Hideaki Shima

Cerebral microbleeds in predialysis patients with chronic kidney disease

BACKGROUND Gradient-echo T2*-weighted magnetic resonance imaging (T2*-weighted MRI) is highly sensitive for detecting cerebral microbleeds (CMBs). CMBs have been reported to be a risk factor for future cerebrovascular events and a marker of cerebral small vessel disease in the general population. Chronic kidney disease (CKD) is an independent risk factor for cardiovascular disease. The relationship between CKD and CMBs, which has not been clarified to date, is examined. METHODS In this cross-sectional study, T2*-weighted MRI of brain was performed with a 1.5-T MRI system in 162 CKD patients (CKD stages 1-5, excluding CKD stage 5(D)) and 24 normal subjects. RESULTS CMBs were found in 35 CKD patients (25.6%), but not in control subjects. CMBs were more prevalent in male patients, in those with higher blood pressure, advanced age and poor kidney function. There was a significant association between the prevalence of CMBs and the CKD stage, with higher prevalence of CMBs as the CKD stages advanced (P < 0.01). Estimated glomerular filtration rate was a significant factor associated with the prevalence of CMBs, independent of age, gender and hypertension. There was no significant relationship between CMBs and the presence of diabetes mellitus and dyslipidemia. CONCLUSIONS Decreased renal function is a significant risk factor for CMBs, independent of the presence of hypertension. Poor kidney function could be associated with future cerebrovascular events.

Serum n-3 and n-6 Polyunsaturated Fatty Acid Profile as an Independent Predictor of Cardiovascular Events in Hemodialysis Patients

BACKGROUND Unlike the n-6 polyunsaturated fatty acid (PUFA) arachidonic acid (AA), n-3-PUFAs such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) appear to have beneficial effects on inflammation, thrombosis, and cardiovascular disease (CVD). We examined possible alterations in serum PUFA profiles in patients on maintenance hemodialysis therapy and its association with CVD risk. STUDY DESIGN An observational study including cross-sectional and longitudinal analyses. SETTING & PARTICIPANTS Single-center study of 517 maintenance hemodialysis patients in an urban area in Japan. PREDICTORS Serum EPA, DHA, and AA concentrations and EPA:AA, DHA:AA, and (EPA+DHA):AA ratios. OUTCOMES CVD events, including ischemic heart disease, stroke, peripheral artery disease, pulmonary edema, and valve disease. RESULTS Hemodialysis patients showed lower (EPA+DHA):AA, EPA:AA, and DHA:AA ratios than 122 controls similar in age and sex. During follow-up, 190 CVD events were recorded. (EPA+DHA):AA ratio was not associated significantly with CVD in unadjusted analysis, but was associated significantly and inversely with CVD in Cox models adjusted for age and other confounding variables, with HRs in the range of 1.71-1.99 in the lowest versus highest quartile of (EPA+DHA):AA ratios. Similarly, EPA:AA and DHA:AA ratios showed inverse associations with CVD, whereas serum EPA, DHA, and AA concentrations were not predictive of CVD. LIMITATIONS No information for dietary intake, use of dietary supplements, or cell membrane PUFA content. CONCLUSIONS In hemodialysis patients, serum PUFA profile is unfavorably altered, and the low n-3-PUFA:AA ratios are independent predictors of CVD.

Decreased Kidney Function Is a Significant Factor Associated with Silent Cerebral Infarction and Periventricular Hyperintensities

Background/Aims: Silent cerebral lacunar infarction (SCI) and periventricular hyperintensities (PVH) have been reported to be markers of ischemic cerebral small-vessel disease and risk factors for future cerebrovascular events in the general population. The relationship between CKD and SCI/PVH is examined. Methods: In this cross-sectional study, brain magnetic resonance imaging was performed with a 1.5-T system in 324 predialysis CKD patients and in 60 normal subjects. Results: SCI was found in 103 CKD patients (31.8%), and PVH was found in 174 CKD patients (53.7%). SCI/PVH were more prevalent in patients with higher blood pressure, advanced age and decreased kidney function. There was a significant association between the prevalence of SCI/PVH and the CKD stage, with greater prevalence of SCI/PVH as the CKD stage advanced (p < 0.0001). PVH grade also advanced as the CKD stage advanced. The estimated glomerular filtration rate was a significant factor associated with the presence of SCI/PVH, independent of any other factors. There was a strong association between the prevalence of SCI/PVH (p < 0.0001). Conclusion: In CKD patients, decreased kidney function is a significant factor associated with SCI/PVH, both of which are significantly associated with each other. These results suggest that CKD patients with SCI/PVH are at greater risk of future cerebrovascular events.

Factors associated with silent cerebral microbleeds in hemodialysis patients.

BACKGROUND The recent development of gradient-echo T2*-weighted magnetic resonance imaging (MRI) has enabled the highly accurate detection of prior cerebral microbleeds (CMBs), which might indicate a higher risk of future intracerebral hemorrhage (ICH) and be a marker of cerebral small-vessel disease in the general population. The present study investigated the clinical factors associated with the presence of CMBs in hemodialysis (HD) patients. METHODS Cranial MRI, including T2*-weighted MRI, was performed on 179 HD patients without symptomatic cerebrovascular disease and 58 healthy control subjects, and we investigated the prevalence of CMBs and clinical factors associated with the presence of CMBs. We also investigated the relationship between CMBs and other cerebral small-vessel diseases. RESULTS The prevalence of CMBs was significantly higher in the HD patients than in the healthy subjects (45 patients (25.1%) vs. none in the healthy controls (0%), p < 0.0001). Multiple logistic regression analysis showed that independent and significant factors associated with the presence of CMBs were age, systolic blood pressure, diastolic blood pressure and pulse pressure. Moreover, the presence of CMBs correlated significantly with the presence of lacunar infarcts, periventricular hyperintensity and deep and subcortical white matter hyperintensity. CONCLUSIONS These findings indicated a high prevalence of CMBs among HD patients, and that older age and high blood pressure were strong factors associated with the presence of CMBs. Moreover, CMBs were closely associated with other cerebral small-vessel diseases.

Decreased serum adrenal androgen dehydroepiandrosterone sulfate and mortality in hemodialysis patients

BACKGROUND Endocrine and metabolic abnormalities may affect the survival of hemodialysis patients. Serum dehydroepiandrosterone sulfate (DHEA-S), an adrenal androgen with anabolic properties, is known to be lowered in ill patients and predicts poor outcome in the general population and in those with cardiac disease. The aims of this study were to examine a possible change in the DHEA-S level in dialysis patients and its association with survival in this population. METHODS This was an observational cohort study in 494 prevalent hemodialysis patients (313 men and 181 women) in urban area of Osaka, Japan. The main exposure was the baseline DHEA-S level in December 2004 and the key outcome was all-cause mortality during the subsequent 5 years. Also, DHEA-S levels were compared between the hemodialysis patients and 122 matched healthy controls. RESULTS The median (inter-quartile range) DHEA-S levels were 771 (447-1351) and 414 (280-659) ng/mL for male and female dialysis patients, respectively, and these values were significantly lower by 40-53% than the healthy control levels. Among the hemodialysis patients, DHEA-S was lower in women, those with older age, pre-existing cardiovascular disease, lower serum albumin and higher C-reactive protein. During the follow-up, we recorded 101 deaths. A low DHEA-S level was a significant predictor of all-cause mortality independent of potential confounders in male, but not in female, hemodialysis patients. CONCLUSIONS The serum DHEA-S level is decreased in hemodialysis patients and associated with mortality in men. These results support the growing observational evidence that uremia-induced endocrine alterations including decreased sex hormones may be linked to adverse clinical outcomes.

Factors associated with cerebral white matter hyperintensities in haemodialysis patients.

Aim:  Cerebral white matter hyperintensities (WMHs), comprising periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH) on magnetic resonance imaging (MRI), have been reported to be markers of ischaemic cerebral small‐vessel disease and risk factors for future stroke, cognitive impairment and dementia in the general population. However, there have been only a few reports describing WMHs in haemodialysis (HD) patients and these previous studies have been relatively small population studies with little investigation on prevalence and risk factors according to the regional subtypes of WMHs.

Quantitative Analysis of Abdominal Aortic Calcification in CKD Patients Without Dialysis Therapy by Use of the Agatston Score

Background/Aim: The aim of the present study was to quantitatively examine factors associated with aortic calcification in non-dialysis CKD patients. Methods: We quantitatively investigated aortic calcification from the renal artery to the bifurcation in 149 non-dialysis CKD patients (58±16 years; 96 males and 53 females, 48 diabetics; eGFR 40.3±29.3 ml/min), and measured Agatston scores using multi-slice computed tomography. Result: Of 149 patients, aortic calcification was present in 117. In patients with aortic calcification, age (p<0.001), C-reactive protein (p<0.001), and intact-PTH (p < 0.001) were significantly higher, estimated glomerular filtration rate (eGFR) was significantly lower (p<0.001), and diabetes was observed more often (p<0.05). In regards to the degree of aortic calcification, the Agatston scores correlated significantly and positively with age (ρ=0.438, p<0.001) and serum phosphate (ρ=0.208, p=0.024), and correlated significantly but negatively with e-GFR (ρ=-0.353, p<0.001). In multiple regression analysis, eGFR was associated significantly and independently with the log [Agatston score] (β=-0.346, p<0.01), after adjustment for several confounders including serum phosphate and the presence of diabetes. Conclusions: Hyperphospatemia, chronic inflammation, diabetes, and decreased GFR are associated significantly with the presence of aortic calcification in non-dialysis CKD patients. Decreased eGFR was associated significantly and independently with the quantitative degree of aortic calcification.

Cerebral white matter hyperintensity predicts cardiovascular events in haemodialysis patients

Cerebral white matter hyperintensities (WMHs), comprised of periventricular hyperintensity (PVH) and deep and subcortical white matter hyperintensity (DSWMH), have been presumed to be predictors for future stroke, cognitive impairment and dementia in the general population. However, no longitudinal studies have been performed to determine the clinical significance of WMHs in haemodialysis (HD) patients. In the present study, we investigated the influence of WMHs as a predictor of future cardiovascular disease in HD patients.

Silent Cerebral Microbleeds and Longitudinal Risk of Renal and Cardiovascular Events in Patients with CKD

BACKGROUND AND OBJECTIVES In the general population, the presence of cerebral microbleeds on T2*-weighted magnetic resonance imaging has been reported to be a predictor of future stroke. Patients with CKD have a high prevalence of microbleeds and are at higher risk of ESRD as well as cardiovascular disease, including stroke. Because endothelial dysfunction is the common pathophysiology among microbleeds, CKD, and cardiovascular disease, we hypothesized that the presence of microbleeds would be an important predictor of composite outcome, including both cardiovascular disease and renal events, in those with CKD. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS This was a prospective cohort study of 404 patients with CKD who underwent T2*-weighted magnetic resonance imaging for this study between January of 2008 and January of 2011. The primary outcome was composite of cardiovascular and renal outcomes. Cardiovascular outcomes included cardiovascular death, the new onset of myocardial infarction, coronary revascularization, stroke, and amputation/revascularization because of peripheral artery disease. Renal outcomes included doubling of the serum creatinine level and development of ESRD requiring dialysis or transplantation. RESULTS At baseline, microbleeds were present in 83 (20.5%) patients. During the follow-up median period of 2.3 years, 124 of the 404 patients experienced the composite outcome. The presence of microbleeds was associated with higher risk for the composite outcome in an unadjusted Cox model, and it remained significant after adjustment for age, sex, diabetes, and systolic BP (hazard ratio [HR], 2.58; 95% confidence interval [95% CI], 1.68 to 3.46 for composite outcome; hazard ratio, 2.41; 95% CI, 1.55 to 3.77 for renal outcome; hazard ratio, 3.46; 95% CI, 1.62 to 7.43 for cardiovascular disease outcome). CONCLUSIONS In patients with CKD, the presence of microbleeds is a novel and independent predictor of both renal and cardiovascular disease end points.

Successful Treatment of Hepatitis B Virus‐associated Membranous Nephropathy with Entecavir and Immunosuppressive Agents

1. Phipps LM, Chen SC, Kable K et al. Nosocomial Penumocystis jirovecii pneumonia: Lessons from a cluster in kidney transplant recipients. Transplantation 2011; 92: 1327–34. 2. Mitsides N, Green D, Middleton R et al. Dapsone-induced methemoglobinemia in renal transplant recipients: More prevalent than previously thought. Transpl. Infect. Dis. 2014; 16: 37–43. 3. Plotkin JS, Buell JF, Njoku MJ et al. Methaemoglobinaemia associated with dapsone treatment in solid organ transplant recipients: A two-case report and review. Liver Transpl. Surg. 1997; 3: 149–52. 4. Esbenshade AJ, Ho RH, Shintani A et al. Dapsone-induced methemoglobinaemia, a dose-related occurrence? Cancer 2011; 117: 3485–92. 5. Bluhm RE, Adedoyin A, McCarver DG, Branch RA. Development of dapsone toxicity in patients with inflammatory dermatoses: Activity of acetylation and hydroxylation of dapsone as risk factors. Clin. Pharmacol. Ther. 1999; 65: 598–605. SUCCESSFUL TREATMENT OF HEPATITIS B VIRUS-ASSOCIATED MEMBRANOUS NEPHROPATHY WITH ENTECAVIR AND IMMUNOSUPPRESSIVE AGENTS