Eriko Hirakata

Dialysis-Related Hypotension as a Cause of Progressive Frontal Lobe Atrophy in Chronic Hemodialysis Patients: A 3-Year Prospective Study

Background/Aim: Brain atrophy is known to develop more rapidly in hemodialysis (HD) patients than other individuals. The present study was designed to examine the role of HD-related hypotension in brain atrophy in patients on chronic HD. Methods: By using magnetic resonance imaging, whole brain atrophy was assessed by the ventricular-brain ratio (VBR; ventricular area/whole brain area). Frontal brain atrophy was assessed by the frontal atrophy index (FAI; frontal brain area/intracranial frontal space). The number of lacunae was also counted. We studied 32 HD patients without symptomatic neurological abnormalities or diabetes mellitus: male/female ratio 19/13; mean age ± SD 53 ± 10 (range 28–77) years; mean HD duration ± SD 11 ± 6 (range 1–22) years. Magnetic resonance imagings were taken in 1995 and 1998. All dialysis-related hypotension episodes during the same period were identified from the medical records and counted. Results: The VBR ranged from 8.8 to 18.7% in 1995 (12.8 ± 2.2%) and was not different in 1998 (13.1 ± 2.7%). However, the VBR increased by more than 5% in 14 patients, and their HD duration of 13 ± 6 years was significantly longer than that of 18 patients with stable VBR (p < 0.05). The FAI in 1995 was 62.2 ± 4.2% (range 55.8–71.3%) and decreased significantly to 59.7 ± 4.7% (range 50.2–70.9%) in 1998 (p < 0.05). The change in FAI correlated significantly with both the total number of dialysis-related hypotension episodes (r = 0.45, p < 0.05) and the increase in number of lacunae (r = 0.42, p < 0.05). Conclusion: Our results suggest that dialysis-related hypotension plays a role in progressive frontal lobe atrophy in HD patients.

Hemodialysis causes severe orthostatic reduction in cerebral blood flow velocity in diabetic patients

Orthostatic hypotension is a serious problem in patients with diabetes mellitus (DM) undergoing hemodialysis (HD). To evaluate cerebral circulation during orthostasis in patients with DM, we examined changes in mean blood flow velocity in the middle cerebral artery (VMCA) during 60 degrees head-up tilt for 5 minutes in patients with DM (six men, two women; age, 57 +/- 3 years [mean +/- SEM]; HD duration, 47 +/- 27 months) before and after bicarbonate HD by using transcranial Doppler sonography. The findings were compared with those in HD patients without diabetes (non-DM; 12 men, 5 women; age, 47 +/- 3 years; HD duration, 82 +/- 23 months). Mean blood pressure (MBP) in the supine position, hematocrit (Hct), plasma fibrinogen, and volume of fluid removed by HD were not significantly different between the two groups (MBP, 106 +/- 6 versus 103 +/- 4 mm Hg; Hct, 26% +/- 1% versus 28% +/- 1%; fibrinogen, 355 +/- 37 versus 357 +/- 27 mg/dL; fluid, 2.5 +/- 0.2 versus 2.3 +/- 0.2 L). Percentage of change in VMCA (% VMCA) during tilt was compared between the groups before and after HD. Before HD, MBP decreased significantly to 93 +/- 5 mm Hg during tilt only in patients with DM. The degree of MBP reduction was -13 +/- 2 mm Hg in DM and -2 +/- 2 mm Hg in non-DM patients (P < 0.01). % VMCA equally decreased during tilt; DM, -12% +/- 3%, and non-DM, -12% +/- 2%. After HD; MBP decreased by 36 +/- 7 mm Hg in patients with DM, which was significantly greater than before HD. VMCA also decreased in both groups after HD, and % VMCA in DM (-32% +/- 5%) was significantly greater than before HD (P < 0.01) and in non-DM patients (-13% +/- 2%; P < 0.01). % VMCA positively correlated with the percentage of change ratio of MBP during tilt in both groups after HD (DM, r = 0. 87, P < 0.01; non-DM, r = 0.61, P < 0.01). Our results showed a significant decrease in cerebral blood flow velocity during tilt of equal magnitude in both groups before HD despite differences in the level of hypotension, whereas reduction in cerebral blood flow velocity and decrease in MBP were more marked in DM after HD. Orthostasis could thus cause hemodynamically mediated brain damage after HD, especially in patients with DM.

The effect of azelastin hydrochloride on pruritus and leukotriene B4 in hemodialysis patients

Pruritus is a very common complication in chronic hemodialysis (HD) patients, however the exact mechanism for this affliction is still not known. Anti-histaminics usually failed to alleviate uremic pruritus. In others, an anti-allergic drug, which inhibits the release of chemical mediators, such as leukotrienes or histamine from mast cells, was reported to be effective. We evaluated the values of leukotriene B4 and interleukin 6 in HD patients with pruritus and the effect of an anti-allergic drug on these factors. Leukotriene B4, interleukin-6, C3a, C5a, the number of eosinophil and IgE at 0, 15 and 180 minutes after the start of regular HD in 11 HD patients suffering from pruritus and as well as in 11 HD patients without pruritus were examined. These HD patients in both groups showed significantly higher (p < 0.001) values of leukotriene B4 and C3a compared to healthy non-HD subjects. There was no difference in the leukotriene B4, interleukin-6, IgE, C3a and C5a levels between the patients with and without pruritus. Two mg/day of azelastin hydrochloride, an anti-allergic drug was orally given to the pruritus group for 3 weeks. In 5 of 11 patients, the pruritus symptoms disappeared, while in 4 of 11 they improved. Independent of the effect of the drug on pruritus, leukotriene B4 levels significantly decreased compared with those before the administration of this drug in the pruritus group (p < 0.01). Interleukin 6, C3a, C5a and the number of eosinophils demonstrated no significant change. In conclusion, although azelastin hydrochloride was effective in treating pruritus and also suppressed leukotriene B4 levels in hemodialysis patients, the high leukotriene B4 activity itself did not seem to be related to the development of pruritus in these patients.