Use of new peritoneal dialysis solutions in children
2008; Elsevier BV; Volume: 73; Linguagem: Inglês
10.1038/sj.ki.5002615
ISSN1523-1755
AutoresA. Canepa, Enrico Verrina, Francesco Perfumo,
Tópico(s)Vitamin C and Antioxidants Research
ResumoStandard 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 × 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. 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 × 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. 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.1.Witowski J. Topley N. Jorres A. et al.Effect of lactate-buffered peritoneal dialysis fluids on human peritoneal mesothelial cell interleukin-6 and prostaglandin synthesis.Kidney Int. 1995; 47: 282-293Abstract Full Text PDF PubMed Scopus (101) Google Scholar, 2.Davies S.J. Phillips L. Naish P.F. et al.Peritoneal glucose exposure and changes in membrane solute transport with time on peritoneal dialysis.J Am Soc Nephrol. 2001; 12: 1046-1051PubMed Google Scholar, 3.Krediet R.T. Lindholm B. Rippe B. Pathophysiology of peritoneal membrane failure.Perit Dial Int. 2000; 20: S22-S42PubMed Google Scholar, 4.Yanez-Mo M. Larra-Pezzi E. Selgas R. et al.Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells.N Engl J Med. 2003; 348: 403-413Crossref PubMed Scopus (619) Google Scholar, 5.Topley N. Kaur D. Petersen M.M. et al.In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.J Am Soc Nephrol. 1996; 7: 218-224PubMed Google Scholar 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.6.Williams J.D. Craig K.J. Topley N. et al.Peritoneal dialysis: changes to the structure of the peritoneal membrane and potential for biocompatible solutions.Kidney Int. 2003; 63: S158-S161Abstract Full Text Full Text PDF Scopus (71) Google Scholar,7.Ha H. Cha M.K. Choi H.N. et al.Effects of peritoneal dialysis solutions on the secretion of growth factors and extracellular matrix proteins by human peritoneal mesothelial cells.Perit Dial Int. 2002; 22: 171-177PubMed Google Scholar Metabolic and cardiovascular burden arising from many sources, including glucose degradation products,8.Witowski J. Jörres A. Ksiazek K. et al.Glucose degradation products in peritoneal dialysis fluids: do they harm?.Kidney Int. 2003; 63: S148-S151Abstract Full Text Full Text PDF Scopus (45) Google Scholar vascular volume control,9.Williams J.D. Topley N. Craig K.J. et al.The Euro-Balance trial: the effect of new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane.Kidney Int. 2004; 66: 408-418Abstract Full Text Full Text PDF PubMed Scopus (342) Google Scholar oxidative stress,10.Monnier L. Mas E. Ginet C. et al.Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes.JAMA. 2006; 295: 1681-1687Crossref PubMed Scopus (1847) Google Scholar and glucose load11.Delarue J. Maingourd C. Couet C. et al.Effects of oral glucose on intermediary metabolism in continuous ambulatory peritoneal dialysis patients versus healthy patients.Perit Dial Int. 1998; 18: 505-511PubMed Google Scholar have been implicated in exacerbating the decline of residual renal function, a major determinant of patient outcome12.Bargman J.M. Thorpe K.E. Churchill D.N. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA Study.J Am Soc Nephrol. 2001; 12: 2158-2162Crossref PubMed Google Scholar that strongly influences morbidity and mortality of PD patients.13.Chung S.H. Beimbürger O. Stenvinkel P. et al.Association between residual renal function, inflammation and patient survival in new peritoneal dialysis patients.Nephrol Dial Transplant. 2003; 18: 590-597Crossref PubMed Scopus (149) Google Scholar The development of second generation PD solutions such as Extraneal (7.5% icodextrin) is expected to reduce these disease implications due to increased biocompatibility, removal of glucose, and reduced GDP.14.Cooker L.A. Holmes C.J. Hoff C.M. Biocompatibility of icodextrin.Kidney Int. 2002; 62: S34-S45Abstract Full Text Full Text PDF Scopus (38) Google Scholar A Physioneal (lactate/bicarbonate mixed buffer pH 7–7.4), Physioneal, Extraneal, 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 GDPs, reduced oxidative stress, and improved volume control when compared with a first-generation DDDD (4 × Dianeal) regimen.15.Holmes C.J. Shockley T.R. Strategies to reduce glucose exposure in peritoneal dialysis patients.Perit Dial Int. 2000; 20: S37-S41PubMed Google Scholar The nighttime automated peritoneal dialysis (APD) regimes with short cycles fit in well with the characteristics of the peritoneal membrane transport in children. The preference for APD as the dialytic treatment of choice for children with end-stage renal failure has also largely been a lifestyle choice; indeed, the nighttime APD courses enable children to attend school full time and reduce the impact of the dialysis treatment on the way of life of the patients and their families. Moreover, thanks to the wide range of treatment options available, APD can provide a dialytic schedule, which is tailored to the needs of children of different ages and body sizes. Therefore, during the last decade, APD has progressively replaced continuous ambulatory PD in the pediatric dialysis centers and is nowadays considered the chronic PD modality of choice for pediatric patients.16.Lerner G.R. Warady B.A. Sullivan E.K. et al.Chronic dialysis in children and adolescents. The 1996 annual report of the North American Pediatric Renal Transplant Cooperative Study.Pediatr Nephrol. 1999; 13: 404-417Crossref PubMed Scopus (104) Google Scholar,17.Verrina E. Edefonti A. Gianoglio B. et al.A multicenter experience on patients and technique survival in children on chronic dialysis.Pediatr Nephrol. 2004; 19: 82-90Crossref PubMed Scopus (71) Google Scholar Children represent the patient category that may potentially benefit most from the new, more physiological, high ultrafiltration (UF), and nutritive PD solutions, especially if one considers their long-term dependence on a functioning peritoneal membrane in case of a kidney transplant failure and the fact that in APD frequent short cycles continuously expose the peritoneal membrane to a non-physiological and bio-incompatible milieu. There is limited experience of the use of biocompatible PD solutions in children,18.Haas S. Schmitt C.P. Arbeiter K. et al.Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis.J Am Soc Nephrol. 2003; 14: 2632-2638Crossref PubMed Scopus (96) Google Scholar, 19.Vande Walle J. Raes A. Castillo D. et al.Advantages of HCO3 solution with low sodium concentration over standard lactate solutions for acute peritoneal dialysis.Adv Perit Dial. 1997; 13: 179-182PubMed Google Scholar, 20.Canepa A. Verrina E. Trivelli A. et al.Comparison of peritoneal amino acid (aa) losses in children on automatized peritoneal dialysis (apd) using lactate or bicarbonate/lactate-based solutions.Pediatr Nephrol. 2000; 14: C94Google Scholar, 21.Fischbach M. Terzic J. Chauvé S. et al.Effect of peritoneal dialysis fluid composition on peritoneal area available for exchange in children.Nephrol Dial Transplant. 2004; 19: 925-932Crossref PubMed Scopus (41) Google Scholar, 22.Schmitt C.P. Haraldsson B. Doetschmann R. et al.Effects of pH-neutral, bicarbonate-buffered dialysis fluid on peritoneal transport kinetics in children.Kidney Int. 2002; 61: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar and it is reported in a variety of pediatric centers. Our goal of this study was to present a brief overview of what has been published so far in this area of pediatric nephrology and, more important, to report our own experience with all three new generation PD solutions (Physioneal, Extraneal, and Nutrineal) in our pediatric population treated with PD at the Institute Gaslini in Genoa, Italy. Physioneal is a glucose-based PD solution buffered with bicarbonate/lactate, Extraneal has icodextrin as an osmotic agent, and Nutrineal has amino acids (AAs) as an osmotic agent. Both in vitro and ex vivo studies and, more recently also in vivo studies, with bicarbonate-buffered solutions have shown improvements in biocompatibility compared with lactate-buffered solutions.5.Topley N. Kaur D. Petersen M.M. et al.In vitro effects of bicarbonate and bicarbonate-lactate buffered peritoneal dialysis solutions on mesothelial and neutrophil function.J Am Soc Nephrol. 1996; 7: 218-224PubMed Google Scholar, 18.Haas S. Schmitt C.P. Arbeiter K. et al.Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis.J Am Soc Nephrol. 2003; 14: 2632-2638Crossref PubMed Scopus (96) Google Scholar, 23.Gotloib L. Wajsbrot V. Shostak A. et al.Population analysis of mesothelium in situ and in vivo exposed to bicarbonate-buffered peritoneal dialysis fluid.Nephron. 1996; 73: 219-227Crossref PubMed Scopus (25) Google Scholar, 24.Topley N. Kaur D. Petersen M.M. et al.Biocompatibility of bicarbonate buffered peritoneal dialysis fluids: influence on mesothelial cell and neutrophil function.Kidney Int. 1996; 49: 1447-1456Abstract Full Text PDF PubMed Scopus (96) Google Scholar, 25.Jones S. Holmes C.J. Mackenzie R.K. et al.Continuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.J Am Soc Nephrol. 2002; 13: S97-S103PubMed Google Scholar Biocompatibility, UF capacity, and correction of acidosis are three important features in the maintenance treatment of pediatric PD patients. Studies by Jones et al.25.Jones S. Holmes C.J. Mackenzie R.K. et al.Continuous dialysis with bicarbonate/lactate-buffered peritoneal dialysis fluids results in a long-term improvement in ex vivo peritoneal macrophage function.J Am Soc Nephrol. 2002; 13: S97-S103PubMed Google Scholar and Tranaeus26.Tranaeus A. A long-term study of a bicarbonate/lactate-based peritoneal dialysis solution—clinical benefits. The Bicarbonate/Lactate Study Group.Perit Dial Int. 2000; 20: 516-523Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar have demonstrated improved biocompatibility, UF capacity, and correction of acidosis in adult PD patients treated with bicarbonate/lactate-based PD solutions. Haas et al.18.Haas S. Schmitt C.P. Arbeiter K. et al.Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis.J Am Soc Nephrol. 2003; 14: 2632-2638Crossref PubMed Scopus (96) Google Scholar reported with a 34 mM bicarbonate solution (BicaVera 170/180/190; Fresenius Medical Care, Bad Homburg, Germany) an improved correction of acidosis with respect to a 35 mM lactate (pH 5.5, CAPD 17/18/19; Fresenius Medical Care), without important modifications in transport kinetics in children undergoing APD. Furthermore, the same authors reported that the peritoneal release of CA-125 increased twofold during bicarbonate APD, which is consistent with recovery of the mesothelial cell layer, indicating improved in vivo mesothelial cell tolerance to high-dose glucose with the neutral pH PD solutions containing reduced GDPs.18.Haas S. Schmitt C.P. Arbeiter K. et al.Improved acidosis correction and recovery of mesothelial cell mass with neutral-pH bicarbonate dialysis solution among children undergoing automated peritoneal dialysis.J Am Soc Nephrol. 2003; 14: 2632-2638Crossref PubMed Scopus (96) Google Scholar Fischbach et al., in a pilot study on the effect of PD fluid composition on peritoneal area available for exchange in children, suggest a higher biocompatibility for Physioneal than for Dianeal. They report that the less inflow pain associated with Physioneal induced a lower intraperitoneal pressure, reflecting enhanced fill volume tolerance, and a lower steady-state unrestricted area over diffusion distance reflected less capillary recruitment. They suggest that more biocompatible PD solutions will improve PD therapy, although this conclusion will require verification in extended clinical trials.21.Fischbach M. Terzic J. Chauvé S. et al.Effect of peritoneal dialysis fluid composition on peritoneal area available for exchange in children.Nephrol Dial Transplant. 2004; 19: 925-932Crossref PubMed Scopus (41) Google Scholar In our center, we have examined the peritoneal alkali mass balance and UF in children on APD treated with either lactate- or bicarbonate/lactate-buffered PD solutions. The aim of this study was to evaluate the effects of a combined 25 mmol l−1 bicarbonate/15 mmol l−1 lactate-based solution (Physioneal, Baxter SpA, Sesto Fiorentino, Italy) compared with a 40 mmol l−1 lactate-based solution (Dianeal PD4; Baxter Healthcare, Castlebar, Ireland) on the uptake of alkali. The second aim of this study was to investigate if the alkali uptake and UF could be comparable with this new more 'physiological,' that is, bicarbonate/lactate-based PD solution. Daily UF rates did not differ significantly between lactate or bicarbonate/lactate PD solutions (126.3±310 versus 152±359 ml), even if there was a tendency to increased UF with the bicarbonate/lactate PD solutions. The results of the peritoneal alkali mass balance are shown in Table 1 and Figure 1.Table 1Alkali peritoneal mass balance of the children on APD with lactate- or bicarbonate/lactate-based solutions (mean±s.d.)Dianeal PD4, mmol (lactate=40 mmol)Physioneal, mmol (lactate=15 mmol, HCO3=25 mmol)(Vi × LACTATEi)231.2±128.788.8±47.7***P<0.01(Vi × HCO3i)0148±79.5***P<0.01(Vi × LACTATEi)+(Vi × HCO3i)231.2±128.7236.8±127.2(Ve × LACTATEe)185.5±118.574±47.3***P<0.01(Ve × HCO3e)39.9±18.6149.1±74***P<0.01(Vi × HCO3i)-(Ve × HCO3e)-39.9±18.6-1.1±7.4**P<0.001.(Vi × LACTATEi)-(Ve × LACTATEe)45.7±14.614.8±2.9***P<0.01Mass balance5.77±16.513.68±9.6APD, automated peritoneal dialysis; HCO3e, bicarbonate concentration in the effluent; HCO3i, bicarbonate concentration in dialysis solution; LACTATEe, lactate concentration in the effluent; LACTATEi, lactate concentration in the dialysis solution; Ve, dialysate drained volume; Vi, dialysate infused volume.*P<0.05,** P<0.01*** P<0.001. Open table in a new tab APD, automated peritoneal dialysis; HCO3e, bicarbonate concentration in the effluent; HCO3i, bicarbonate concentration in dialysis solution; LACTATEe, lactate concentration in the effluent; LACTATEi, lactate concentration in the dialysis solution; Ve, dialysate drained volume; Vi, dialysate infused volume. *P<0.05, The amount of alkali infused was comparable with the two solutions: 231.2±128.7 mmol with lactate-based solution versus 236.8±127.2 mmol with bicarbonate/lactate-based solution. The lactate losses in the effluent were 185.5±118.5 mmol with lactate-based solution versus 74±47.3 mmol with bicarbonate/lactate-based solution; the difference may be explained by the different concentrations of lactate in the two PD solutions. The amount of lactate absorbed was 45.7±14.6 mmol with lactate-based solution versus 14.8±2.9 mmol with bicarbonate/lactate-based solution. The percentage of lactate absorbed of the infused amount was 19.7 with lactate-based solution versus 16.6 with bicarbonate/lactate-based solution. Bicarbonate losses in the effluent were 39.9±18.6 mmol with lactate-based solution versus 149.1±74 mmol with bicarbonate/lactate-based solution; the difference was due to the different concentrations of bicarbonate in the two solutions. The difference between bicarbonate infused and lost with the bicarbonate/lactate-based solution was -1.1±7.4 mmol, showing that there were no further losses with respect to the infused amount. The peritoneal alkali mass balance showed a slight, but not significant, increase to 13.68±9.6 versus 5.77±16.5 mmol with the bicarbonate/lactate-based solution. No side effects were observed that could be attributed to the tested PD solutions. In this study, we found a significant difference in lactate losses in the effluent with lactate- versus bicarbonate/lactate-based solution due to the different concentration of lactate in the two solutions (Table 1 and Figure 1). This difference reflects the fact that with lactate-buffered PD solutions the peritoneal cells are exposed to a much higher lactate concentration (and low pH) for a period of 8–10 h during the APD session. Indeed, it is known that with standard lactate PD solution the peritoneal membrane is exposed to an acidic environment for more than 1 h before peritoneal pH equilibration takes place.22.Schmitt C.P. Haraldsson B. Doetschmann R. et al.Effects of pH-neutral, bicarbonate-buffered dialysis fluid on peritoneal transport kinetics in children.Kidney Int. 2002; 61: 1527-1536Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Acidity and high lactate concentrations are one of the major inhibitory pathways by which conventional PD solutions modulate cell function.27.Liberek T. Topley N. Jörres A. et al.Peritoneal dialysis fluid inhibition of polymorphonuclear leukocyte respiratory burst activation is related to the lowering of intracellular pH.Nephron. 1993; 65: 260-265Crossref PubMed Scopus (118) Google Scholar
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