Effects of vitamin supplementation on microcirculatory disturbance in hemodialysis patients without peripheral arterial disease.

AIMS: Dysfunctional endothelium caused by oxidative stress is thought to play a role in pathogenesis of a variety of conditions including atherosclerosis. We investigated whether a microcirculatory disturbance in hemodialysis (HD) patients was associated with increased oxidative stress and endothelial injury. PATIENTS AND METHODS: Transcutaneous oxygen tension (TcPO2) on the dorsum of the foot at rest was measured as a marker of microcirculation in 33 patients undergoing HD without clinical manifestations of peripheral arterial disease and 20 healthy controls. Furthermore, in order to examine whether TcPO2 was affected by antioxidants, oral supplementation with a combination of vitamin C (200 mg daily) and vitamin E (600 mg daily) was administered for 6 months to 8 patients with microcirculatory disturbance (TcPO2 values of 50 mmHg or less). Serum biochemical parameters including vitamins were also measured. RESULTS: Mean TcPO2 value was significantly lower in HD patients than in control subjects (47.9 +/- 13.5 mmHg versus 62.4 +/- 11.9 mmHg, p < 0.001). After vitamin supplementation, TcPO2 values remarkably increased (40.6 +/- 10.0 mmHg versus 57.4 +/- 6.5 mmHg, p < 0.005). Serum vitamin C and vitamin E levels increased significantly as well, while serum levels of thrombomodulin, a marker of endothelial injury, and thiobarbituric acid reactants, a marker of lipid peroxidation, were significantly decreased in comparison with those before supplementation. CONCLUSIONS: Our results suggest that the microcirculatory disturbance in HD patients seems to be associated with endothelial damage caused by oxidative stress. Combined supplementation with vitamin C and vitamin E may be of clinical benefit in improving the cutaneous microcirculation by reducing oxidative stress.

Effects of L-carnitine supplementation on renal anemia in poor responders to erythropoietin.

While renal anemia can be successfully treated by use of erythropoietin (EPO) in most hemodialysis (HD) patients, some patients have anemia that is refractory to treatment with a high dose of EPO. We examined whether L-carnitine treatment could raise hematocrit (Hct) levels in such patients. Fourteen HD patients who showed a poor response to EPO and no evident factors which inhibit a response to EPO were selected to receive oral L-carnitine (500 mg/day) in a 3-month trial. During the study, 36% of the patients showed Hct increases of more than 2%. Statistical analysis revealed significant increases of Hct (p = 0.003) and total iron-binding capacity (TIBC) (p = 0.050) and a significant decrease of ferritin (p = 0.005). In addition, we found that red blood cells (RBCs) in HD patients contained a comparable level of carnitine to normal controls, despite the presence of serum carnitine deficiency, and that RBC carnitine was not removed through HD, in contrast to serum carnitine. These results suggest that RBC carnitine may be essential for RBCs to perform their metabolic function in renal anemia and that oral L-carnitine treatment could improve anemia in poor responders to EPO.

Effects of L-carnitine supplementation on cardiac morbidity in hemodialyzed patients.

Cardiac diseases are well known among patients on maintenance hemodialysis (HD), and carnitine deficiency may be an important factor in cardiac morbidity. We studied the effects of low-dose L-carnitine treatment (500 mg/day) on chest symptoms (dyspnea on exertion, chest pain, palpitation), cardiac function, and left ventricular (LV) mass in 9 HD patients with reduced ejection fraction (EF). After 6 months of L-carnitine treatment, most patients had at least some improvement in chest symptoms, while LVEF was increased and LV mass was decreased. Carnitine fractions increased and reached plateaus at 2-3 times the baseline levels. These results suggest that prolonged low-dose L-carnitine treatment can improve the cardiac morbidity by restoring decreased carnitine tissue levels and impaired oxidation of FFA.

Effects of L-carnitine supplementation on muscular symptoms in hemodialyzed patients.

Various muscle symptoms are well recognized among patients on maintenance hemodialysis. Carnitine deficiency may be an important factor of dialysis-associated muscle symptoms, whereas high-dose L-carnitine supplementation may result in unphysiologically high plasma levels of carnitine and carnitine esters. We studied the effect of low-dose L-carnitine treatment (500 mg/d) on muscle symptoms, plasma carnitine fractions, and lipid profiles in 30 periodically dialyzed patients with muscular weakness, fatigue, or cramps/aches. After 12 weeks of L-carnitine treatment, about two-thirds of patients had at least some improvement in muscular symptoms, whereas carnitine fractions were normal or slightly above normal ranges, but lipid profiles showed no demonstrable changes. This study also showed the correlation between plasma-free carnitine deficiency and months on dialysis. These results suggest that prolonged low-dose L-carnitine treatment can improve dialysis-associated muscle symptoms by restoring carnitine tissue levels and washing out acyl moieties.

Clinical experience with alumina ceramic transcutaneous connector to prevent skin-exit infection around CAPD catheter.

To prevent skin-exit infection, an important CAPD complication, we developed a transcutaneous connector made of Alumina ceramic. The new connector could be downsized, because an Alumina ceramic is characteristically bio-inert, rigid and non-porous. Our animal experiments with Alumina ceramic in soft tissue demonstrated the outstanding bio-compatibility of this material. The shape of the new transcutaneous connector was of simple cylindrical configuration so as to inhibit macrostress beneath the skin. To make contact with this connector in the body, a silicon tube was made into a Swan-necked catheter with a disk-shaped polyester cuff, which was positioned subcutaneously beneath the transcutaneous connector in order to reinforce adhesion to soft tissue. The silicon tube itself was L-shaped in its outside portion just before reaching the connector. We are now using this new transcutaneous connector made of Alumina ceramic on a CAPD catheter in 8 patients. In the longest case of a patient using it, there has been no skin-exit infection for 12 months. Also, there has been virtually no downgrowth phenomenon in the skin around the connector, and the connector and tissue have remained in very close contact, although fibrous connective tissue has been seen to form in the area.