cysteinylglycine and Kidney-Failure--Chronic

Thiol compounds such as glutathione, homocysteine, and cysteinyl-glycine are the natural reservoir of reductive capacity of the cells. Chronic renal failure is accompanied by disturbances in redox status of plasma thiols. The aim of the present study was to compare the changes in concentrations of different forms of thiols in plasma of terminal renal failure patients, nondialyzed and on peritoneal dialysis. Total concentrations of different redox forms of thiols were determined by high performance liquid chromatography. We observed that total concentration of glutathione in terminal renal failure patients decreased and total concentration of the remaining thiols in these patients significantly increased. Continuous ambulatory peritoneal dialysis had the following features in comparison with nondialyzed patients: (1) glutathione and cysteine concentration was restored and (2) free fraction of thiols rose, while protein-bound fraction dropped (except for homocysteine). Continuous ambulatory peritoneal dialysis corrects total concentration of glutathione and cysteine, in comparison with nondialyzed patients.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Chromatography, High Pressure Liquid; Cysteine; Dipeptides; Female; Glutathione; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Statistics, Nonparametric; Sulfhydryl Compounds

Hyperhomocysteinemia, a risk factor for cardiovascular disease, is present in the majority of patients with chronic kidney disease (CKD). Several studies indicated that the moiety of homocysteine (Hcy) with an unbound -SH group (reduced Hcy [rHcy]) is the atherogenic molecule. This study is designed to examine the relation between different forms of Hcy and other aminothiols in hemodialysis (HD) patients, peritoneal dialysis (PD) patients, and nondialyzed patients with CKD.. rHcy, free Hcy (fHcy), and total Hcy (tHcy), as well as different forms of cysteine, cysteinyl-glycine, and glutathione, were studied by using a high-performance liquid chromatography technique in 19 HD patients, 12 PD patients, 47 patients with CKD, and 15 control subjects.. In PD patients, tHcy levels were 2.8 times greater compared with controls, and in HD patients and those with CKD, 2.1 and 1.9 times greater, respectively. Mean rHcy/tHcy ratios were significantly greater in both HD (P < 0.05) and PD patients (P < 0.01), but did not differ in patients with CKD compared with controls. The decrease in rHcy levels during 1 HD treatment was smaller than that in tHcy and fHcy levels, and rHcy/tHcy ratio increased (before HD, 1.25% +/- 0.44%; after HD, 1.44% +/- 0.66%; P < 0.05).. Levels of rHcy and other aminothiols are markedly increased in patients with impaired renal function. In dialysis patients, rHcy/tHcy ratio is markedly elevated and shows greater variability than in patients with CKD and controls. We conclude that because rHcy is believed to induce endothelial dysfunction and may be part of the accelerated atherogenic process in patients with CKD, plasma rHcy level could be a more relevant marker of cardiovascular disease risk than tHcy level.

Topics: Adult; Aged; Atherosclerosis; Biomarkers; C-Reactive Protein; Chronic Disease; Cysteine; Dipeptides; Female; Folic Acid; Glutathione; Hemodiafiltration; Homocysteine; Humans; Hyperhomocysteinemia; Kidney; Kidney Diseases; Kidney Failure, Chronic; Male; Middle Aged; Oxidation-Reduction; Peritoneal Dialysis; Peritoneal Dialysis, Continuous Ambulatory; Renal Dialysis; Vitamin B 12

The metabolism of sulphur amino acids and sulph-hydryls is altered in end-stage renal disease (ESRD). Previous studies have focused on the role of vitamin status in the development of hyperhomocysteinaemia in such patients, but little information exists about the influence of global nutritional status and hypoalbuminaemia on sulphur-containing compounds in ESRD. As considerable fractions of sulph-hydryls in blood are present in erythrocytes (RBC), which among others participate in intra-organ amino acid transport, the relationship between plasma and RBC levels of several of these compounds and various nutritional parameters were evaluated in the present study.. Thirty-seven ESRD patients (24 males, 13 females) on dialysis treatment (18 haemodialysis, 19 continuous ambulatory peritoneal dialysis) and 21 healthy subjects (seven males, 14 females) were examined. The subjective global nutritional assessment (SGNA) showed that 10 (27%) patients were malnourished and 27 (73%) had normal nutritional status.. All the ESRD patients had high plasma total homocysteine (tHcy) levels. The plasma concentrations of methionine (Met) and taurine (Tau) were low, but the levels of the other sulphur-containing compounds were high. In the RBC, the patients had higher levels of tHcy and Tau than in healthy subjects, but no difference was seen in the concentrations of glutathione (GSH), cysteinylglycine (Cys-Gly), Met, and Cys. The plasma inorganic sulphate concentrations were five times higher in the patients than in healthy subjects, but the levels did not differ significantly between the malnourished patients and those with normal nutritional status. The malnourished patients had lower plasma, but not RBC, levels of tHcy, GSH, and Cys-Gly than those with normal SGNA. Plasma tHcy correlated positively with serum (s)-albumin and anthropometric parameters and negatively with SGNA. RBC and whole blood, but not plasma, GSH concentrations were correlated with haematocrit and were significantly lower in low haematocrit patients (< or = 37%, n = 19) than in those with a high haematocrit (> 37%, n = 18).. These results show that nutritional status and s-albumin influence plasma, but not RBC, concentrations of sulph-hydryls in ESRD patients. This should be considered when the relationships between cardiovascular disease and plasma tHcy or other sulphur-containing compounds are assessed. The study also shows that GSH concentrations in RBC and whole blood are related to haematocrit and not to nutritional parameters, indicating that anaemia status rather than nutritional status determines RBC and whole blood GSH levels in ESRD patients.

Topics: Adult; Cysteine; Dipeptides; Erythrocytes; Female; Glutathione; Humans; Kidney Failure, Chronic; Male; Methionine; Nutrition Disorders; Nutritional Status; Peritoneal Dialysis, Continuous Ambulatory; Reference Values; Renal Dialysis; Sulfates; Sulfhydryl Compounds; Taurine

We here describe an ion-exchange high-performance liquid chromatography technique with electrochemical detection for rapid quantification of glutathione, homocysteine, cysteinylglycine, and methionine. The analytical validation of the technique showed within-assay and between-assay coefficients of variation between 3.1 and 4.3%, and 3.7 and 8.6%, respectively. Percentages of recovery for overload and dilution tests were between 87 and 120%. Detection limits were 1 micromol/L for methionine and 0.5 micromol/L for other compounds. There was no interference with any physiological and pharmacological substances possessing a thiol function. Aminothiol concentrations determined in 100 control subjects (50 women and 50 men) showed no age- or sex-rated differences for except for homocysteine which was increased (+ 28%) in oldest subjects of both sexes. In 60 patients at risk (30 with chronic renal failure, 30 with diabetes), homocysteine concentration was significantly increased. No variation in other aminothiols was observed in diabetic subjects. Methionine was decreased and cysteinylglycine was increased in patients with chronic renal failure. The present technique-rapid, easy to use, and reliable-appears suitable for routine application in the exploration of aminothiol metabolic pathways including mechanisms of hyperhomocysteinemia.

Topics: Aging; Calibration; Chromatography, High Pressure Liquid; Diabetes Mellitus; Dipeptides; Female; Glutathione; Homocysteine; Humans; Kidney Failure, Chronic; Male; Methionine; Quality Control; Reference Values; Risk Factors; Sensitivity and Specificity

The levels of different fractions of homocysteine, cysteine and cysteinylglycine were investigated in 17 patients on chronic hemodialysis, 9 patients with reduced renal function and 4 patients with nephrotic syndrome and compared with 14 healthy subjects. Total plasma homocysteine, cysteine and cysteinylglycine were increased in the patients with reduced renal function and in those on chronic hemodialysis. The free (non-protein-bound) forms of plasma homocysteine and cysteine were significantly increased in all groups of patients. The reduced forms of plasma homocysteine and cysteine were, however, not increased in any of the patient groups; on the contrary, reduced plasma homocysteine was significantly decreased in the group of patients with reduced renal function. These findings indicate that the plasma levels of reduced forms of the thiol compounds are relatively normal and do not merely mirror the elevation of the disulfide forms. The possible relation between homocysteine and increased atherogenesis in patients with renal failure is discussed.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cysteine; Dipeptides; Female; Homocysteine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nephrotic Syndrome; Renal Dialysis; Sulfhydryl Compounds