Relative Contributions of Pseudohypoxia and Inflammation to Peritoneal Alterations with Long-Term Peritoneal Dialysis Patients

. 2022 Aug ; 17 (8) : 1259-1266. [epub] 20220215

Jazyk angličtina Země Spojené státy americké Médium print-electronic

Typ dokumentu časopisecké články, přehledy

Perzistentní odkaz   https://www.medvik.cz/link/pmid35168992
Odkazy

PubMed 35168992
PubMed Central PMC9435980
DOI 10.2215/cjn.15371121
PII: 01277230-202208000-00025
Knihovny.cz E-zdroje

Long-term peritoneal dialysis is associated with alterations in peritoneal function, like the development of high small solute transfer rates and impaired ultrafiltration. Also, morphologic changes can develop, the most prominent being loss of mesothelium, vasculopathy, and interstitial fibrosis. Current research suggests peritoneal inflammation as the driving force for these alterations. In this review, the available evidence for inflammation is examined and a new hypothesis is put forward consisting of high glucose-induced pseudohypoxia. Hypoxia of cells is characterized by a high (oxidized-reduced nicotinamide dinucleotide ratio) NADH-NAD+ ratio in their cytosol. Pseudohypoxia is similar but occurs when excessive amounts of glucose are metabolized, as is the case for peritoneal interstitial cells in peritoneal dialysis. The glucose-induced high NADH-NAD+ ratio upregulates the hypoxia-inducible factor-1 gene, which stimulates not only the glucose transporter-1 gene but also many profibrotic genes like TGFβ, vascular endothelial growth factor, plasminogen activator inhibitor-1, and connective tissue growth factor, all known to be involved in the development of peritoneal fibrosis. This review discusses the causes and consequences of pseudohypoxia in peritoneal dialysis and the available options for treatment and prevention. Reducing peritoneal exposure to the excessively high dialysate glucose load is the cornerstone to avoid the pseudohypoxia-induced alterations. This can partly be done by the use of icodextrin or by combinations of low molecular mass osmotic agents, all in a low dose. The addition of alanyl-glutamine to the dialysis solution needs further clinical investigation.

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