Biomedical subjects

Yuhei Kawano

Publications and source records attributed to Yuhei Kawano.

At least 37 records · Page 2Linked to original sources

PubMed2005

Chronic administration of adrenomedullin attenuates the hypertension and increases renal nitric oxide synthase in Dahl salt-sensitive rats.

Adrenomedullin reduces systemic blood pressure and increases urinary sodium excretion partly through the release of nitric oxide. We hypothesized that chronic adrenomedullin infusion ameliorates salt-sensitive hypertension and increases the expression of renal nitric oxide synthase (NOS) in Dahl salt-sensitive (DS) rats, because the reduced renal NOS expression promotes salt sensitivity. DS rats and Dahl salt-resistant (DR) rats were fed a high sodium diet (8.0% NaCl) for 3 weeks. The high sodium diet resulted in an increase in blood pressure and a reduction of urinary sodium excretion in association with increased renal adrenomedullin concentrations and decreased expression of renal neuronal NOS (nNOS) and renal medullary endothelial NOS (eNOS) in DS rats compared with DR rats. Chronic adrenomedullin infusion partly inhibited the increase of blood pressure and proteinuria in association with a restoration of renal nNOS and medullary eNOS expression in DS rats under the high sodium diet. The immunohistochemical analysis revealed that the restored renal nNOS expression induced by chronic adrenomedullin infusion may reflect the restoration of nNOS expression in the macula densa and inner medullary collecting duct. These results suggest that adrenomedullin infusion has beneficial effects on this hypertension probably in part through restored renal NOS expression in DS rats.

Adrenomedullin↗

PubMed2005

A novel immunosuppressant FTY720 ameliorates proteinuria and alterations of intrarenal adrenomedullin in rats with autoimmune glomerulonephritis.

FTY720 has been originally developed as a new immunosuppressive agent, which prolongs graft survival in organ transplantation. Adrenomedullin (AM) participates in the regulation of sodium homeostasis and has renoprotective effects. The possible involvement of renal AM in the pathophysiology of glomerulonephritis (GN) and the effect of FTY720 has been evaluated in rats. HgCl2 (1 mg/kg body weight) was inoculated subcutaneously 3 times/week for a total of 2 weeks. FTY720 (3 or 10 mg/kg) was inoculated subcutaneously daily. The proteinuria, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum total cholesterol levels were increased and serum albumin level was reduced in rats with HgCl2-induced GN compared with controls. FTY720 reduced proteinuria (3 mg/kg: -25%; 10 mg/kg: -41%), urinary NAG excretion (-11%; -52%) and total cholesterol level (-21%; -55%) in a dose-dependent manner. Renal AM level and its mRNA expression were increased in rats with GN compared with controls (Peptide Cortex: +69%; Medulla: +82%; mRNA Cortex: +25%). Interestingly, FTY720 additionally increased these levels (Peptide Cortex: +38%; Medulla: +39%; mRNA Cortex: +20%). Renal AM levels correlated with urinary NAG excretion and creatinine clearance. These results suggest that FTY720 suppresses the renal damage in rats with GN and renal AM may participate in the pathophysiology of GN and the renoprotective effects of FTY720.

Adrenomedullin↗

PubMed2005

Upregulation of intracardiac adrenomedullin and its receptor system in rats with volume overload-induced cardiac hypertrophy.

Specific adrenomedullin receptors have been identified as calcitonin receptor-like receptor (CRLR)/receptor activity-modifying proteins (RAMP2 and RAMP3) complexes. Although we have demonstrated that adrenomedullin is increased in volume overload-induced cardiac hypertrophy, it remains unknown whether the adrenomedullin receptor is altered or not. This study sought to investigate the significance of intracardiac adrenomedullin and its receptor system in volume overload-induced cardiac hypertrophy. Left ventricular adrenomedullin levels were higher in aortocaval shunt (ACS) rats than in controls (+58%). The left ventricular gene expressions of adrenomedullin, CRLR, RAMP2 and RAMP3 were increased (+27%, +76%, +108% and +131%, respectively) and the left ventricular collagen gene expressions were also increased (type I: +138%, type III: +87%). The left ventricular adrenomedullin level correlated with the gene expression of type III collagen (R=0.42). These results suggest that intracardiac adrenomedullin and its receptor system are upregulated and may participate in the regulation of cardiac remodeling in volume overload-induced cardiac hypertrophy.

Adrenomedullin↗

PubMed2005

Production and autocrine/paracrine effects of endogenous insulin-like growth factor-1 in rat cardiac fibroblasts.

Insulin-like growth factor (IGF)-1 appears to play an important role in cardiac hypertrophy or remodeling. However, the role of endogenous IGF-1 in the growth of cardiac myocytes and fibroblasts remains unclear. This study investigated the major site of the production of cardiac IGF-1 and the local effects of endogenous IGF-1 secreted from cardiac cells. A significant expression of IGF-1 mRNA was found in cultured neonatal and adult rat cardiac fibroblasts, but not in myocytes. In addition, an in vivo examination by in situ hybridization histochemical analyses demonstrated the IGF-1 transcripts in the interstitial fibrotic tissue of the ventricle. Time-dependent secretion of IGF-1 protein was also observed in cultured cardiac fibroblasts. An antibody against IGF-1 decreased collagen synthesis in cardiac fibroblasts under basal conditions. Fibroblast-conditioned medium, as well as exogenous IGF-1, increased protein synthesis in cardiac myocytes, and this increase was inhibited by antibodies against IGF-1 and IGF-1 receptor, IGF binding protein-3, and IGF-1 receptor antagonist. These observations suggest that IGF-1 is produced and released mainly from cardiac fibroblasts and that endogenous IGF-1 promotes collagen synthesis by cardiac fibroblasts and hypertrophy of myocytes as an autocrine and a paracrine factor. Cardiac IGF-1 may function as an endogenous modulator of cardiac hypertrophy or remodeling.

Animals↗

PubMed2005

Asymptomatic renal infarction, due to fibromuscular dysplasia, in a young woman with 11 years of follow-up.

We report a 27-year-old woman with renovascular hypertension, renal infarction, and hepatic artery aneurysm due to fibromuscular dysplasia. The patient was first noted to have renal artery aneurysm and hepatic artery aneurysm at the age of 17. The renal infarction was asymptomatic and was incidentally detected by magnetic resonance imaging (MRI) examination. Because of the rather peripheral location of the aneurysms, percutaneous transluminal renal artery angioplasty was considered inappropriate. This case suggests the need for long-term and periodical follow-up of patients with fibromuscular dysplasia.

Adult↗

PubMed2005

Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy and diastolic dysfunction, which are common cardiac consequences of hypertension, are modified by insulin resistance. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse such cardiac changes in hypertensive patients. METHODS: A total of 30 patients with essential hypertension were enrolled in this study. In echocardiographic examinations, LV mass index, the peak velocity ratio of early diastolic to atrial filling (E/A), and the E-wave deceleration time (DcT) were determined. Insulin sensitivity test with steady-state plasma glucose (SSPG) method, oral glucose tolerance test, and blood samplings for measurement of adiponectin and matrix metalloproteinase (MMP)-2 were also performed. Six months after treatment with pioglitazone (30 mg/day), an insulin sensitizer, these examinations were repeated. RESULTS: Pioglitazone significantly increased E/A and decreased DcT, without a change in LV mass index. These improvements in diastolic properties were much greater in subjects with a marked (>or==3.3 mmol/L) decrease in SSPG (n=11) than the others (n=19), although the decrease in glucose levels did not differ between the two groups. In addition, the changes in E/A and DcT were closely correlated with the decrease in SSPG. Pioglitazone treatment significantly elevated plasma adiponectin and MMP-2 levels, and the increase in MMP-2 was positively correlated with the increase in adiponectin. CONCLUSIONS: The present findings demonstrate that pioglitazone improves LV diastolic function without LV mass regression in hypertensive patients in proportion to the amelioration of insulin resistance. These findings suggest that increased adiponectin and MMP may be involved in the beneficial effect of pioglitazone on diastolic function.

Adiponectin↗

PubMed2005

Pioglitazone-induced insulin sensitization improves vascular endothelial function in nondiabetic patients with essential hypertension.

BACKGROUND: It has been suggested that insulin resistance is involved in the impaired vascular endothelial function not only in diabetic patients but also in hypertensive patients. The present study assessed the hypothesis that primary treatment of insulin resistance may reverse endothelial dysfunction in hypertensive subjects. METHODS: Fifteen nondiabetic patients with essential hypertension were enrolled in this study. An oral glucose tolerance test (OGTT) and insulin sensitivity test were performed. Insulin sensitivity was determined with the steady-state plasma glucose (SSPG) method. Only subjects with insulin resistance (SSPG > or =8.3 mmol/L) were included. Endothelium-dependent vasodilation during reactive hyperemia (flow-mediated dilation) was evaluated using ultrasonography. Six months after treatment with the insulin-sensitizing agent pioglitazone (30 mg/day), these examinations were repeated in all subjects. RESULTS: Pioglitazone did not decrease fasting plasma glucose and hemoglobin A1c (HbA1c) in the nondiabetic subjects, although the area under the curve for glucose and insulin on OGTT significantly decreased. A marked decrease in SSPG was observed after pioglitazone treatment (10.7 +/- 1.4 to 7.9 +/- 2.1 mmol/L, P < .001). Endothelium-dependent vasodilation evaluated by flow-mediated dilation was also improved by pioglitazone (5.0% +/- 2.2% to 6.3% +/- 2.4%, P = .023). Furthermore, the increase in flow-mediated dilation was closely correlated with the decrease in SSPG (r = 0.72, P = .002) but not with the decrease in area under the curve for glucose or insulin on OGTT. Endothelium-independent dilation induced by glyceryl trinitrate was not altered by pioglitazone. CONCLUSIONS: The present findings demonstrate that pioglitazone improves endothelial function in nondiabetic hypertensive individuals with insulin resistance, and that the improvement is associated with the amelioration of insulin resistance itself rather than that of hyperglycemia or hyperinsulinemia.

Aged↗

PubMed2005

Hypertension susceptibility genes on chromosome 2p24-p25 in a general Japanese population.

BACKGROUND: Genome-wide scans from Italy and China suggest a hypertension-susceptible locus between D2S2278 (nucleotides 11,245,080 - 11,245,358) and D2S168 (nucleotides 11,467,214 - 11,467,422) on chromosome 2. METHODS: We performed a large association study of polymorphisms in this region with blood pressure modulation in a Japanese general population. Forty-seven polymorphisms in 14 genes between nucleotide 8,845,292 and nucleotide 11,946,689, which contains D2S2278 and D2S168, were genotyped in 1880 individuals, 796 of whom were hypertensive and 1084 normotensive. RESULTS: Multivariate logistic regression analysis with adjustment for age, body mass index, presence of hyperlipidemia, diabetes mellitus, and current smoking and drinking revealed that one single nucleotide polymorphism (SNP), IMS-JST126186, in HPCAL1 (hippocalcin-like 1) in women and two SNPs, IMS-JST149391 and IMS-JST149390, in GREB1 (gene regulated by estrogen in breast cancer 1) in men were significantly associated with both prevalence of hypertension and blood pressure levels. To examine the role of GREB1 in more detail, we identified 38 additional genetic variations in GREB1 by direct sequencing, and eight polymorphisms were genotyped. One SNP, 45718A>G, was significantly associated with hypertension and blood pressure level in men, and this SNP was in linkage disequilibrium with a SNP present at the 3' splice site of intron 11. CONCLUSION: Our study suggests that GREB1 and HPCAL1 are candidate hypertension-susceptibility genes in the Japanese general population and supports previous studies that also identified hypertension-related loci in this narrow region.

Adult↗

PubMed2005

Genetic variations of regulator of G-protein signaling 2 in hypertensive patients and in the general population.

OBJECTIVES: Mice deficient in the regulator of G-protein signaling 2 (RGS2) exhibit a strong hypertensive phenotype. We studied whether genetic variations in RGS2 are implicated in hypertension or other phenotypes in Japanese hypertensive individuals and the general population. METHODS: We sequenced all exons of RGS2 and the promoter region in 953 and 48 hypertensive individuals, respectively. Genotyping by the TaqMan polymerase chain reaction method was performed for six missense or frameshift mutations and common single nucleotide polymorphisms in the general population, with a sample size of 1872 individuals (862 men and 1011 women). RESULTS: We identified five novel missense mutations (Q2L; n = 2, Q2R; n = 1, M5V; n = 1, R44H; n = 2, Q78H; n = 1) and one novel frameshift mutation (1925-1926insT; n = 2) in a heterozygous state, in addition to 33 variations including five common single nucleotide polymorphisms. Six missense/frameshift mutations and three common single nucleotide polymorphisms (-638A > G, 1026T > A, 1891-1892delTC) were successfully genotyped in the general population. Mutations Q2L (n = 2), M5V (n = 1), and 1925-1926insT (n = 2) were only identified in hypertensive subjects. Six out of seven individuals with the R44H mutation, which occurs in the amphipathic alpha-helical domain of RGS2, had hypertension. The results showed a significant association of two common single nucleotide polymorphisms, 1026T > A [TT versus TA + AA: odds ratio (OR) 1.33; 95% confidence interval (CI) 1.02-1.74; P = 0.035] and 1891-1892delTC (I: insertion allele, D: deletion allele, II versus ID + DD: OR 1.47; 95% CI 1.09-1.97; P = 0.012), with hypertension in women by multivariate logistic regression analysis. CONCLUSION: Our results suggest that genetic variations in RGS2 contribute partly to the hypertensive phenotype.

Aged↗

PubMed2005

QTc dispersion in haemodialysis patients with cardiac complications.

BACKGROUND AND AIMS: QTc dispersion (Maximum - Minimum QTc interval on a standard 12-lead electrocardiogram (ECG)) is a useful predictor of tachyarrhythmic events and related sudden cardiac death. Recent studies have reported that QTc dispersion is prolonged in patients receiving haemodialysis (HD), and it is often further prolonged following HD treatment. In the present study, we examine whether the patients who are susceptible to prolongation of QTc dispersion by HD are prone to life-threatening cardiovascular events and related deaths. METHODS: Forty-eight patients with cardiac symptoms such as chest pain (n = 32), arrhythmia (n = 2) or heart failure (n = 14) and receiving chronic HD treatment (40 males and eight females) were subjected to the present study. Twenty-six of a total 48 patients were given a diagnosis of ischaemic heart disease (IHD) by coronary angiography. Ten patients had cerebrovascular accidents and 11 patients had peripheral vascular disease. After the ECG recording, a prospective follow up was conducted for 37 +/- 24 months. RESULTS: During the follow-up period, 30 patients had cardiac events, and 23 including 18 cardiovascular deaths occurred as outcomes. Throughout the total period, patients who showed prolongation of QTc dispersion after HD had cardiovascular deaths with higher incidence than those did not show the prolongation. CONCLUSIONS: We consider that prolongation of QTc dispersion after HD treatment can predict the prognosis of patients with renal failure bearing cardiac complications. Great care is necessary for such patients if they show longer QTc dispersion and/or susceptibility for further prolongation after HD treatment.

Adult↗

PubMed2005

Adrenomedullin reflects cardiac dysfunction, excessive blood volume, and inflammation in hemodialysis patients.

BACKGROUND: Plasma adrenomedullin (AM) reflects cardiac dysfunction and predicts survival after myocardial infarction. The present study was designed to investigate whether the mature AM (mAM) reflects status of cardiac function, systemic blood volume, or inflammation in hemodialysis patients with cardiovascular disease, and whether mortality and additional cardiovascular morbidity can be predicted by mAM. METHODS: Plasma levels of mAM, atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), norepinephrine (NE), and C-reactive protein (CRP) before hemodialysis were measured in 67 chronic hemodialysis patients with cardiovascular disease, along with 2-dimensional and Doppler echocardiographic variables. RESULTS: By univariate regression analysis, mAM correlated negatively with pulmonary venous flow velocity ratio and left ventricular (LV) ejection fraction and positively with LV inflow velocity ratio, LV end-diastolic, end-systolic volume indexes, plasma CRP level, and removal fluid volume by ultrafiltration. Multivariate stepwise regression analysis revealed that mAM reflected all variables better than log [ANP], log [BNP], and log [NE]. During a 1-year follow-up period, 7 patients died and 8 had additional cardiovascular events. Event-free Kaplan-Meier curves based on the median mAM (4.55 pmol/L) showed that patients with high plasma mAM levels had higher mortality and morbidity than those with low plasma mAM levels (P = 0.0056). By Cox multivariate proportional hazard analysis, mAM was related to mortality and morbidity [hazard ratio (HR) 4.55, 95% CI 1.2-16.8, P= 0.023). CONCLUSION: Plasma mAM reflects cardiac dysfunction, excessive blood volume, and inflammation better than ANP, BNP, and NE, resulting in a predictor of mortality and cardiovascular morbidity in hemodialysis patients with cardiovascular disease.

Adrenomedullin↗

PubMed2005

Primary aldosteronism combined with preclinical Cushing's syndrome in an elderly patient.

Pre-clinical Cushing's syndrome (pre-CS) is sometimes seen with adrenal cortical tumors. An 80-year-old woman had severe hypertension and hypokalemia, the typical clinical features of primary aldosteronism, but detailed hormonal examinations revealed the accompanying pre-CS. After adrenalectomy by laparoscopy, her blood pressure was remarkably reduced and the hypokalemia also recovered. The tumor consisted of mostly light clear cells and scattered dark compact cells resembling islands. Abundant expression of cytochrome P450 aldosterone synthase in the clear cells and cytochrome P450 11beta-hydroxylase in the dark cells was detected by immunohistochemical studies, which confirmed that clear cells can produce aldosterone and compact cells can produce cortisol.

Adrenal Cortex Neoplasms↗

PubMed2005

Single nucleotide polymorphisms in the interleukin-6 gene associated with blood pressure and atherosclerosis in a Japanese general population.

It is known that increased plasma levels of inflammatory markers, such as interleukin-6 (IL-6), are associated with atherosclerosis and myocardial infarction. The aim of this study was to reveal the contribution of the single nucleotide polymorphisms (SNPs) of the IL-6 gene on the blood pressure regulation and progression of atherosclerosis in a general Japanese population. In order to evaluate the potential implications of genetic variability of the IL-6 gene, we explored eight SNPs by direct sequencing for the entire coding region and the promoter region in the IL-6 gene and genotyped two SNPs, -636G > C in the promoter region and 1691C > G in intron 3, for a total of 2,421 Japanese subjects (1,162 men and 1,259 women). As a consequence, -636 G > C was significantly associated with systolic blood pressure (SBP) and carotid intima-media thickness (IMT) in women, and 1691C > G showed a relationship with SBP and carotid IMT in men after adjustment for all confounding factors. Although neither SNP had a significant correlation to the prevalence of hypertension, the haplotype frequency analysis indicated that the number of hypertensive men with a G allele at both -636 and 1691 was significantly greater than the number of nonhypertensive men with this combination. Thus, these two SNPs in the promoter region and intron 3 of the IL-6 gene might play a role in the blood pressure regulation and progression of atherosclerosis in the Japanese.

Aged↗

PubMed2005

A novel missense mutation, F826Y, in the mineralocorticoid receptor gene in Japanese hypertensives: its implications for clinical phenotypes.

A gain-of-function mutation resulting in the S810L amino acid substitution in the hormone-binding domain of the mineralocorticoid receptor (MR, locus symbol NR3C2) is responsible for early-onset hypertension that is exacerbated in pregnancy. The objective of this study was to test whether other types of missense mutations in the hormone-binding domain could be implicated in hypertension in Japanese. Here, we screened 942 Japanese patients with hypertension for the S810L mutation in exon 6 in the MR. We did not identify the S810L mutation in our hypertensive population, indicating that S810L does not play a major role in the etiology of essential hypertension in Japanese. However, we identified a novel missense mutation, F826Y, in three patients in a heterozygous state, in addition to four single nucleotide polymorphisms, including one synonymous mutation (L809L). The F826Y mutation is present in the MR hormone-binding domain and might affect the ligand affinity. The F826Y mutation was also identified in 13 individuals (5 hypertensives and 8 normotensives) in a Japanese general population (n=3,655). The allele frequency was 0.00178. The frequencies of the F826Y mutation in the hypertensive population (3/942) and in the hypertensive group (5/ 1,480) and the normotensive group (8/2,175) in the general population were not significantly different, suggesting that this mutation does not greatly affect hypertension. Although it is unclear at present whether or not the F826Y mutation makes a substantial contribution to the mineralocorticoid receptor activity, this missense mutation may contribute, to some extent, to clinical phenotypes through its effects on MR.

Aged↗

PubMed2005

Clinical implications of assessing coronary flow velocity reserve and plasma endothelin-1 in hypertensive patients.

Previous reports have indicated that hypertensive patients who have angina-like chest pain and normal coronary arteriograms have reduced coronary flow velocity reserve (CFVR) levels. In addition, elevated plasma endothelin-1 (ET-1) levels have been reported to be associated with microvascular angina. The purpose of this study was to evaluate the plasma ET-1 levels and CFVR in patients with chest pain but without coronary artery disease (CAD). A total of 66 patients were included in this study. CAD was ruled out by exercise stress test or coronary angiogram. Plasma ET-1 and CFVR measurements were performed in patients with (n=35) and without (n=31) a history of angina-like chest pain. CFVR was measured using adenosine-triphosphate stress transthoracic Doppler echocardiography. The mean ET-1 level was significantly higher and the CFVR was significantly lower in patients in the symptomatic group than in those in the asymptomatic group (ET-1: 3.85 +/- 1.24 pg/ml vs. 2.98 +/- 1.27 pg/ml, CFVR: 2.26 +/- 0.48 vs. 2.77 +/- 0.11, respectively). Plasma ET-1 level and CFVR were significantly correlated with each other (-r = 0.265, p = 0.033). Age, blood pressure, cardiovascular risk factors, and left ventricular mass index were similar between the two groups. The results of multiple regression analysis indicate that age (p = 0.008) and plasma ET-1 concentration (p = 0.031) had statistically independent associations with CFVR. Attenuated CFVR in the symptomatic hypertensive patients was associated with endothelial dysfunction, which results in elevated plasma ET-1 levels. The link between these two parameters may play a role in the genesis of chest pain in hypertensive patients without CAD.

Aged↗

PubMed2005

[Age related hemodynamic changes in the elderly].

Systolic blood pressure (SBP) increases by aging. In contrast, diastolic blood pressure (DBP) decreases after age 60 because of lowering aortic compliance. Therefore, isolated systolic hypertension (ISH) is common in the elderly. ISH is a risk for cardiovascular complications, and induces a left ventricular hypertrophy combined with diastolic dysfunction. Diastolic heart failure followed by diastolic dysfunction is more common than systolic heart failure in the elderly. Furthermore, changes in neuroendocrine systems by aging may lead orthostatic hypotension, non-dipping status, large blood pressure variability, and reduced heart rate variability. In the management of elderly hypertension, the understanding for these age-related hemodynamic changes is very important.

Aged↗

PubMed2005

Life-threatening hyperkalemia during a combined therapy with the angiotensin receptor blocker candesartan and spironolactone.

We describe a hypertensive nephrosclerosis patient presenting with severe hyperkalemia due to a combination therapy of the angiotensin receptor blocker (ARB) candesartan and spironolactone despite mildly decreased renal function. Recently, ARBs are replacing the ACE inhibitors. The combined therapy with ARB and spironolactone will eventually become the standard regimen. The strict attention and close monitoring of serum potassium should be mandatory in combination therapy to prevent hyperkalemia. Assessment of trans-tubular potassium gradient (TTKG) and fractional excretion of potassium (FEK) before starting the therapy would help in identifying the patients at higher risk of developing hyperkalemia. Co-administration of thiazide or loop diuretics is recommended to reduce the risk of hyperkalemia.

Angiotensin II Type 1 Receptor Blockers↗

PubMed2004

Orthostatic hypotension at the introductory phase of haemodialysis predicts all-cause mortality.

BACKGROUND: Since the predictive value of orthostatic hypotension (OH) at the introductory phase of haemodialysis (HD) is unknown, we examined the association between OH and all-cause death in patients who started HD between 1987 and 2001. METHODS: More than three consecutive blood pressure measurements before HD treatments (pre-HD BP) were made on each of 304 patients who had recently been started on HD and were in a stable condition. OH was defined as a drop in systolic BP of >20 mmHg or in diastolic BP of >10 mmHg after standing. RESULTS: Of 304 patients, 42% had OH. OH was significantly associated with pre-HD supine systolic BP; its severity was significantly associated with a past history of cerebrovascular disease and pre-HD supine systolic BP. During a mean follow-up of 4.0+/-3.0 years (range 0.1-13.2 years), 136 deaths were recorded. A multivariate Cox proportional hazards model analysis demonstrated that OH and a past history of cerebrovascular disease were independent predictors of all-cause death. The comparison by Kaplan-Meier analysis of the overall survival of patients with and without OH was significant. CONCLUSIONS: Our findings validate OH at the introductory phase of HD as a novel independent predictor of all-cause mortality among HD patients.

Aged↗