Uremic levels of oxalic acid suppress replication and migration of human endothelial cells.

Abstract

Patients with chronic renal failure who undergo hemodlalysis experience accelerated atherosclerosis and premature death. Since the end-metabolite, oxalic acid, accumulates In plasma In proportion to the severity of renal failure, we studied whether sodium oxalate (0 to 300 /tM) Is an endothellal toxin and, therefore, might enhance atherogenesls. Exposure to uremic levels of oxalate (>30 /JM) for 9 to 28 days depressed endothelial cell replication by 33% to 84% (mean±SD, 54%±15.7%, n=17 experiments, p=0.002.). In contrast, replication of flbroblasts exposed to 200 /iM oxalate for 45 days was not Inhibited. The Inhibitory effect of oxalate on endothellal cell replication was both dose-and time-dependent (both p<0.0001) and was first detected 3 to 7 days after the initial exposure to oxalate.

Plasma oxalate levels in prevalent hemodialysis patients and potential implications for ascorbic acid supplementation

“…Our data in conjunction with past observations suggest that, if calcium oxalate precipitates are formed during the interdialytic period, such precipitates may dissolve post-HD and oxalosis does not ensue, as long as the post-HD P[Ox] is b30 μM. Ox could still be a uremic toxin [32,33] that might exert deleterious effects outside the pathway of crystal deposition [34]. However, such effects may not occur until P[Ox] is sustained above 30 μM [34].…”

“…Ox could still be a uremic toxin [32,33] that might exert deleterious effects outside the pathway of crystal deposition [34]. However, such effects may not occur until P[Ox] is sustained above 30 μM [34]. Based on our data, levels in this range are now less commonly seen in HD patients, but may be more common in patients with advanced CKD not on dialysis [12].…”

Ethylene Glycol Induced Hyperoxaluria Increases Plasma and Renal Tissue Asymmetrical Dimethylarginine in Rats: A New Pathogenetic Link in Hyperoxaluria Induced Disorders

“…Calcium oxalate deposition was reported in atherosclerotic lesions of coronary arteries and alterations in endothelial cell function were documented in correlation with plasma oxalate. 21,22 Also, uremic levels of oxalate suppress human endothelial cell replication and migration. 23 When treated with crystals, cultured endothelial cells induce superoxide anion production, indicating the role of oxidative stress on endothelial dysfunction induced by hyperoxaluria.…”

The relationship between colonization of Oxalobacter formigenes serum oxalic acid and endothelial dysfunction in hemodialysis patients: From impaired colon to impaired endothelium

“…It is also possible that the relationship between the colon and the kidneys may also influence cardiovascular outcomes in the HD patient population. In this regard, Levin et al [23] investigated whether oxalic acid has toxic effects on the endothelium. These authors concluded that oxalic acid, because it is a uremic toxin, may inhibit endothelial cell function, replication, and migration.…”