Factors affecting cerebral oxygenation in hemodialysis patients: cerebral oxygenation associates with pH, hemodialysis duration, serum albumin concentration, and diabetes mellitus.

BACKGROUND: Patients undergoing hemodialysis (HD) often develop cerebral disease complications. Furthermore, cerebral regional saturation of oxygen (rSO2) was previously reported to be significantly lower in HD patients than in healthy subjects. We aimed to identify the factors affecting the cerebral rSO2 in HD patients. METHODS: Fifty-four HD patients (38 men and 16 women; mean age, 67.7 ± 1.2 years, HD duration, 6.5 ± 1.9 years) were recruited. Cerebral rSO2 was monitored at the forehead before HD using an INVOS 5100C (Covidien Japan, Tokyo, Japan). RESULTS: The rSO2 levels were significantly lower in HD patients compared with healthy controls (49.5 ± 1.7% vs. 68.9 ± 1.6%, p <0.001). Multiple regression analysis showed that cerebral rSO2 independently associated with pH (standardized coefficient: -0.35), HD duration (standardized coefficient: -0.33), and serum albumin concentration (standardized coefficient: 0.28). Furthermore, the rSO2 was significantly lower in HD patients with diabetes mellitus (DM), compared with patients without DM (46.8 ± 1.7% vs. 52.1 ± 1.8%, p <0.05). CONCLUSIONS: In HD patients, cerebral rSO2 was affected by multiple factors, including pH, HD duration, and serum albumin concentration. Furthermore, this is the first report describing significantly lower levels of rSO2 in HD patients with DM than in those without DM.

A Higher Cardiothoracic Ratio Is Associated with 2-Year Mortality after Hemodialysis Initiation.

UNLABELLED: A high cardiothoracic ratio (CTR) is indicative of a cardiac disorder. However, few reports have revealed an association between the CTR and mortality in patients starting hemodialysis (HD). METHODS: Patients with HD initiation (n = 387; mean age, 66.7 ± 12.7 years) were divided into the following three groups according to their CTR at HD initiation: CTR <50%, 50% ≤ CTR < 55%, and CTR ≥55%. Kaplan-Meier analysis was performed to compare 2-year all-cause mortality among these groups. Furthermore, we investigated the factors affecting their 2-year mortality using a Cox proportional hazard regression analysis. RESULTS: Sixty-five patients (17%) died within 2 years after HD initiation. Kaplan-Meier analysis showed that patients with CTR ≥55% had a higher mortality rate than those in the other groups. Cox proportional hazard regression analysis was performed using parameters with p values <0.1 among these three groups [sex, age, presence or absence of ischemic heart disease, hemoglobin levels, serum albumin levels, CTR, body mass index (BMI)] and confounding factors [presence or absence of diabetes mellitus, and estimated glomerular filtration rate (eGFR)]. Age, eGFR, BMI, and CTR ≥55% at HD initiation were identified as factors influencing 2-year mortality. CONCLUSION: CTR >55% is one of the most important independent factors to affect 2-year all-cause mortality. Thus, confirming the cardiac condition of patients at HD initiation with a CTR >55% may improve their survival.

Evaluation of cerebral oxygenation in patients undergoing long-term hemodialysis.

BACKGROUND/AIMS: Patients undergoing hemodialysis (HD) have higher occurrence rates of cerebral diseases, including uremic encephalopathy, cognitive impairment, dementia, and cerebrovascular disease, than the general population. During HD, ultrafiltration is performed to maintain an adequate fluid condition and is associated with subsequent blood volume (BV) reduction. We aimed to (1) monitor changes in cerebral oxygenation and BV reduction during HD, and (2) clarify the mechanism that influences cerebral oxygenation in HD patients. METHODS: Eighteen HD patients and 12 healthy controls were recruited. Regional saturation of oxygen (rSO2) was continuously monitored in the frontal cortex using INVOS 5100C before, during, and after HD, and in healthy controls. Relative change in BV (%ΔBV) was simultaneously monitored during HD using a BV monitor. RESULTS: Before HD, patients had significantly lower rSO2 values than controls (56.1 ± 1.4 vs. 70.4 ± 2.5%, p < 0.001). Although %ΔBV significantly decreased from 20 min to the end of HD (20 min: -3.3 ± 0.3%, p < 0.05; end of HD: -12.0 ± 1.0%, p < 0.01), changes in rSO2 values during HD were not significant. No relationship existed between rSO2 values and blood pressure levels, hemoglobin levels, oxygen pressure, HCO3(- ), oxygen saturation, and arterial O2 content before and after HD. Furthermore, changes in rSO2 were not correlated with changes in these parameters. CONCLUSION: rSO2 values before HD were significantly lower in HD patients than in healthy controls. rSO2 values were maintained during HD and were not influenced by BV reduction.

Acute severe liver dysfunction induced by febuxostat in a patient undergoing hemodialysis.

A 58-year-old man with chronic kidney disease (CKD) was admitted to our hospital for hemodialysis (HD) therapy. He had been administered allopurinol (100 mg/day) before hospitalization, and we replaced it with febuxostat (10 mg/day), a new xanthine oxidase inhibitor. Levels of aspartate aminotransferase, alanine transaminase (ALT), and lactate dehydrogenase were within the normal ranges in the morning before febuxostat administration, but 6 h after administration, these parameters increased markedly to approximately 10 times the levels before administration. Although we stopped administering febuxostat, his serum potassium levels increased at a rate of 1 mmol/L every 12 h, and he had to undergo HD daily to lower the serum potassium levels. The levels of liver function test parameters peaked on the fourth hospital day (ALT, 1134 IU/L; AST, 1485 IU/L; and LDH, 1869 IU/L) and recovered to normal ranges on the 13th hospital day. In this case, febuxostat appeared to have a relationship with acute liver dysfunction in the clinical course. Therefore, it would be important to check liver function test parameters frequently after febuxostat initiation and also to initiate a lower than usual dose of febuxostat, especially in patients with CKD and those who are undergoing HD.

C-reactive protein induces endothelial cell apoptosis and matrix metalloproteinase-9 production in human mononuclear cells: Implications for the destabilization of atherosclerotic plaque.

C-reactive protein (CRP) has been suggested to directly induce the inflammatory response leading to the progression of atherosclerosis. However, recent in vitro studies raised the possibility that the effects of CRP are caused by biologically active contaminants such as sodium azide and endotoxin. In this study, we tested whether azide- and endotoxin-free CRP induces endothelial cell apoptosis and production of proinflammatory mediators. In human endothelial cells, CRP significantly inhibited cell proliferation and increased endothelial cell apoptosis evaluated by terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and caspase-3 activity assay, which is reversed by a function-blocking antibody to Fc gamma RIIIB by 78%. Western blot analysis showed that CRP significantly attenuated flow-mediated activation of Akt, a key molecule for endothelial cell survival pathways. In human mononuclear cells, CRP-induced production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and matrix metalloproteinase-9 (MMP-9) in a concentration-dependent manner. This CRP-induced MMP-9 production was significantly inhibited by function-blocking antibodies to TNF-alpha, IL-1 beta, and Fc gamma RIIA. These findings suggest that CRP itself induces endothelial cell apoptosis and production of proinflammatory mediators. Because endothelial cell apoptosis and MMP-9 production are critical for the destabilization of atherosclerotic plaque, this study may provide insight into a role of CRP in the development of plaque rupture.

Src family kinases and nitric oxide production are required for hepatocyte growth factor-stimulated endothelial cell growth.

Hepatocyte growth factor (HGF) is a potent mitogen for vascular endothelial cells (EC); however, signal transduction pathways for HGF-stimulated EC growth remain unclear. In the present study we investigated the role of Src family kinases and nitric oxide (NO) in HGF-stimulated EC growth. Human umbilical vein endothelial cells (HUVEC) were stimulated with HGF and NO was measured by an NOx analyzing HPLC system. Activation of ERK1/2 and p38 MAPK was assessed by Western blot. NO production in HUVEC increased 1.8-fold by HGF. A Src family kinases inhibitor PP1 inhibited HGF-stimulated NO production by 71%. HUVEC growth increased 1.9-fold in cell number by HGF. PP1 and Nitro-L-arginine methylester (L-NAME) inhibited HGF-stimulated HUVEC growth by 51 and by 71%. ERK1/2 and p38 MAPK were phosphorylated by HGF and a MEK inhibitor PD98059 and a p38 MAPK inhibitor SB203580 inhibited HGF-stimulated HUVEC growth by 66% and by 58%; however, HGF-induced phosphorylation of ERK1/2 and p38 MAPK was not inhibited by L-NAME, indicating that NO is not an upstream activator of ERK1/2 and p38 MAPK. These findings demonstrated that Src family kinases regulate HGF-stimulated NO production in HUVEC and that HGF stimulates HUVEC growth through NO-dependent and NO-independent pathways.