Improved Acidosis Correction and Recovery of Mesothelial Cell Mass with Neutral-pH Bicarbonate Dialysis Solution among Children Undergoing Automated Peritoneal Dialysis SUSANNE HAAS,* CLAUS PETER SCHMITT,* KLAUS ARBEITER, † KLAUS-EUGEN BONZEL, ‡ MICHEL FISCHBACH, § ULRIKE JOHN,  ANNE-KATHRIN PIEPER, ¶ THOMAS PATRICK SCHAUB, # JUTTA PASSLICK-DEETJEN, # OTTO MEHLS,* and FRANZ SCHAEFER,* FOR THE MID EUROPEAN PEDIATRIC PERITONEAL DIALYSIS STUDY GROUP *Children’s Hospital, University of Heidelberg, Heidelberg, Germany; † Children’s Hospital, University of Vienna, Vienna, Austria; ‡ Children’s Hospital, University of Essen, Essen, Germany; § Hautepierre Hospital, University of Strasbourg, Strasbourg, France;  Children’s Hospital, University of Jena, Jena, Germany; ¶ Charité Children’s Hospital, Humboldt University, Berlin, Germany; and #Fresenius Medical Care, Bad Homburg, Germany. Abstract. Acid-base balance and peritoneal membrane longev- ity 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 bio- compatible, 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 ran- domized, prospective, crossover comparison with conven- tional, 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 bicar- bonate 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 in- creased blood pH during bicarbonate APD. Peritoneal equili- bration tests revealed subtle changes in solute transport, with a less steep creatinine equilibration curve during bicarbonate dialysis, suggesting reduced peritoneal vasodilation. The peri- toneal 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, bicar- bonate-buffered PD fluid provides more effective correction of metabolic acidosis and better preservation of peritoneal cell mass than do conventional, acidic, lactate-based fluids. Irreversible technique failure remains the major drawback of peritoneal dialysis (PD). Fifty percent of adult and pediatric patients undergoing PD must switch to hemodialysis within 4 to 5 yr (1,2). The incidence of PD failure attributable to infectious complications is steadily decreasing, because of major advances in the prevention and treatment of catheter- related infections, and loss of ultrafiltration and peritoneal sclerosis attributable to noninfectious mechanisms are becom- ing the leading causes of nonelective termination of PD (1). An increasing body of experimental evidence supports the idea that the peritoneal hypervascularization and fibrosis ob- served in long-term PD are causally related to the acute and chronic toxicity of conventional PD solutions (3,4). Low pH, high lactate levels, and hyperosmolar glucose contents inde- pendently impair mesothelial cell functions (5– 8). The pH of the dialysis fluid might be particularly relevant for automated PD (APD), in which frequent short cycles continuously expose the peritoneal membrane to a cytotoxic acidic milieu (9). Lactate may compromise local cell functions independently of pH by affecting the cellular redox state and reducing cellular energy sources. Furthermore, toxic glucose degradation prod- ucts are formed during heat sterilization of conventional PD solutions. Glucose degradation products are mostly devoid of acute cytotoxicity but impair the viability and functional in- tegrity of mesothelial cells during extended exposure (10). Received March 24, 2003. Accepted June 27, 2003. Correspondence to Dr. Franz Schaefer, Division of Pediatric Nephrology, University Children’s Hospital, Im Neuenheimer Feld 151, 69120 Heidelberg, Germany. Phone: +49-6221-56-32396; Fax: +49-6221-56-4203; E-mail: franz_schaefer@med.uni-heidelberg.de 1046-6673/1410-2632 Journal of the American Society of Nephrology Copyright © 2003 by the American Society of Nephrology DOI: 10.1097/01.ASN.0000086475.83211.DF J Am Soc Nephrol 14: 2632–2638, 2003