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Published on: November 22, 2024
Hyperhomocysteinemia in chronic renal failure patients: relation to tissue factor and platelet aggregation
O Cetin1, S Bekpinar, Y Unlucerci
1Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Insights
Elevated total homocysteine (t-hcy) and tissue factor are common in chronic renal failure patients, even with vitamin supplementation. However, these thrombogenic factors did not correlate with platelet aggregation in dialysis patients.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Clinical Biochemistry
Background:
- Elevated plasma total homocysteine (t-hcy) is an independent risk factor for cardiovascular disease (CVD).
- Hyperhomocysteinemia contributes to cardiovascular risk via increased thrombotic potential.
- Chronic renal failure (CRF) patients exhibit elevated t-hcy due to impaired renal function.
Purpose of the Study:
- To investigate serum homocysteine, tissue factor, and platelet aggregation in CRF patients undergoing hemodialysis (HD) and peritoneal dialysis (PD).
- To compare these markers with early-stage CRF patients and healthy controls.
- To assess the role of vitamin B12 and folate levels in regulating t-hcy metabolism in CRF.
Main Methods:
- Measured serum homocysteine, ADP-induced platelet aggregation, and plasma tissue factor in HD, PD, early-stage CRF, and control groups.
- Determined serum vitamin B12 and folate levels.
- Analyzed correlations between t-hcy, creatinine, and tissue factor levels.
Main Results:
- All CRF patient groups showed significantly higher t-hcy levels than controls, despite multivitamin supplementation, with PD patients having the highest values.
- Plasma tissue factor levels were significantly elevated in all patient groups.
- t-hcy levels positively correlated with creatinine and tissue factor in early-stage CRF but not in dialysis patients.
Conclusions:
- Hyperhomocysteinemia and elevated tissue factor are prevalent in renal failure patients, irrespective of vitamin supplementation.
- The thrombogenic potential indicated by high t-hcy and tissue factor does not directly translate to increased platelet aggregation in these patients.
Background:
A moderate increase in plasma total homocysteine (t-hcy) is considered to be an independent risk factor for cardiovascular disease (CVD) in general population. One of the mechanisms by which hyperhomocysteinemia contributes to cardiovascular risk has been explained to be the increased thrombotic potential. Elevated t-hcy levels were also reported in chronic renal failure patients because the renal function is a major determinant of serum t-hcy levels.
Patients And Methods:
We measured serum hcy and ADP-induced platelet aggregation and plasma tissue factor as a major activator of the coagulation cascade in hemodialysis (HD), peritoneal dialysis (PD) and early stage chronic renal failure (early stage CRF) patients who are not receiving dialysis and compared with those of control. In addition, we also determined serum vitamin B12 and folat levels which are the important factors regulating the metabolism of t-hcy.
Results:
Hcy levels in all patient groups were significantly higher (HD: 20.42 +/- 1.91 micromol/l, PD: 35.47 +/- 6.30, early stage CRF: 24.39 +/- 3.06) than the normal levels (10.74 +/- 0.74) in spite of standard multivitamin supplementation. The highest t-hcy values were found in peritoneal dialysis patients. Vitamin B12 levels in hemodialysis/peritoneal dialysis patients and folat levels in hemodialysis/early stage CRF patients were also significantly above those of control. On the other hand, the significant elevations in plasma tissue factor concentration were found in all patient groups (HD: 331.4 +/- 31.3 pg/ml, PD: 306.0 +/- 30.0, early stage CRF: 277.2 +/- 25.5 and
Control:
69.5 +/- 13.5). t-hcy levels were positively correlated with creatinine (r: 0.791 p < 0.002) and tissue factor levels (r: 0.526 p < 0.05) in only early stage CRF group. The association between t-hcy and tissue factor persisted after these two parameters were adjusted for creatinine (r: 0.649 p < 0.05). On the other hand the same correlations were not observed in dialysis patient groups. In spite of the high tissue factor levels, ADP-induced platelet aggregations were found to be lower in all patient groups (HD: 102.6 +/- 6.7, PD: 98.6 +/- 7.6 and Early stage CRF: 84.9 +/- 7.6) than controls (154.9 +/- 13.7).
Conclusion:
These results suggest that hyperhomocysteinemia and increased tissue factor level are present in patients with renal failure, despite supplementation with vitamin B6 and B12 and folat. However, elevated levels of these thrombogenic factors are not linked with platelet aggregation.
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