Incidence, outcome, and risk factors of cerebrovascular events in patients undergoing maintenance hemodialysis.

We retrospectively investigated the incidence and prognosis of and risk factors for cerebrovascular events in 1,064 patients with chronic uremia who received maintenance hemodialysis (HD) for more than 3 months during 24 years in our dialysis units in Miyazaki, Japan. Cerebrovascular events developed in 98 patients (9.2%). The confirmed incidences of cerebral hemorrhage (CH) and infarction were 8.7 and 3.7 per 1,000 patient-years, respectively. Of the 56 patients with CH, 40 (71.4%) died within 3 months of the onset of CH. Ganglio-thalamic lesion was observed in 32 (80.0%) of 40 patients with CH confirmed by a brain computed tomography. The incidence of polycystic kidney disease was higher in the CH group than in the overall HD population (12.5% v 3.9%, P < 0.01). Of the 13 patients with diabetes mellitus and nephrosclerosis, nine (69.2%) developed CH within 36 months of the initiation of HD; 11 (78.6%) of 14 patients with chronic glomerulonephritis developed CH after 36 months. CH developed in six patients (15.0%) within 6 hours of a previous HD session. We compared laboratory values, the supine blood pressure, and electrocardiographic (ECG) findings in 35 patients with CH and a control group (66 patients) matched in age, sex, basal renal disease, age at the initiation of HD, and the duration of HD. Data were obtained before and after HD 3 to 4 months before the first attack of CH. The systolic and diastolic blood pressure (SBP, DBP) before and after HD were significantly higher in the CH group than in the control group (pre-HD SBP: 171 +/- 22.5 v 154 +/- 19.3 mm Hg, P < 0.001; pre-HD DBP: 89 +/- 13.6 v 81 +/- 9.6 mm Hg, P < 0.001). The incidence of left ventricular hypertrophy was higher, and the Kt/V was significantly lower (1.23 +/- 0.26 v 1.38 +/- 0.34, P < 0.05) in the CH group than in the control group. However, there were no significant differences in the serum levels of albumin and cholesterol or the total dose of heparin during HD sessions between groups. In conclusion, the incidence of CH was high, and its prognosis was poor, in patients undergoing maintenance HD. Reversible risk factors include hypertension and possibly the amount of HD prescribed, but not anticoagulation with heparin.

A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity.

A glucokinase regulatory protein has been reported to exist in the liver, which suppresses enzyme activity in a complex with fructose 6-phosphate, whereas no corresponding protein has been found in pancreatic beta cells. To search for such a protein in pancreatic beta cells, we screened for a cDNA library of the HIT-T15 cell line with the cDNA of glucokinase from rat islet by the yeast two hybrid system. We detected a cDNA encoding the precursor of propionyl-CoA carboxylase beta subunit (pbetaPCCase), and glutathione S-transferase pull-down assay illustrated that pbetaPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts. Functional analysis indicated that pbetaPCCase decreased the K(m) value of recombinant islet glucokinase for glucose by 18% and increased V(max) value by 23%. We concluded that pbetaPCCase might be a novel activator of glucokinase in pancreatic beta cells.