Depressed cerebral oxygen metabolism in patients with chronic renal failure: a positron emission tomography study.

To elucidate brain oxygen metabolism in uremic patients, regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and oxygen metabolism (rCMRO(2)) were measured by positron emission tomography (PET) in 10 hemodialysis (HD) patients and 13 predialysis patients with chronic renal failure (CRF). Data were compared with 20 nonuremic patients (controls) without neurological abnormalities, congestive heart failure, history of cerebrovascular accident, diabetes mellitus, or symptomatic brain lesion on magnetic resonance imaging. In the hemisphere, rCMRO(2) in both HD (1.82 +/- 0.10 mL/min/100 g) and CRF patients (1.95 +/- 0.09 mL/min/100 g) showed significantly lower values compared with controls (2.23 +/- 0.05 mL/min/100 g; P < 0.01). Hemispheric rCBF in HD (35.6 +/- 2.1 mL/100 g/min) and CRF patients (36.1 +/- 2.1 mL/100 g/min) was not different from controls (31.8 +/- 1.4 mL/100 g/min). Hemispheric rOEF in CRF patients (45.7% +/- 1.6%) was significantly greater than that in controls (40.5% +/- 1.2%; P < 0.02), but rOEF in HD patients (43.7% +/- 1.9%) did not increase significantly. These tendencies were similar in all regions of interest, especially cerebral cortices. All PET parameters in frontal cortices tended to show the lowest values in patients with renal failure. For all HD patients, rCBF in both the frontal cortex and white matter correlated inversely with HD therapy duration (P < 0.05). In conclusion, brain oxygen metabolism is depressed in patients with renal failure on or before the start of HD therapy. The cause for depressed brain oxygen metabolism is considered to be either dysregulation of cerebral circulation or lower brain cell activity.

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.

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Cerebral ischemia as a causative mechanism for rapid progression of brain atrophy in chronic hemodialysis patients.

BACKGROUND: It has been found that brain atrophy develops more rapidly in patients with end-stage renal failure after initiation of dialysis therapy. The present study was designed to analyze the relationship between brain atrophy and asymptomatic ischemic brain lesions. PATIENTS AND METHODS: Magnetic resonance imaging (MRI) was performed for the evaluation of brain atrophy and ischemic lesions. Brain atrophy was assessed by the ventricular-brain ratio (VBR), calculated as the ratio of the ventricular area to the whole brain area on the maximum MRI slice. The severity of periventricular hyperintensity (PVH) and the number of lacunae were also regarded as ischemic brain lesions. Fifty-five patients undergoing maintenance hemodialysis (HD) without clinically overt neurological signs and symptoms, with a mean age of 52 +/- 11 (SD) years and a mean HD duration of 7 +/- 6 (SD) years were subjected. VBR and its relationship to ischemic brain lesion data were compared to those in 35 non-HD patients (controls), with a mean age of 42 +/- 14 (SD) years. RESULTS: The VBR, the number of lacunae and the severity of PVH tended to increase with age in HD. The VBRs at all age groups were significantly higher in HD than in controls (7.0 vs 3.7% at the 4th decade, p < 0.05; 8.4 vs 5. 9% at the 5th decade, p < 0.05; 9.6 vs 5.4% at the 6th decade, p < 0.05; and 11.6 vs 6.3% at the 7th decade, p < 0.05). HD patients had significantly higher number of lacunae and had more advanced PVH than did controls. Both the number of lacunae and the severity of PVH were significantly correlated to VBR in HD. CONCLUSION: In conclusion, the rapid progression of brain atrophy was related to the asymptomatic ischemic brain lesions in our HD patients. Such data indicated that cerebral ischemia might be a causative mechanism of brain atrophy in chronic hemodialysis patients.