Accumulation of vitamin E metabolites in the blood of renal failure patients

Background & aims: Carboxyethyl-hydroxychromans (CEHC) are hydro-soluble 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. Methods: 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. Results: 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 less than or equal to20ml/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 tower intake and levels of vitamin E (alpha-tocopherol=5.1+/-1.0 and gamma-tocopherol = 0.32+/-0.11 mumol/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. Conclusions: 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. (C) 2003 Elsevier Ltd. All rights reserved.