved in vitro biocompatibility as compared to conventional, lactate buffered PDF. However, little information is currently available regarding the potential impact of PDF on the function of human peritoneal fibroblasts (HPFB), the major cell population present in peritoneal interstitium. Methods. The current study compares the effect of bicarbonate and lactate buffered PDF in a model system of resting peritoneal mesothelial cells and fibroblasts cultured from human omentum. Interleukin-1-stimulated IL-6 release from HPMC and HPFB was used as the cell functional parameter. Results. While short (30 min) pre-exposure to lactate buffered PDF significantly reduced the IL-1-stimulated IL-6 release from HPMC during a subsequent recovery period (24 hr), a significant decrease in HPMC IL-6 secretion with bicarbonate buffered PDF was only observed after prolonged (Ն60 min) exposure. In contrast, no significant IL-6 inhibition was detected with HPFB pre-exposed to PDF for up to 90 minutes. A significant suppression of HPFB IL-6 secretion was only observed in coincubation experiments (24 hr) with dilutions of both types of PDF. Conclusions. These results indicate that (i) bicarbonate buffered PDF are less inhibitory to peritoneal cell function as compared to conventional, lactate buffered PDF; and (ii) HPFB may be more resistant than HPMC to bioincompatible PDF.
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.
Kidney International, 1996
Biocompatibility of bicarbonate buffered peritoneal dialysis fluids: Influence on mesothelial cell and neutrophil function. The present study compares the effects of lactate and bicarbonate buffered PDF on human neutrophil (PMN) and human peritoneal mesothelial cell (HPMC) viability and function. Acute exposure of PMN to lactate buffered PDF at pH 5.5 (CAPD 2, 1.5% and CAPD 3, 4.25% glucose) resulted in significant reductions in cellular ATP levels, the phagocytosis of serum treated zymosan (STZ) and respiratory burst activation (CL). Exposure of PMN to bicarbonate buffered PDF (BIC 20, 1.5% glucose and BIC 30, 4.25% glucose both at pH 7.2) had no significant effect on cell viability or the CL response. Phagocytosis was, however, depressed significantly more following exposure to BIC 30 than BIC 20. PMN cellular ATP levels and phagocytosis were significantly better in cells exposed to BIC 30 than to CAPD 3 at pH 7.4 (P = 0.043 for both). Pre-exposure of HPMC to CAPD 2, CAPD 3 or BIC 30 for 30 minutes resulted in a significant reduction in cellular ATP content compared to control medium. Pre-exposure to BIC 20 did not result in a reduction in HPMC ATP levels. HPMC synthesis of IL-6 was unaffected by 15 or 30 minutes pre-exposure to BIC 20 or BIC 30, in contrast pre-exposure to CAPD 2 or CAFD 3 for 15 or 30 minutes resulted in a significant reduction in stimulated IL-6 synthesis (24.5 3.01 and 32.3 5.0 vs. 43.9 10 pg/.rg cell protein in M199, N 6; P = 0.02). Neutralization of the pH of CAPD 2 and CAPD 3 resulted in normalization of HPMC JL-6 secretion. Analysis of IL-6 mRNA expression in control, BIC 20 and 30 pre-treated HPMC subsequently stimulated with IL-1 revealed no differences in the expression of the IL-6 specific 465 base pair transcripts. The improved cellular function in bicarbonate buffered PDF indicates potentially improved host defence status and preservation of the peritoneal membrane in CAPD patients. Peritoneal dialysis has been used as a therapy for end-stage renal failure for more than twenty years. During this period significant advances have been made in reducing the rate of infection, mainly as a result of improvements in delivery systems [1, 2]. During this same period, however, despite significant evidence to indicate its bioincompatibility, the almost exclusive use of lactate-buffered peritoneal dialysis fluid (PDF) has continued. Only relatively recently have alternative dialysis fluids become available for clinical trials. It is now well established that lactate-buffered peritoneal dial
Journal of the American Society of Nephrology, 2003
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 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.
BMC nephrology, 2004
Peritoneal dialysis (PD) is the preferred dialysis modality in children. Its major drawback is the limited technique survival due to infections and progressive ultrafiltration failure. Conventional PD solutions exert marked acute and chronic toxicity to local tissues. Prolonged exposure is associated with severe histopathological alterations including vasculopathy, neoangiogenesis, submesothelial fibrosis and a gradual loss of the mesothelial cell layer. Recently, more biocompatible PD solutions containing reduced amounts of toxic glucose degradation products (GDPs) and buffered at neutral pH have been introduced into clinical practice. These solutions contain lactate, bicarbonate or a combination of both as buffer substance. Increasing evidence from clinical trials in adults and children suggests that the new PD fluids may allow for better long-term preservation of peritoneal morphology and function. However, the relative importance of the buffer in neutral-pH, low-GDP fluids is st...