Kunihiro Ishioka

Background: Chronic limb‐threatening ischemia (CLTI) is a severe form of lower‐extremity artery disease characterized by distal lesions and microcirculatory impairment, limiting revascularization efficacy. Rheocarna is a direct hemoperfusion low‐density lipoprotein (LDL) adsorption device with potential rheological and anti‐inflammatory benefits. The real‐world effectiveness of Rheocarna in patients with advanced CLTI undergoing hemodialysis (HD) remains unclear. This study evaluated clinical outcomes of Rheocarna therapy in patients with CLTI undergoing HD. Methods: We retrospectively reviewed 31 patients undergoing HD (mean [±SD] age 67 ± 11 years) with CLTI treated with Rheocarna at a single center. Primary outcomes were ulcer healing at 6 months and amputation‐free survival (AFS) at 1 year, with baseline characteristics compared between healed and non‐healed groups. Results: At 6 months, the ulcer healing, major amputation, and mortality rates were 25.8%, 35.5%, and 22.6%, respectively. The 1‐year AFS rate was 40%. The mean ankle–brachial index significantly improved from 1.00 ± 0.17 to 1.07 ± 0.15 ( p = 0.041). Conclusion: Rheocarna may support wound healing and limb salvage in patients with CLTI undergoing HD; however, its clinical effectiveness appears limited in advanced disease stages.

Background: Vascular calcification (VC) is a characteristic feature of atherosclerosis in patients with chronic kidney disease (CKD), and coronary artery calcification (CAC) significantly impacts future cardiovascular events and mortality. Although factors associated with CAC are well reported, only a few studies have evaluated the factors associated with the progression of CAC in pre-dialysis patients with CKD. Methods: We quantitatively evaluated CAC progression using the CAC score (CACS) measured using 16-row multi-detector computed tomography and assessed associated factors in 74 patients with CKD. Results: The median annual increase in CACS was 23.7 (IQR 2.0–73.0). CAC progression was associated with serum phosphate and plasma asymmetric dimethylarginine (ADMA) levels, an endogenous inhibitor of nitric-oxide synthase and a marker of endothelial dysfunction and atherosclerosis, in univariate analysis. Multivariate analysis revealed that ADMA is an independent risk factor for CAC progression in patients with CKD. The annual change in CACS was significantly different between patients with ADMA values 0.51 (p < 0.05). Elevated ADMA levels were also significantly associated with estimated glomerular filtration rate (eGFR) decline in the univariate analysis. Conclusions: ADMA is a novel risk factor for CAC progression in patients with CKD. Vascular endothelial cell dysfunction, represented by elevated ADMA levels, may contribute to the progression of vascular calcification in patients with pre-dialysis CKD.

Background: Although hemodialysis (HD) patients have an elevated risk of strokes, there are few reports about transcranial doppler (TCD) echography measurements. It is well-known that angiotensin II receptor blockades (ARBs) protect against cardiovascular complications. In this study, we measured intracranial artery (ICA) velocity using TCD echography and studied the associated factors with its velocity in HD patients by a comparison with or without ARBs. Methods: We conducted a cross-sectional study in a single hospital. We included 61 patients who had measurable ICA velocity by TCD echography. Among them, the ARB usage group consisted of 22 subjects, whilst the non-ARB usage group consisted of 39 subjects. Results: Patients in the ARB (+) and ARB (-) groups did not show any difference in basic characteristics. ICA blood flow velocity in all intracranial arteries tended to show greater values in the ARB group than those in the non-ARB group. Particularly, blood velocity in the middle cerebral artery (MCA) (maximal flow velocity) statistically increased in the ARB group, respectively. In a univariate analysis, MCA maximum velocity was significantly associated with ARB usage (p = 0.011) and low hematocrit levels (p = 0.045). The multivariate analysis chose only ARB usage as an independent factor associated with left MCA maximum velocity (p = 0.022). Conclusions: We showed that dialysis patients with ARBs have significantly higher ICA blood velocity. ARBs might have a potential benefit for maintaining ICA blood flow in HD patients.

Background: The link between arterial stiffness and mild cognitive impairment (MCI) in patients on hemodialysis (HD) has been receiving increased attention. The purpose of this study was to investigate the relationship between cognitive function and ankle brachial index (ABI) and toe brachial index (TBI) values in patients on hemodialysis. Of the 100 participants (mean age: 67.9 years; average history of hemodialysis: 7.3 years). Of these, 46.0% had MCI. The MoCA-J scores were significantly higher in the ABI ≥ 1.06 group. However, the MoCA-J scores divided into the two groups according to the TBI cutoff value were not significantly different. In a multiple regression model with the MoCA-J scores as the objective variable, the ABI was a significantly associated factor. This study indicates that a low ABI might be associated with MCI.

It is unclear whether the severity of sleep-disordered breathing (SDB) affects the risk of cardiovascular events and mortality in patients undergoing hemodialysis (HD). We determined the severity of SDB with the 3% oxygen desaturation index (ODI) via overnight pulse oximetry. This study was a retrospective cohort, observational study of 134 patients on maintenance HD at a single center. They were divided into four groups according to SDB severity (normal, mild, moderate, and severe), and were followed. The baseline characteristics of all patients were as follows: the median age was 67 (interquartile range, 59–75) years, 64.2% were men, 37.3% were diabetic, and the median duration of HD was 69 (29–132) months. During follow-up, major adverse cardiovascular events (MACEs) occurred in 71 patients and deaths in 60 (including 32 cardiovascular deaths). Severe SDB was an independent risk factor for MACEs (hazard ratio [HR] = 4.66, 95% confidence interval [CI] = 1.87–11.61, p = 0.001) and all-cause death (HR = 5.74, 95% CI = 1.92–16.70, p = 0.001). Severe SDB had a statistically significant impact on the risk of MACEs and mortality in patients undergoing HD. The severity of the 3% ODI via overnight pulse oximetry may be a useful marker as a risk factor for cardiovascular outcomes and mortality in these patients.

Objectives: Zinc deficiency (Zn < 60 μg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis (HD) patients. Methods: Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn <60 μg/dL during pre-HD blood sampling. The association between zinc deficiency and aorta stiffness was analyzed. Aorta stiffness was evaluated as brachial-ankle pulse wave velocity (baPWV). Other surrogate markers for cardiovascular complications were also measured. Results: The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (p<0.05). After adjusting for hypoalbuminemia, and CRP, multivariate analysis showed that age and zinc level were independent predictors of baPWV. Conclusion: The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation.

Cardiac dysfunction is an important prognostic predictor of cardiovascular mortality in patients on hemodialysis (HD). Erythropoietin (EPO) has been reported to improve cardiac function by binding to the EPO receptor (EPOR) on cardiomyocytes. This study investigated whether anti-EPOR antibodies were associated with left ventricular cardiac function in patients undergoing HD. This multicenter, cross-sectional observational study included 377 patients (median age, 70 years; 267 (70.8%) males) with chronic kidney disease (CKD) undergoing stable maintenance HD. Serum levels of anti-EPOR antibodies were measured, and echocardiography was used to assess the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Anti-EPOR antibodies were found in 17 patients (4.5%). LVMI was greater (median of 135 g/m² vs. 115 g/m², p = 0.042), and the prevalence of LVEF < 50% was higher (35.3% vs. 15.6%, p = 0.032) in patients with anti-EPOR antibodies than in those without. Multivariable linear regression and logistic regression analysis (after adjusting for known risk factors of heart failure) revealed that anti-EPOR antibodies were independently associated with LVMI (coefficient 16.2%; 95% confidence interval (CI) 1.0–35.0%, p = 0.043) and LVEF p = 0.041). Thus, anti-EPOR antibody positivity was associated with left ventricular dysfunction in patients undergoing HD.

Objectives Zinc deficiency (Zn < 60 μg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis(HD) patients. Methods Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn Results The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (pConclusion The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation.

Pleural effusion in hospitalized patients with long-term hemodialysis (HD) has been frequently reported. The most common causes of unilateral pleural effusions include hypervolemia, parapneumonic, uremic effusion, and malignancy. In contrast, central venous stenosis (CVS) has rarely been shown to result in pleural effusion. CVS is often diagnosed by percutaneous angiography, yet there are no reports of cases where percutaneous angiography missed CVS and instead intrathoracic endoscopy was performed. Herein, we report a case of CVS with angiectasia of the parietal pleura detected on intrathoracic endoscopy. A 62-year-old man with HD presented with massive unilateral pleural effusion. Although the cause of pleural effusion was suspected to be CVS, percutaneous angiography did not show apparent stenosis, and as a result, other potential causes of bloody effusion were investigated. The intrapleural cavity was assessed using intrathoracic endoscopy, which revealed angiectasia and no malignancy. As these findings might be suggestive of congestive and dilated vessels with venous stenosis or occlusion, 3D-computed tomography (CT) scans were performed instead of percutaneous angiography to determine whether a stenosis or occlusion was present. Brachiocephalic vein stenosis was found near the aortic arch. CVS was treated through ligation of the arteriovenous fistula (AVF), resulting in a dramatic decrease in the left pleural effusion. This case would suggest that CVS should be suspected when angiectasia of the parietal pleura is observed in HD patients. In addition, the benefit of utilizing 3D-CT should be considered when HD patients present with a unilateral hemothorax on the same side as that of the AVF, particularly when on the left side.

Background: Approximately, 20–70% of patients with cholesterol crystal embolism (CCE) have eosinophilia. However, it remains unknown how eosinophilia influences renal prognosis in patients with CCE. In this study, we investigated the association between eosinophil count (Eo) and renal prognosis in CCE patients on steroid therapy. Methods: The present study is a single-centered retrospective cohort study in patients with renal dysfunction and CCE from April 2007 to May 2018. This study included the patients who were treated with neither maintenance dialysis nor steroid before CCE diagnosis, and followed-up for kidney function until November 2019. We assessed whether eosinophilia at the time of CCE diagnosis was related to renal death after treating with steroid therapy. Results: Thirty patients with pathologically diagnosed CCE were enrolled and followed-up for 11.0 (5.2–43.4) months. There were significant differences in the white blood cell count (p = 0.01), hemoglobin (p = 0.009), serum creatinine levels (p = 0.008), phosphate (p = 0.049), and Eo (p = 0.008) between the renal survival and renal death groups. Using the receiver operating characteristic curve analysis with Youden index, Eo of 810/µL showed 100% sensitivity and 69.6% specificity for detecting renal death (area under the curve: 0.839). Comparing the outcomes in patients having Eo ≥ and < 810/µL using the log-rank test, there is a significantly higher renal death rate in CCE patients with Eo ≥ 810/µL (p = 0.0016). Conclusion: Higher eosinophilia was a prognostic risk factor for renal death in the patients with CCE.