Benefits of switching from a conventional to a low-GDP bicarbonate/lactate-buffered dialysis solution in a rat model

Benefits of switching from a conventional to a low-glucose degradation product (GDP) bicarbonate/lactate-buffered dialysis solution in a rat model.BackgroundLong-term exposure to standard peritoneal dialysis fluid (PDF) results in alterations in peritoneal morphology and function. Studies investigating the long-term effects on the peritoneum of a low-glucose degradation product (GDP) bicarbonate/lactate-buffered PDF demonstrated its superior biocompatibility. We examined the potential of the low-GDP bicarbonate/lactate-buffered solution to reverse or reduce standard PDF-induced peritoneal alterations.MethodsFemale Wistar rats received twice daily intraperitoneal infusions with either a lactate-buffered solution with 3.86% glucose at pH 5.5 (Dianeal®, referred to as standard PDF), or a low-GDP bicarbonate/lactate-buffered solution with 3.86% glucose at physiologic pH (Physioneal®, referred to as bicarbonate/lactate PDF) for different periods of time: (1) 12 weeks Dianeal® (N = 9); (2) 12 weeks Physioneal® (N = 9); (3) 20 weeks Dianeal® (N = 11); (4) 20 weeks Physioneal® (N = 10); (5) 12 weeks Dianeal® followed by 8 weeks Physioneal® (N = 10).ResultsChronic standard PDF exposure resulted in loss of ultrafiltration capacity, increased VEGF expression and vascular density, higher advanced glycation end product (AGE) accumulation, up-regulation of TGF-β expression, and development of fibrosis compared to low-GDP bicarbonate/lactate-buffered PDF. The PDF-induced alterations were time-dependent. Crossover from standard PDF to low-GDP bicarbonate/lactate PDF resulted in a less impaired ultrafiltration (UF), less pronounced VEGF expression and neoangiogenesis, and less severe AGE accumulation, TGF-β expression, and fibrosis compared to continuous standard PDF exposure for 20 weeks.ConclusionLow-GDP bicarbonate/lactate-buffered PDF has the potential to slow down standard PDF-induced peritoneal membrane damage

Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane

Long-term exposure to new peritoneal dialysis solutions: Effects on the peritoneal membrane.BackgroundChronic exposure to peritoneal dialysis fluid (PDF) affects the peritoneum, but precise causative factors are incompletely understood. We examined the effects of standard and new PDF on peritoneal function and structure.MethodsFemale Wistar rats received twice daily intraperitoneal infusions of a standard lactate-buffered 3.86% glucose PDF at pH 5.5 (Dianeal®) (N = 12), a low glucose degradation product (GDP) containing bicarbonate/lactate-buffered 3.86% glucose PDF at pH 7.4 (Physioneal®) (N = 12), a lactate-buffered amino acid–based PDF at pH 6.7 (Nutrineal®) (N = 12) or Earle's Balanced Salt Solution at pH 7.4 (EBSS) (N = 12) during 12 weeks.ResultsNet ultrafiltration was lower after treatment with standard PDF, but not with low-GDP bicarbonate/lactate-buffered and amino acid–based PDF, compared to EBSS. Peritonea exposed to standard PDF were characterized by an increased expression of vascular endothelial growth factor (VEGF), microvascular proliferation as well as submesothelial fibrosis, which were not observed in other groups. Staining for methylglyoxal adducts was prominent in the standard PDF-exposed group, mild in the low GDP bicarbonate/lactate-buffered group and absent in the other groups. Standard PDF induced accmulation of advanced glycation end products (AGEs) and up-regulation of the receptor for AGE (RAGE). AGEs accmulation was absent and RAGE expression was only modestly increased in low-GDP bicarbonate/lactate-buffered and amino acid–based PDF.ConclusionLong-term in vivo exposure to standard PDF adversely affects peritoneal function and structure. A low-GDP bicarbonate/lactate-buffered and amino acid–based PDF better preserved peritoneal integrity and may thus improve the longevity of the peritoneal membrane. GDPs and associated accelerated AGE formation are the main causative factors in PDF-induced peritoneal damage

Transcortin and vitamin D-binding protein levels in mouse serum.

The influence of age, sex and strain on the serum concentration of transcortin (corticosteroid-binding globulin) and vitamin D-binding protein (DBP) in mice was investigated. The effect of age was studied in two strains, C57BL/6JPfd and BALB/cmHeAPfd. The concentration of transcortin and DBP increased with age. In young animals the concentration of each protein showed a significant strain difference, which disappeared in older mice for DBP, but not for transcortin. In 7-day-old animals, no sex difference was observed for either protein, but in older animals a clear sex difference was found for transcortin. Adult males tended to have somewhat higher levels of DBP than adult females, but this difference was significant only on day 70. The variation in transcortin and DBP levels was further investigated in a large number of mouse strains. The DBP concentration did not markedly vary among strains (5.98-9.65 mumol/l in males and 5.08-8.85 mumol/l in females). Transcortin, however, showed marked strain variations, ranging from 0.72 to 2.06 mumol/l in males and from 1.02 to 4.55 mumol/l in females and there was a significant correlation (r = 0.66, n = 26, P less than 0.001) between the mean transcortin levels in males and females of different strains. Interstrain variation was much higher than intrastrain variation or variation among related strains, suggesting that the transcortin concentration is largely controlled by genetically determined factors. There was a significant correlation (r = 0.82, n = 9, P less than 0.01) between the mean corticosterone and transcortin concentrations (measured at 21.00 h).(ABSTRACT TRUNCATED AT 250 WORDS