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Chronic Renal Failure
In uraemic condition there is defective antioxidant production and increased susceptibility to plasma lipid oxidation, oxidative damage to proteins and nucleic acids, and accumulation of molecules with pro-oxidant function such as homocysteine and some reactive carbonyls deriving from the non-enzymatic oxidation of glucose and lipids. The accumulation of reactive carbonyl compounds (RCOs) derived from carbohydrates and lipids and the subsequent carbonyl modifications of proteins "carbonyl stress". Uraemia is characterised by the simultaneous accumulation of irreversible nonenzymatic protein modifications with carbohydrates and lipids, i.e. AGEs/ALEs. Oxidative stress presents in the CRF patient in combination with a chronic antioxidant deficiency. Proteins are elective targets of oxidant-mediated injury, which lead to functional alterations and progressive loss to their metabolic, enzymatic, or immunologic properties. Intense oxidation generates insoluble products that resist proteolysis. Lysine, arginine, proline, and histidine are prone to generate carbonyls. Advanced oxidation protein products (AOPP) are of 2 types high molecular weight (HMW-AOPP) and low molecular weight (LMW-AOPP). Homocysteine, similar to cysteine, but with an additional methylene group in its side chain, is a sulfur amino acid not normally inserted into the protein backbone, which is positioned at a crucial branch point of the metabolism of the essential amino acid methionine. Homocystinuria is inherited connective tissue disease characterised by elevated blood levels of homocysteine and homocysteine, the oxidised product, in the urine. Vitamin C and vitamin E prevent alterations in endothelial cell function caused by acute hypercysteinaemia. ESRD is associated with elevated Asymmetric dimethylarginine (ADMA) levels (6-fold) and reduced levels of nitrosothiols in plasma. L-arginine restores endothelial function independently in haemodialysis. L-arginine restores endothelial function independently in haemodialysis. Haemodialysis weakens the antioxidant defences by: 1- leakage and consumption of hydrosoluble antioxidants (vitamin C, free thiol) during dialysis; 2- consumption of liposoluble/lipoprotein-associated antioxidants (vitamin E, CoQ10); 3- changes in the lipid consumption of biological fluids and cell membranes; and 4- a deficit in cofactors and damage to antioxidant enzymes such as extracellular glutathione peroxidase and HDL-associated paraoxonase. Vitamin E modulates ROS productions of neutrophils exposed to dialysis membranes. Vitamin E-modified dialyzers can lead to overall beneficial effects against oxidative stress. Modified dialyzer with vitamin E provides more effective antioxidant defense than peroral administration of vitamin E.
Find more in Urotext, E. Book simplifying Urology. Clinical Orthomolecularism Classroom
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R.A.S HEMAT, MB;BCh, FRCSI, DUL.