PMID- 37723976
OWN - NLM
STAT- MEDLINE
DCOM- 20240110
LR  - 20240110
IS  - 1718-4304 (Electronic)
IS  - 0896-8608 (Linking)
VI  - 44
IP  - 1
DP  - 2024 Jan
TI  - Glucose-induced pseudohypoxia and advanced glycosylation end products explain 
      peritoneal damage in long-term peritoneal dialysis.
PG  - 6-15
LID - 10.1177/08968608231196033 [doi]
AB  - Long-term peritoneal dialysis is associated with the development of peritoneal 
      membrane alterations, both in morphology and function. Impaired ultrafiltration 
      (UF) is the most important functional change, and peritoneal fibrosis is the 
      major morphological alteration. Both are caused by the continuous exposure to 
      dialysis solutions that are different from plasma water with regard to the buffer 
      substance and the extremely high-glucose concentrations. Glucose has been 
      incriminated as the major cause of long-term peritoneal membrane changes, but the 
      precise mechanism has not been identified. We argue that glucose causes the 
      membrane alterations by peritoneal pseudohypoxia and by the formation of advanced 
      glycosylation end products (AGEs). After a summary of UF kinetics including the 
      role of glucose transporters (GLUT), and a discussion on morphologic alterations, 
      relationships between function and morphology and a survey of the pathogenesis of 
      UF failure (UFF), it will be argued that impaired UF is partly caused by a 
      reduction in small pore fluid transport as a consequence of AGE-related 
      vasculopathy and - more importantly - in diminished free water transport due to 
      pseudohypoxia, caused by increased peritoneal cellular expression of GLUT-1. The 
      metabolism of intracellular glucose will be reviewed. This occurs in the 
      glycolysis and in the polyol/sorbitol pathway, the latter is activated in case of 
      a large supply. In both pathways the ratio between the reduced and oxidised form 
      of nicotinamide dinucleotide (NADH/NAD(+) ratio) will increase, especially 
      because normal compensatory mechanisms may be impaired, and activate expression 
      of hypoxia-inducible factor-1 (HIF-1). The latter gene activates various 
      profibrotic factors and GLUT-1. Besides replacement of glucose as an osmotic 
      agent, medical treatment/prevention is currently limited to tamoxifen and 
      possibly Renin/angiotensis/aldosteron (RAA) inhibitors.
FAU - Krediet, Raymond T
AU  - Krediet RT
AD  - Division of Nephrology, Department of Medicine, Amsterdam UMC, University of 
      Amsterdam, The Netherlands.
FAU - Parikova, Alena
AU  - Parikova A
AD  - Department of Nephrology, Transplant Centre, Institute for Clinical and 
      Experimental Medicine, Prague, Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20230918
PL  - United States
TA  - Perit Dial Int
JT  - Peritoneal dialysis international : journal of the International Society for 
      Peritoneal Dialysis
JID - 8904033
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (Dialysis Solutions)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Humans
MH  - *Peritoneal Dialysis/adverse effects
MH  - Glucose/adverse effects/metabolism
MH  - Glycosylation
MH  - Peritoneum/metabolism
MH  - Dialysis Solutions/adverse effects/metabolism
MH  - Water/metabolism
MH  - Ultrafiltration
OTO - NOTNLM
OT  - AGE
OT  - GLUT-1
OT  - HIF-1
OT  - glucose
OT  - membrane changes
OT  - peritoneal dialysis
OT  - pseudohypoxia
OT  - ultrafiltration impairment
COIS- Declaration of conflicting interestsThe author(s) declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2023/09/19 06:42
MHDA- 2024/01/10 06:42
CRDT- 2023/09/19 02:53
PHST- 2024/01/10 06:42 [medline]
PHST- 2023/09/19 06:42 [pubmed]
PHST- 2023/09/19 02:53 [entrez]
AID - 10.1177/08968608231196033 [doi]
PST - ppublish
SO  - Perit Dial Int. 2024 Jan;44(1):6-15. doi: 10.1177/08968608231196033. Epub 2023 
      Sep 18.