Achilleas Tourkantonis

Functional capacity of end-stage renal disease patients is dramatically impaired. Although exercise training programs appear to have beneficial morphological, functional and psychosocial effects in end-stage renal disease patients on hemodialysis (HD), the adherence rate is high. The purpose of this study was to compare the effects of three modes of exercise training on aerobic capacity and to identify the most favourable, efficient and preferable to patients on HD with regard to functional improvements and participation rate in the programs. Fifty-eight volunteer patients were screened for low-risk status and selected from the dialysis population. The 48 patients who completed the study protocol were randomly assigned either to one of the three training groups or to a control group. Sixteen of them (Group A - mean age 46.4+/-13.9 years) completed a 6-month supervised outpatient exercise renal rehabilitation program consisting of three weekly sessions of aerobic and strengthening training on the non-dialysis days; 10 (Group B - mean age 48.3+/-12.1 years) completed a 6-month exercise program during HD; 10 (Group C - mean age 51.4+/-12.5 years) followed an unsupervised moderate exercise program at home, and 12 patients (Group D-mean age 50.2+/-7.9 years) were used as patient controls. The level of anemia, the medications and the HD prescription remained stable during the study. Fifteen sex- and age-matched sedentary individuals (Group E - mean age 46.9+/-6.4 years) comprised a healthy control group for baseline data. All subjects at the beginning and end of the study underwent clinical examination, laboratory tests and a treadmill exercise test to fatigue endpoints with direct measurement of aerobic capacity. Group A had a higher dropout rate (24%) compared to groups B (17%) and C (17%). Peak oxygen consumption (VO2 peak) increased by 43% (p < 0.05), anaerobic threshold (VO2AT) by 37% (p < 0.05) and exercise time by 33% (p < 0.05) after training in Group A; by 24% (p < 0.05), 18% (p < 0.05) and 22% (p < 0.05), respectively, in B; and by 17% (p < 0.05), 8% (p < 0.05) and 14% (p < 0.05), respectively, in C; while both remained almost unchanged in Group D. These results demonstrate that intense exercise training on non-dialysis days is the most effective way of training, whereas exercise during HD is also effective and preferable.

BACKGROUND: Functional limitations, altered cardiac autonomic activity, and psychological distress are known disorders in chronic hemodialysis (HD) patients, relating to increased morbidity and mortality. The aim of this study was to examine the influence of an exercise training program on emotional parameters and heart rate variability (HRV) indices, as well as to determine whether emotional stress contributes to autonomic dysfunction in these patients. METHODS: Forty-four HD patients were randomly assigned into group A (24 patients, aged 46.3+/-11.2 years), who participated in a 1-year intradialytic exercise training program and group B (20 patients, aged 45.8+/-10.8 years), who were used as controls. At baseline and a year after, measures of HRV were obtained for the estimation of standard deviation of RR intervals, the mean square successive differences, percentage of RR intervals differing by more than 50 ms from the preceding RR interval (pNN50), and low to high frequency components. Emotional parameters (Beck Depression Inventory - BDI and Hospital Anxiety and Depression Scale - HADS) were also assessed by validated questionnaires. Moreover, all patients performed a spiroergometric study for the estimation of VO2peak. RESULTS: At baseline, all measurements were similar in the two groups and remained almost unchanged after a year in group B. After a year of training, VO2peak increased from 16.79+/-5.24 to 22.33+/-4.90 ml/kg per min (P<0.001) in group A. Trained patients also showed an increase in standard deviation of RR intervals by 58.8% (P<0.001), the mean square successive differences by 68.1% (P<0.001), pNN50 by 23.5% (P<0.001), and a low to high frequency ratio by 17.3% (P<0.001). Finally, at the end of the study, group A showed a decrease in BDI score by 34.5% (P<0.001) and HADS by 23.9% (P<0.001). Canonical correlation revealed significant inverse correlation among depression (in BDI and HADS) and HRV indices before and after exercise training. CONCLUSION: Cardiac autonomic modulation seemed to be sensitive to the experience of persistent depression in HD patients. Significantly, exercise training reduced emotional distress and concomitantly improved HRV.

Pruritus is a common, unpleasant symptom of uremic patients. Serotonin and histamine have been reported as possible mediators ofuremic pruritus, and ondansetron is a potent and selective inhibitor of 5-HT3 receptors. The aims of our study were (1) to evaluate the effect of ondansetron on uremic pruritus in continuous ambulatory peritoneal dialysis (CAPD) patients and its safety and (2) to investigate the role of histamine and serotonin in uremic pruritus. To study the prevalence and pathogenesis of uremic pruritus, CAPD and hemodialysis (HD) patients were asked to complete a pruritus questionnaire. The replies were scored based on numerical scales, and the results were evaluated by the same investigator who did not know the patients. Pruritus was graded, according to the total points for each patient, as mild, moderate, or severe. Of 54 patients on HD, 29 (53.7%) had pruritus, and of 43 patients on CAPD, pruritus was present in 21 (48.8%). In HD patients, pruritus was mild in 14 (48.3%), moderate in 12 (41.4%), and severe in 3 (10.3%) patients; the distribution in CAPD patients was 9 (42.9%), 10 (47.6%), and 2 (9.5%), respectively. There was no correlation between the presence and severity of pruritus and age, sex, primary renal disease, duration of dialysis, dialysis solutions used, and hematological and biochemical parameters except for serum histamine and serotonin levels and their product. Plasma histamine levels in CAPD patients were 13.1 +/- 1.1 ng/ml in pruritic and 11.0 +/- 3.9 ng/ml in nonpruritic patients (p = 0.06), serum serotonin levels were 115.6 +/- 43.3 ng/ml and 64 +/- 42.3 ng/ml (p < 0.05), respectively, and the histamine x serotonin product was 1,461 +/- 576 and 646 +/- 545 (p < 0.01), respectively. Eleven CAPD patients (6 males, 5 females) with a mean age of 66 (range 33-83) years and an average time on CAPD of 18 (range 3-31) months with moderate to severe pruritus were treated with ondansetron (4 mg twice daily p.o.) for a mean period of 3 (range 1-5) months. All patients responded to the treatment. There was a significant reduction of the severity of pruritus from the start of treatment, and on the 3rd day the pruritic score (mean value) was 10 (range 5-19) points, while at time 0 (before treatment) it was 26 (range 19-37) points (p < 0.0001). Pruritus disappeared in 7 patients at the end of the 1st week and in all patients at the end of the 2nd week of treatment. This effect was maintained during the study. Plasma histamine levels decreased significantly during the treatment from 12.9 +/- 1.2 to 6.7 +/- 5.9 ng/ml (p < 0.05). Also, serum serotonin levels were reduced from 125.1 +/- 47.8 to 59.3 +/- 27.5 ng/ml (p < 0.05) at the end of the 1st month of treatment, and the histamine x serotonin product showed a more significant reduction: from 1,544 +/- 656 to 454 +/- 436 (p < 0.01). Three patients reported an improvement in their nausea and vomiting during the treatment. Weekly clinical and laboratory examinations showed no side effects, adverse reactions, or other complications. Our data indicate that ondansetron is an effective, safe, and well-tolerated drug for the treatment of uremic pruritus in CAPD patients and that histamine and serotonin may have a crucial role in the appearance or perception of the uremic pruritus.