BIOKID: randomized controlled trial comparing bicarbonate and lactate buffer in biocompatible peritoneal dialysis solutions in children [ISRCTN81137991].
BACKGROUND
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 still unclear. In vitro, lactate is cytotoxic and vasoactive at the concentrations used in PD fluids. The BIOKID trial is designed to clarify the clinical significance of the buffer choice in biocompatible PD fluids.


METHODS
The objective of the study is to test the hypothesis that bicarbonate based PD solutions may allow for a better preservation of peritoneal transport characteristics in children than solutions containing lactate buffer. Secondary objectives are to assess any impact of the buffer system on acid-base status, peritoneal tissue integrity and the incidence and severity of peritonitis. After a run-in period of 2 months during which a targeted cohort of 60 patients is treated with a conventional, lactate buffered, acidic, GDP containing PD fluid, patients will be stratified according to residual renal function and type of phosphate binding medication and randomized to receive either the lactate-containing Balance solution or the bicarbonate-buffered Bicavera solution for a period of 10 months. Patients will be monitored by monthly physical and laboratory examinations. Peritoneal equilibration tests, 24-h dialysate and urine collections will be performed 4 times. Peritoneal biopsies will be obtained on occasion of intraabdominal surgery. Changes in small solute transport rates, markers of peritoneal tissue turnover in the effluent, acid-base status and peritonitis rates and severity will be analyzed.
Nau
Barbara
B
University Children's Hospital Heidelberg, Im Neuenheimer Feld 150, 69120 Heidelberg, Germany. barbara_nau@med.uni-heidelberg.de <barbara_nau@med.uni-heidelberg.de>
Schmitt
Claus P
CP
Almeida
Margarida
M
Arbeiter
Klaus
K
Ardissino
Gianluigi
G
Bonzel
Klaus E
KE
Edefonti
Alberto
A
Fischbach
Michel
M
Haluany
Karin
K
Misselwitz
Joachim
J
Kemper
Markus J
MJ
Rönnholm
Kai
K
Wygoda
Simone
S
Schaefer
Franz
F
D000293:Adolescent; D001639:Bicarbonates / Q000494:pharmacology*; D001672:Biocompatible Materials; D001692:Biological Transport / Q000187:drug effects; D002021:Buffers; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000378:metabolism; D015314:Dialysis Solutions / Q000494:pharmacology*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D007223:Infant; D007773:Lactates / Q000494:pharmacology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010530:Peritoneal Dialysis; D010537:Peritoneum / Q000378:metabolism*; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012107:Research Design; D018401:Sample Size
D001639:Bicarbonates; D001672:Biocompatible Materials; D002021:Buffers; D015314:Dialysis Solutions; D007773:Lactates; D003404:Creatinine