Showing papers by "Masaaki Nakayama published in 2010"
TL;DR: In this article, a meta-analysis of general population cohorts was conducted to assess the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality.
3,087 citations
TL;DR: A number of uremic compounds are identified, many of which are novel and which predict worsening renal function, which provide diagnostic information and may be targets for therapies designed to treat the complications of CKD patients.
Abstract: Early detection and accurate monitoring of patients with chronic kidney disease (CKD) is likely to improve care and decrease the risk of cardiovascular and cerebrovascular diseases. As a new diagnostic tool, we examined the retention of uremic solutes as a simpler, more accurate method to assess renal function. To achieve this, we comprehensively evaluated these solutes in CKD patients. By capillary electrophoresis with mass spectrometry, we found 22 cations and 30 anions that accumulated significantly as the estimated glomerular filtration rate (eGFR) decreased. These compounds included 9 cations and 27 anions that were newly identified in this study. In contrast, we also found 7 cations (2 new) and 5 anions (all new) that decrease significantly as eGFR declines. We evaluated each substance for its suitability to detect early CKD stage. Compounds that are highly correlated with eGFR and whose plasma concentration changed in a manner approximated by the first-degree equation are excellent candidates for detecting CKD and identifying uremic toxins that might aggravate kidney function in the early stage of CKD. These results identify a number of uremic compounds, many of which are novel and which predict worsening renal function. These compounds provide diagnostic information and may be targets for therapies designed to treat the complications of CKD patients.
123 citations
TL;DR: In this paper, the authors measured in 50 type 2 diabetic patients plasma levels of MG and 3-deoxyglucosone (DG) using an electrospray ionization-liquid chromatography-mass spectrometry.
Abstract: We test whether plasma level of methylglyoxal (MG) is an independent risk factor predicting the progression of diabetic macroangiopathy or microangiopathy in type 2 diabetic patients. We measured in 50 type 2 diabetic patients plasma levels of MG and 3-deoxyglucosone (DG) using an electrospray ionization-liquid chromatography-mass spectrometry. We assessed the correlations between baseline levels of MG or DG and the percentage changes after 5 years of clinical parameters linked to diabetic macroangiopathy or microangiopathy, that is, intima-media thickness (IMT), systolic blood pressure (SBP), the amount of urinary albumin excretion (ACR), pulse wave velocity (PWV), and estimated glomerular filtration rate (eGFR). Multiple regression analysis was performed using the percentage changes in IMT, SBP, ACR, PWV, and eGFR over the 5-year period as the independent or objective variables and the values of MG, DG, glycohemoglobin A1c, body mass index, triglyceride, and diabetic duration at the baseline as the dependent variables. The values of IMT, PWV, SBP, and ACR all increase, but eGFR reduces with time during the 5-year period. Baseline level of MG correlates significantly with the percentage changes of IMT, SBP, ACR, PWV, and eGFR, whereas that of DG does only with ACR. A multiple regression analysis reveals that MG is an independent risk factor for the percentage changes of IMT, PWV, and SBP but not for those of ACR and eGFR. DG is an independent risk factor for the percentage change of ACR. MG is a predictor in type 2 diabetic patients of intima-media thickening, of increase of PWV, and of elevation of SBP.
90 citations
TL;DR: Adding H(2) to haemodialysis solutions ameliorated inflammatory reactions and improved BP control and could offer a novel therapeutic option for control of uraemia.
Abstract: Background. Chronic inflammation in haemodialysis (HD) patients indicates a poor prognosis. However, therapeutic approaches are limited. Hydrogen gas (H2) ameliorates oxidative and inflammatory injuries to organs in animal models. We developed an HD system using a dialysis solution with high levels of dissolved H2 and examined the clinical effects. Methods. Dialysis solution with H2 (average of 48 ppb) was produced by mixing dialysate concentrates and reverse osmosis water containing dissolved H2 generated by a water electrolysis technique. Subjects comprised 21 stable patients on standard HD who were switched to the test HD for 6 months at three sessions a week. Results. During the study period, no adverse clinical signs or symptoms were observed. A significant decrease in systolic blood pressure (SBP) before and after dialysis was observed during the study, and a significant number of patients achieved SBP <140 mmHg after HD (baseline, 21%; 6 months, 62%; P < 0.05). Changes in dialysis parameters were minimal, while significant decreases in levels of plasma monocyte chemoattractant protein 1 (P <0 .01) and myeloperoxidase (P < 0.05) were identified. Conclusions. Adding H2 to haemodialysis solutions ameliorated inflammatory reactions and improved BP control. This system could offer a novel therapeutic option for control of uraemia.
82 citations
TL;DR: The data suggest that MGO stimulates superoxide production from mitochondria and partially stimulates nitric oxide synthase in human endothelial cells.
Abstract: Methylglyoxal (MGO) is a non-enzymatic metabolite in the glycolytic pathway and its concentration in blood and tissues is elevated in diabetes and renal failure. MGO induces tissue injuries via ROS; however, the mechanism remains to be clarified. The present study examined the harmful actions of MGO. Human aortic endothelial cells were assessed under real-time fluorescent microscopy with continuous superfusion. Increases in intracellular ROS were measured with fluorescent indicator, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate acetyl ester (DCFH-DA). The addition of MGO rapidly increased the ROS in a dose-dependent manner. The increment of DCF was entirely abolished by pre-treatment with superoxide anion scavenger and membrane-permeable catalase, indicating that MGO induces superoxide production. The increment was completely inhibited by 2-thenoyltrifluoroacetone or carbonyl cyanide 3-chlorophenylhydrazone and partially inhibited by N-methyl-L-arginine. These data suggest that MGO stimulates superoxide production from mitochondria and partially stimulates nitric oxide synthase in human endothelial cells.
60 citations
TL;DR: Incremental PD could represent a novel therapeutic option for elderly patients with refractory HF, and correction of renal anemia, preservation of kidney function, and avoidance of high-dose diuretic therapy may play a role in maximizing clinical benefits.
57 citations
57 citations
TL;DR: Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases, and significant differences were seen by underlying diseases.
Abstract: Chronic kidney disease (CKD) can result from a wide variety of diseases, but whether clinical outcomes differ in the same CKD stages according to the underlying renal disease remains unclear. Clarification of this issue is important for stratifying risk of cardiovascular disease (CVD) and death in patients before dialysis. The study comprised 2,692 patients recruited from 11 outpatient nephrology clinics, classified by underlying disease of primary renal disease (PRD) (n = 1,306), hypertensive nephropathy (HN) (n = 458), diabetic nephropathy (DN) (n = 283), or other nephropathies (ON) (n = 645). Risks of events such as ischemic heart disease, congestive heart failure, stroke, and all-cause mortality within 12 months were examined by logistic regression analysis in each group. During the 12-months’ observation from recruitment, 200 cases were lost to follow-up, and 113 cases were introduced to chronic dialysis therapy. A total of 69 CVD events occurred (stroke in 27 cases), and 24 patients died. In total, increased odds ratios (OR) for the events by CKD stage (cf. CKD1 + 2: unadjusted) were CKD3, 1.29 [95% confidence interval (CI), 0.70–2.17]; CKD4, 2.73 (1.55–4.83); and CKD5, 4.66 (2.63–8.23). Regarding events in respective groups, no significant differences were seen by CKD stage except for the group with HN, but significant differences were seen by underlying diseases (cf. PRD: adjusted for confounding factors, including estimated glomerular filtration rate): HN, 2.57 (1.09–6.04); DN, 12.21 (3.90–38.20); and ON, 4.14 (1.93–8.89). Risk of CVD and mortality due to CKD needs to be stratified according to the underlying renal diseases.
53 citations
TL;DR: HSA‐redox is closely related to serious CVD incidence and mortality among HD patients, and shows a significantly lower value in patients with CVD than that without CVD.
Abstract: Human serum albumin is composed of human mercaptoalbumin (HMA) with cysteine residues having reducing powers and oxidized human non-mercaptoalbumin. The aim of this study is to clarify whether such redox state of albumin (HSA-redox) influences the incidence of cardiovascular disease (CVD) in chronic kidney disease patients on regular hemodialysis (HD). We measured HSA-redox using high-performance liquid chromatography in 86 anuric HD patients. The association between HSA-redox and incidental CVD events was evaluated. Twenty patients experienced symptomatic CVD events (16 patients died) at the 2-year follow-up. The fraction of HMA (f(HMA)) showed a significantly lower value in patients with CVD than that without CVD, in both pre-HD (36.5 ± 5.8% and 44.6 ± 9.8%, respectively) and post-HD (57.2 ± 6.2% and 67.2 ± 7.4%, respectively). The adjusted odds ratio (OR) for the incidental CVD event in patients with pre-HD f(HMA) < 40% was 5.0 (95% CI; 1.2 to 21.3), and that in patients with post-HD f(HMA) < 60% was 20.6 (3.2 to 134.7). Likewise, the adjusted OR for the CVD death in patients with pre-HD f(HMA) < 40% was 2.5 (0.6 to 12.5), and that in patients with post-HD f(HMA) < 60% was 25.6 (2.5 to 262.8). In conclusion, HSA-redox is closely related to serious CVD incidence and mortality among HD patients.
45 citations
TL;DR: CCr is closely associated with lacunar infarcts, suggesting that kidney dysfunction in the elderly is an independent risk factor or predictor for silent lacunars infarCTs.
Abstract: Background: No previous study has investigated the association of kidney dysfunction with silent lacunar infarcts and white-matter hyperintensity (WMH) independent of ambulatory blo
39 citations
TL;DR: CKD was significantly associated with MHT and WCHT on the basis of ABP monitoring compared with SNBP in the general Japanese population.
Abstract: Masked hypertension (MHT) is considered to be associated with organ damage, whereas the association of white-coat hypertension (WCHT) with organ damage remains controversial. Using home blood pressure measurements, we have previously reported that MHT is associated with a risk of chronic kidney disease (CKD) compared with sustained normal blood pressure (SNBP), although WCHT was not significantly related to CKD in a general Japanese population. The objective of this study was to examine CKD risk associated with WCHT and MHT as determined by ambulatory blood pressure (ABP) monitoring. Among 1023 residents in the general Japanese population of Ohasama, ABP and casual blood pressure (CBP) levels were recorded and blood and urine samples were collected. CKD was defined as a positive proteinuria and/or estimated glomerular filtration rate <60 ml min−1 per 1.73 m2. Participants were categorized into four groups using daytime ABP of 140/85 mm Hg and CBP of 140/90 mm Hg as cutoff points: SNBP, 60.0%; WCHT, 15.4%; MHT, 15.0%; and sustained hypertension (SHT), 9.6%. Odds ratios (ORs) for prevalence of CKD were calculated using a multiple logistic regression model. Compared with SNBP, risk of CKD was significantly higher in SHT (OR, 2.81; 95% confidence interval (CI), 1.66–4.75; P=0.0001), MHT (OR, 2.29; 95% CI, 1.45–3.63; P=0.0004) and WCHT (OR, 1.67; 95% CI, 1.03–2.71; P=0.0368). CKD was significantly associated with MHT and WCHT on the basis of ABP monitoring compared with SNBP in the general Japanese population.
Patent•
24 Nov 2010
TL;DR: In this paper, a method of evaluating and determining a dialysis membrane is proposed, which is conventionally indirectly carried out by measuring TACBUN (time averaged concentration of blood urea nitrogen), by detecting and quantitatively determining kidney failure substances including uremia substances, oxidative stress causing substances, substances accumulating in an autosomal dominant polycystic kidney.
Abstract: PROBLEM TO BE SOLVED: To provide a method of evaluating and determining a dialysis membrane, which is conventionally indirectly carried out by measuring TACBUN (time averaged concentration of blood urea nitrogen), by detecting and quantitatively determining kidney failure substances including uremia substances, oxidative stress causing substances, substances accumulating in an autosomal dominant polycystic kidney.SOLUTION: A dialysis membrane is evaluated by detecting or quantitatively determining kidney failure substances present in a test blood sample after hemodialysis. The kidney failure substances include cationic substances (1-methyladenosine, ophthalmic acid, creatinine, 3-methylhistidine, allantoin, trimethylamine-N-oxide, hydroxyproline, citrulline, methionine sulfoxide, asymmetric dimethylarginine, N,N-dimethylglycine, guanidinosuccinic acid, and the like) and anionic substances (cysteine-S-sulfuric acid, 4-hydroxy-3-methoxybenzoic acid, malonic acid, citraconic acid, citric acid, cis-aconitic acid, isocitric acid, 3-indoxyl sulfate, trans-aconitic acid, isethionate, pimelic acid, hippuric acid and the like).
TL;DR: In Table 2 of the above article (advance online publication 8 July 2010 and in the September issue 2010), 3- methylhistidin should have read 3-methylhistidine.
Abstract: Correction to: Hypertension Research (2010) 33, 945; doi:10.1038/hr.2010.113 In Table 2 of the above article (advance online publication 8 July 2010 and in the September issue 2010), 3-methylhistidin should have read 3-methylhistidine. The publishers apologize for this and are now happy to correct this mistake.