carboxyethyl-hydroxychroman and Kidney-Failure--Chronic

Carboxyethyl-hydroxychromans (CEHC) are hydrosoluble vitamin E metabolites excreted through the renal filter. In this study we investigated the effect of the kidney damage on the blood levels of CEHC.. Plasma levels of alpha-CEHC, gamma-CEHC and their precursors (namely, alpha-tocopherol and gamma-tocopherol) were measured by HPLC with electrochemical detection in chronic (CRF) and end-stage renal failure patients on regular hemodialysis (HD) before and after dialysis. CRF patients (n = 26) were divided into three subgroups with different extent of kidney damage as measured by the intervals of creatinine clearance (CrCl, in ml/min): (a) 2-10, (b) 10-20, and (c) 20-45. HD patients (n = 8) did not show residual renal function. In all the subjects the intake of vitamin E (as alpha-tocopherol) was assessed using a food frequency questionnaire. In the HD group, the plasma concentrations of ascorbic and uric acid (AA and UA, respectively), total thiols, the total antioxidant status (TAS) and reactive carbonyls were also measured.. The progressive deterioration of the kidney function in the different groups of patients produced an exponential increase of both alpha-CEHC and gamma-CEHC in plasma. Compared with healthy controls (alpha-CEHC = 20.1+/-13.4 and gamma-CEHC = 230.6+/-83.0 nmol/l) the levels of CEHC approximately doubled in patients with CrCl < or = 20ml/min (42.4+/-20.2 and 424.5.5+/-174.4; P <0.05 or higher in both) and reached a 3-fold maximum increase in HD patients (77.3+/-45.7 and 636.6+/-219.3). The hemodialysis provided a significant, but only a transient, correction of CEHC accumulation (44.8+/-23.5, 364.2+/-189.9). The HD patients showed lower intake and levels of vitamin E (alpha-tocopherol = 5.1+/-1.0 and gamma-tocopherol =0.32+/-0.11 micromol/mmol cholesterol; P <0.05) compared to healthy controls (5.8+/-0.8 and 0.43+/-0.14), but in the CRF patients tocopherol levels were normal or only slightly decreased even though approximately half of the subject had lowered vitamin E intake. When the entire patient population was considered, the blood concentrations of parental tocopherols and CEHC did not correlate. The HD patients before dialysis showed a marked decrease of TAS/UA, AA and thiols levels, while UA and free carbonyls significantly increased. After dialysis, the depletion of AA and thiols further worsened and also UA and TAS/UA decreased, but free carbonyls slightly increased.. The results other than to confirm the key importance of the renal route for the excretion of CEHC, demonstrate that CEHC cannot be reliably used to investigate vitamin E biokinetics and transformation without a careful examination of the renal function. CEHC accumulation does not seem to influence the antioxidant status in the plasma of HD patients. Further studies are requested to establish whether such an increase in blood CEHC concentrations might be harmful or could contribute to the biological functions of the vitamin E in uremia and dialysis patients.

Topics: Acute Kidney Injury; Adult; Aged; alpha-Tocopherol; Antioxidants; Chromans; Chromatography, High Pressure Liquid; Female; gamma-Tocopherol; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Reference Values; Renal Dialysis; Vitamin E

Vitamin E therapy (based either on oral supplements or new dialysis methods such as vitamin E-coated hemodialysers) has been suggested to yield a better clinical outcome in hemodialysis (HD) patients than in other populations of patients. Among other factors, the presence of a modified vitamin E status might help to explain this apparently paradoxical response to vitamin E. In this study we investigated 104 regular HD patients. The results indicate that, besides having a low dietary intake, these subjects show some abnormalities in the levels and metabolism of vitamin E, such as a disproportion between plasma tocopherols and lipids, low levels of gamma-T, and CEHC accumulation. Although further studies are needed to confirm the clinical relevance of vitamin E therapy in HD, these findings might lead to recommending a higher vitamin E intake in these patients.

Topics: Aged; Chromans; Diet; Female; Humans; Kidney Failure, Chronic; Lipids; Male; Middle Aged; Renal Dialysis; Vitamin E

The metabolism of alpha and gamma tocopherol, the major components of vitamin E, have not been studied in uremic patients. The major pathway of tocopherol metabolism is via phytyl side chain oxidation, leaving carboxyethyl-hydroxychromans (CEHC) as metabolites. Alpha and gamma CEHC are water soluble, renally excreted, with known potent anti-inflammatory and antioxidative properties.. We examined serum alpha and gamma tocopherol and respective CEHC concentrations in 15 healthy subjects and 15 chronic hemodialysis patients.. Serum alpha tocopherol levels were similar in hemodialysis patients (12.03 +/- 1.34 microg/mL) and healthy subjects (11.21 +/- 0.20 microg/mL), while serum gamma tocopherol levels were significantly greater in hemodialysis patients (3.17 +/- 0.37 microg/mL) compared to healthy subjects (1.08 +/- 0.06 microg/mL, P < 0.0001). Serum alpha and gamma CEHC levels were tenfold and sixfold higher in hemodialysis patients compared to healthy subjects, respectively (both P < 0.0001). Serum alpha and gamma tocopherol levels and CEHC metabolites were also measured after supplementation of alpha- or gamma-enriched mixed tocopherols in both hemodialysis patients and healthy subjects. Tocopherol administration resulted in modest or nonsignificant changes in serum tocopherol concentrations, while markedly increasing serum CEHC concentrations in both healthy subjects and hemodialysis patients. Hemodialysis resulted in no change in the serum alpha or gamma tocopherol concentrations while decreasing serum alpha CEHC and gamma CEHC levels by 63% and 53%, respectively (both P = 0.001 versus predialysis). Fourteen-day administration of gamma-enriched but not alpha tocopherols lowered median C-reactive protein (CRP) significantly in hemodialysis patients (4.4 to 2.1 mg/L, P < 0.02).. First, serum alpha and gamma CEHC accumulate in uremic patients compared to healthy subjects; second, supplementation with tocopherols dramatically increases serum CEHC levels in both healthy subjects and hemodialysis patients; and, finally, CEHC accumulation may mediate anti-inflammatory and antioxidative effects of tocopherols in hemodialysis patients.

Topics: Acute-Phase Reaction; alpha-Tocopherol; C-Reactive Protein; Case-Control Studies; Chromans; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; gamma-Tocopherol; Humans; Interleukin-6; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis