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Plasma reduced homocysteine and other aminothiol concentrations in patients with CKD
Bodil Sjöberg1, Björn Anderstam, Mohamed Suliman
1Division of Renal Medicine, Department of Clinical Science, Intervention, and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Insights
Reduced homocysteine (rHcy) and other aminothiols are elevated in kidney disease patients. Plasma rHcy may be a better cardiovascular risk marker than total Hcy in chronic kidney disease.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Hyperhomocysteinemia is a known cardiovascular disease risk factor, prevalent in chronic kidney disease (CKD) patients.
- Reduced homocysteine (rHcy), characterized by an unbound -SH group, is identified as the primary atherogenic form of homocysteine (Hcy).
- CKD impairs renal function, affecting the metabolism and clearance of Hcy and related aminothiols.
Purpose of the Study:
- To investigate the relationship between different forms of Hcy (total Hcy [tHcy], free Hcy [fHcy], and rHcy) and other aminothiols.
- To compare Hcy and aminothiol levels in hemodialysis (HD) patients, peritoneal dialysis (PD) patients, and non-dialyzed CKD patients against control subjects.
- To assess the clinical relevance of rHcy as a marker for cardiovascular disease risk in CKD.
Main Methods:
- Employed high-performance liquid chromatography (HPLC) to quantify rHcy, fHcy, tHcy, cysteine, cysteinyl-glycine, and glutathione.
- Studied 19 HD patients, 12 PD patients, 47 non-dialyzed CKD patients, and 15 healthy control subjects.
- Analyzed rHcy/tHcy ratios and changes in these levels during hemodialysis treatment.
Main Results:
- PD and HD patients exhibited significantly higher tHcy levels (2.8 and 2.1 times, respectively) compared to controls.
- Mean rHcy/tHcy ratios were significantly elevated in both HD and PD patients, indicating a higher proportion of the reduced, potentially atherogenic form.
- A decrease in rHcy during HD was less pronounced than for tHcy and fHcy, leading to an increased rHcy/tHcy ratio post-treatment.
Conclusions:
- Plasma levels of rHcy and other aminothiols are substantially increased in individuals with impaired renal function.
- Dialysis patients show a markedly elevated and more variable rHcy/tHcy ratio compared to non-dialyzed CKD patients and controls.
- Plasma rHcy is proposed as a more pertinent biomarker for cardiovascular disease risk in CKD patients due to its association with endothelial dysfunction and atherogenesis.
Background:
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.
Methods:
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.
Results:
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).
Conclusion:
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.
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