Masayoshi Fukui

Increased Plasma S100A12 (EN-RAGE) Levels in Hemodialysis Patients with Atherosclerosis

Background: S100A12, also known as EN-RAGE (extracellular newly identified receptor for advanced glycation end products binding protein) is a ligand for RAGE, and has been proposed to contribute to the development of atherosclerosis. In this study, we examined the plasma S100A12 concentration in patients with ESRD and undergoing hemodialysis (HD) and evaluated the relation between S100A12 level and carotid intimal media thickness (IMT) by ultrasound. Methods: We measured plasma S100A12 concentration in 72 HD patients and 42 control subjects. IMT of the carotid artery was measured by high-resolution B-mode ultrasonography in 46 HD patients. Results: The mean plasma S100A12 level was 2.3-fold higher in HD patients than in control subjects (25.0 ± 2.32 vs. 10.7 ± 0.97 ng/ml, p < 0.001). Stepwise multiple regression analysis identified circulating white blood cell count as a positive independent determinant and total cholesterol and serum albumin levels as negative independent determinants of plasma S100A12 concentration. The maximum IMT was positively correlated with plasma S100A12 level. Stepwise multiple regression analysis also identified plasma S100A12 as a significant independent determinant of the maximum IMT. Conclusion: These findings suggest that S100A12 protein is involved in the acceleration of atherosclerosis in HD patients.

Predominant tubulointerstitial nephritis in a patient with systemic lupus nephritis.

In most cases of systemic lupus erythematosus (SLE), glomerular lesions are the main renal complication. Although tubulointerstitial lesions are often associated with severe glomerular lesions, predominant or isolated tubulointerstitial injury in the presence of minimal glomerular abnormalities with SLE, so-called predominant tubulointerstitial lupus nephritis, is rare. Only ten cases are reported in the English literature. Herein, we describe the case of a 64-year-old man with SLE who presented with acute renal deterioration attributable to acute tubulointerstitial nephritis. Renal biopsy showed diffuse infiltration of inflammatory mononuclear cells in the interstitium and tubulitis without significant glomerular lesions. Immunofluorescence study revealed positive staining for IgG, C3, and C1q along the renal tubular basement membrane (TBM). Electron microscopy also showed electron-dense deposits in the TBM. Other causes of tubulointerstitial injury, such as drug use and infection, were ruled out. Taking these findings together with the presence of antitubular basement membrane antibody, predominant tubulointerstitial lupus nephritis was diagnosed. Treatment with oral corticosteroids for 6 weeks improved renal function. Even after tapering of the corticosteroid, renal function and serological markers of SLE activity have remained stable in this patient for more than 12 months.

Comparison of the Effects of Quinapril and Losartan on Carotid Artery Intima-Media Thickness in Patients with Mild-to-Moderate Arterial Hypertension

Background: Ultrasonographic evidence of increased carotid intima-media thickness (IMT) is known to be associated with generalized atherosclerosis. Therapeutic blockade of the renin-angiotensin system (RAS) with angiotensin-converting enzyme (ACE) inhibitors reportedly reduces carotid IMT in humans. However, there has been no head-to-head comparison of the effects of ACE inhibitor and angiotensin receptor blocker (ARB), a newer type of RAS inhibitor, on carotid IMT. Methods: 57 hypertensive patients were randomly assigned to treatment with one of two antihypertensive drugs: ACE inhibitor (quinapril; n = 25, group Q) or ARB (losartan; n = 18, group L). Results: After 1 year of treatment, a similar decrease in mean blood pressure was observed in all groups. Carotid IMT was decreased significantly in group Q (10% decrease, p < 0.05) but did not change in group L. There were no significant changes in other atherosclerotic factors between these two groups. Conclusion: Our findings suggest that the antiatherosclerotic effect of quinapril is more potent than that of losartan in hypertensive patients. This effect appears unrelated to the drug’s antihypertensive action or to traditional atherosclerotic factors.

'Takotsubo' cardiomyopathy in a maintenance hemodialysis patient.

Abstract:  An 84‐year‐old woman undergoing maintenance hemodialysis presented with chest discomfort lasting several days and electrocardiographic abnormalities. She had stopped smoking 2 weeks earlier and was experiencing irritability. Upon admission, electrocardiography showed ST‐segment elevation in leads I, II, aVF, and V2‐6 and an abnormal Q wave in leads II, III, and aVF. Ultrasound cardiography showed left ventricular anteroapical akinesia and basal hyperkinesia. The chest discomfort disappeared without specific therapy. During hospital days 1–5, the ST‐segment elevation gradually improved. Giant negative T waves then developed. The left ventricular asynergy resolved by day 8. Radionuclide imaging with iodine‐123‐beta‐methyl‐p‐iodophenyl pentadecanoic acid, but not with technetium‐99 m‐sestamibi, showed an apical defect. Elective coronary angiography showed no stenosis. ‘Takotsubo’ cardiomyopathy was diagnosed. After discharge, the patient continued regular dialysis without cardiac symptoms. We concluded that endogenously activated sympathetic nerve action in hemodialysis patients, especially those under emotional or physical stress, might be a causative factor for Takotsubo cardiomyopathy.

Accumulation of visceral fat in maintenance hemodialysis patients

BackgroundIn hemodialysis (HD) patients, obesity has been recognized as a serious risk factor for mortality and morbidity for cardiovascular diseases. In addition, abnormalities of lipid profiles exist in these patients.MethodsIn patients undergoing maintenance HD, incidences of abnormality of lipid profiles and visceral obesity determined by computed tomography scans were compared. In addition, the relationship between visceral fat area (VFA) and brachial-ankle pulse wave velocity (baPWV), an index of arterial stiffness, or carotid intima-media thickness (IMT), an index of atherosis, was examined.ResultsThe incidence of high VFA (27.0%) was significantly greater than that of high body mass index (BMI) (9.7%), high low-density-lipoprotein cholesterol (LDL-C) (4.8%), and high triglyceride (12.7%). In patients with diabetes mellitus (DM), waist circumference and VFA showed a significant positive relationship with baPWV. baPWV was significantly higher in patients with high VFA and DM than in patients with low VFA without DM, those with high VFA without DM, and those with low VFA and DM. Carotid IMT was significantly greater in patients with high VFA and DM than in those with low VFA without DM and those with low VFA and DM.ConclusionsThe incidence of high VFA was much greater than that of high BMI, high LDL-C, or high triglyceride. Visceral fat accumulation may be related to both arterial stiffness and atherosis in diabetic patients on maintenance HD.

Quantitative estimation of myocardial salvage after primary percutaneous transluminal coronary angioplasty in patients with angiographic no reflow

Angiographic Thrombolysis in Myocardial Infarction (TIMI) flow grade <2 after primary percutaneous transluminal coronary angioplasty (PTCA), defined as angiographic no reflow, predicts poor left ventricular functional recovery and survival in patients with acute myocardial infarction (MI). To determine the relation between angiographic coronary flow and myocardial salvage in the acute phase of MI, serial technetium-99m tetrofosmin imaging was performed before, immediately after and 1 month after PTCA in 117 patients. Angiographic no reflow was observed in 23 patients (20%; group 1), while 94 patients did not have angiographic no reflow (group 2). Although there was no significant difference in the defect score before PTCA between the two groups (group 1, 14.4±5.7; group 2, 13.5±4.6), the defect score immediately after PTCA in group 1 was significantly higher than that in group 2 (group 1, 12.8±5.1; group 2, 8.9±4.6; P <0.0001). A significantly smaller change in the defect score after PTCA (before minus immediately after PTCA) was observed in group 1 as compared with group 2 (group 1, 1.7±2.0; group 2, 4.5±2.9; P <0.0001). Twenty patients in group 1 (87%) had impaired myocardial reperfusion (<4 change in the defect score immediately after PTCA), as compared with 36 patients (38%) in group 2; this difference was significant (χ2=17.5, P <0.0001). The sensitivity, specificity and accuracy of angiographic no reflow in estimating impaired myocardial reperfusion were 36%, 95% and 67%, respectively. Thus, angiographic no reflow is a highly specific, although not sensitive, marker of impaired myocardial reperfusion immediately after primary PTCA.

Soluble FcgammaRIIIa(Mphi) levels in plasma correlate with carotid maximum intima-media thickness (IMT) in subjects undergoing an annual medical checkup.

Macrophages play a major role in the development of vascular lesions in atherogenesis. The cells express FcγRIIIa (CD16) identical to that in NK cells, but with a cell type-specific glycosylation, and these soluble forms (sFcγRIIIa) are present in plasma. We measured sFcγRIIIaMϕ derived from macrophages in plasma from subjects undergoing an annual medical checkup. The levels of sFcγRIIIaMϕ increased with age, and correlated positively with body mass index, blood pressure, LDL cholesterol to HDL cholesterol ratio, triglycerides, hemoglobin A1c, and creatinine, but negatively with HDL-cholesterol levels. The sFcγRIIIaMϕ levels were related to the number of risk factors for atherosclerosis: such as aging, current smoking, diabetes, hypertension, hyper-LDL-cholesterolemia, hypo-HDL-cholesterolemia, and family history of atherosclerotic diseases. In addition, the sFcγRIIIaMϕ levels were correlated with carotid maximum intima-media thickness (IMT). These findings indicate the macrophages are activated during the incipient stage of atherosclerosis, and suggest sFcγRIIIaMϕ may be used as a predictive marker for atherosclerosis.

Scintigraphic prediction of left ventricular functional recovery early after primary coronary angioplasty using single-injection quantitative electrocardiographic gated SPECT.

ObjectiveThe clinical usefulness of characterizing reperfused myocardium by perfusion/thickening assessment using electrocardiographic gated single photon emission computed tomography (SPECT) has not been investigated. We evaluated whether single-injection gated SPECT with 99mTc tetrofosmin early after primary percutaneous coronary intervention (PCI) can predict left ventricular (LV) functional recovery. MethodsGated SPECT was performed 3 days after primary PCI in 45 patients with acute myocardial infarction and revascularized segments were classified into perfusion/thickening mismatched segments, matched normal and matched abnormal segments. Gated SPECT was repeated 3 months later to evaluate the changes in LV ejection fraction (ΔLVEF). ResultsAmong 332 revascularized segments, there were 83 mismatched segments, 163 matched abnormal segments and 86 matched normal segments. In all the patients, LVEF increased significantly from 3 days to 3 months after primary PCI (52±13 to 57±14%, P<0.0001). Patients were divided into two groups according to ΔLVEF: 24 patients with LV functional recovery (ΔLVEF ≥5%) and 21 patients without LV functional recovery. The number of mismatched segments in patients with LV functional recovery was significantly greater than that in patients without (2.7±1.7 vs. 0.8±1.4, P<0.0003) despite no differences in the number of matched abnormal and matched normal segments. There was a significant correlation between ΔLVEF and the number of mismatched segments (r=0.56, P<0.0001) and LVEF at 3 months after primary PCI was related to the number of matched abnormal segments (r=−0.78, P<0.0001). ConclusionSingle-injection gated SPECT early after primary PCI can predict LV functional recovery.

Assessment of Coronary Artery Disease in Hemodialysis Patients with Delayed Systolic Blood Pressure Response after Exercise Testing

Background: We evaluated usefulness of the postexercise systolic blood pressure (SBP) response for detecting coronary artery disease (CAD) in hemodialysis patients. Methods: A treadmill exercise testing was done, and the SBP response was measured in 44 hemodialysis patients (30 men, 14 women; age 41 to 81 years). The postexercise SBP response was defined as the ratio of SBP after 3 minutes of recovery to SBP at peak exercise. Results: The SBP ratio of the 25 subjects with coronary artery stenosis (1.01 ± 0.13) was significantly greater (p <0.01) than 19 subjects without coronary artery stenosis (0.83 ± 0.10). An SBP ratio greater than 0.92 identified CAD with higher sensitivity, specificity, and accuracy than did the conventional ST-segment depression criterion (76 vs. 56%, 90 vs. 53%, and 82 vs. 55%, respectively). Conclusion: Determination of the SBP ratio is a clinically useful, noninvasive method for accurately detecting CAD in hemodialysis patients.

Increment of cerebral blood flow by LDL-apheresis in dialysis patients with arteriosclerosis obliterans: a pilot study.

OBJECTIVE The prevalence of thrombotic cerebral infarction is higher in dialysis than in general patients. Changes in cerebral blood flow (CBF) during low-density lipoprotein cholesterol-apheresis (LDL-A) in dialysis patients with arteriosclerosis obliterans (ASO) were evaluated employing xenon-CT (Xe-CT) to investigate the possibility of CBF improvement. SUBJECTS AND METHODS Xe-CT was performed before LDL-A in 4 dialysis patients with ASO (3 males and 1 female). LDL-A was then performed once a week 10 times. After the completion of LDL-A treatment, Xe-CT was performed again to observe changes in CBF. RESULTS Before treatment, CBF in the 4 patients was lower than that in the general population in the same age group. After LDL-A treatment, CBF was improved. The improvement was observed in the cerebral cortex rather than the basal ganglia. The grade of improvement and improved cerebral region varied among the patients. CONCLUSION It was suggested that LDL-A may improve not only lower limb blood flow but also CBF. However, further investigation is necessary with regard to the influence of CBF improvement on the brain function and clinical application. The reported results need to be confirmed in larger studies.