Takako Takita

Elevation of blood (1-->3)-beta-D-glucan concentrations in hemodialysis patients.

Determination of the blood (1→3)-β-D-glucan (β-DG) concentration is a sensitive marker to detect the presence of deep mycosis and fungal infections. Although cellulose material is known to contain β-DG, the influence of a cellulose dialyzer membrane on the blood β-DG level remains to be elucidated. In this study, we determined the plasma β-DG levels in dialysis outpatients using either a modified regenerated cellulose (MRC) or a synthetic polysulfone (PS) membrane for more than 3 months. Plasma β-DG levels were extremely high in patients using the MRC (2,778 ± 549 pg/ml, n = 9) but not the PS membrane (18.8 ± 3.7 pg/ml, n = 8) compared to normal ranges (<20 pg/ml). A single dialysis session using the MRC membrane further increased blood β-DG values to 5,561 ± 722 pg/ml (p < 0.01). After changing the membranes from MRC to PS, the blood β-DG levels gradually decreased and reached 29.6 ± 6.0 pg/ml at 6 months. In contrast, the PS membrane did not affect plasma β-DG levels after a single dialysis session (16.0 ± 3.9 pg/ml) or 4 months later (24.0 ± 4.9 pg/ml). These findings suggested that a cellulose membrane could influence the measurement of blood β-DG concentrations in the long-term. Careful assessment is required to diagnose the presence of fungal infection in HD patients using a cellulose membane.

Association of abdominal visceral adiposity and thigh sarcopenia with changes of arteriosclerosis in haemodialysis patients

BACKGROUND In haemodialysis (HD) patients, abdominal visceral fat is accumulated while lean body mass is decreased irrespective of their body mass indexes (BMI). However, it is poorly understood which changes of fat and muscle masses are more associated with changes of arteriosclerosis. We aimed at examining the associations of abdominal visceral fat and thigh muscle masses with markers of arteriosclerosis in chronic HD patients in a cross-sectional fashion. PATIENTS AND METHODS We measured abdominal visceral fat mass area (AVFA), abdominal subcutaneous fat mass area (ASFA), thigh muscle area (TMA) and TMA standardized for femoral shaft area (TMA/FSA) by computed tomography (CT) in 161 HD patients (age: 61 ± 11 years, time on HD: 12 ± 10 years, male/female = 113/48, non-diabetes/diabetes = 127/34). We also investigated carotid artery intima-media thickness (CA-IMT) using the ultrasound instrument, and brachial-ankle pulse wave velocity (baPWV), cardio-ankle vascular index (CAVI) and ankle-brachial pressure index (ABI) using the waveform device (CAVI-VaSera VS-1000). RESULTS AVFA was significantly and positively related to CA-IMT in both non-diabetic (r = 0.23, P < 0.05) and diabetic HD patients (r = 0.38, P < 0.05). There was a significant and positive correlation between AVFA and hs-CRP in all patients (r = 0.26, P < 0.01). ASFA was also significantly correlated with CA-IMT (r = 0.53, P < 0.01) in diabetic HD patients. TMA/SFA ratio was negatively associated with CA-IMT (r = - 0.21, P < 0.05), while positively with ABI (r = 0.28, P < 0.01) in non-diabetic patients. TMA/SFA ratio was inversely related to baPWV (r = - 0.41, P < 0.01) and CAVI (r = - 0.41, P < 0.05) in diabetic HD patients. Multiple regression analysis revealed that AVFA was a significant determinant of CA-IMT. TMA/AFA was also significantly associated with CA-IMT, baPWV, CAVI and ABI. CONCLUSION Accumulated abdominal visceral fat is associated with CA-IMT. In addition, reduced thigh muscle mass area is independently related to CA-IMT, baPWV, CAVI and ABI, suggesting that sarcopenia in the leg is closely associated with systemic changes of arteriosclerosis in HD patients.

Morphologic Abnormalities in the Brain of Chronically Hemodialyzed Patients without Cerebrovascular Disease

In this study, the authors evaluated the cerebral atrophy in 56 chronic hemodialyzed patients, who did not have clinical episodes or radiologic findings of cerebrovascular diseases, and 42 controls. Using computed tomography (CT) images, brain atrophy index (BAI), the proportion of subarachnoidal plus ventricular space in the cranial cavity, and ventricular area index (VAI), percent area of ventricle in the brain, were calculated. CT of the brain demonstrated an age-dependent increase in BAI in both hemodialyzed patients and controls. BAI and VAI were greater in hemodialyzed patients than healthy controls and the difference was significant at ages under 60 years in BAI and at ages less than 50 years in VAI. The atrophy of the frontal parts of the brain in patients on hemodialysis for 10 years or more was significantly greater than in patients dialyzed for less than 10 years. There was a significant negative correlation between BAI or VAI and hematocrit. These findings indicate that renal failure or hemodialysis itself might cause cerebral atrophy, and that the cerebral atrophy is more prominent in patients on hemodialysis for a long duration and with low hematocrit.

Comparison of serum albumin, C‐reactive protein and carotid atherosclerosis as predictors of 10‐year mortality in hemodialysis patients

Serum albumin, C‐reactive protein (CRP), and the intima‐medial thickness of the common carotid artery (CA‐IMT) are associated with clinical outcomes in hemodialysis (HD) patients. However, it remains unclear which parameters are more reliable as predictors of long‐term mortality. We measured serum albumin, CRP, and CA‐IMT in 206 HD patients younger than 80 years old, and followed them for the next 10 years. One hundred sixty‐eight patients (age: 57 ± 11 years, time on HD: 11 ± 7 years) were enrolled in the analyses. We divided all patients into three tertiles according to their albumin levels, and conducted multivariate analyses to examine the impact on 10‐year mortality. Seventy‐three (43.5%) patients had expired during the follow‐up. Serum albumin was significantly lower in the expired patients than in the surviving patients (3.8 ± 0.3 vs. 4.0 ± 0.3, P<0.01), while CRP (4.7 ± 5.0 vs. 2.8 ± 3.5 g/L, P=0.01) and CA‐IMT (0.70 ± 0.15 vs. 0.59 ± 0.11 mm, P<0.01) were significantly higher in the expired group. The multivariate analysis revealed that there was a significantly higher risk for total mortality in HD patients with serum albumin <3.8 g/dL (odds ratio 5.04 [95% CI: 1.30–19.60], P=0.02) when compared with those with albumin >4.1 g/dL. In contrast, CRP and CA‐IMT did not associate with total death. It follows from these findings that serum albumin is more superior as a mortality predictor compared with CRP and CA‐IMT in HD patients.

Relationship between an increased serum kynurenine/tryptophan ratio and atherosclerotic parameters in hemodialysis patients

Essential amino acid tryptophan (Trp) is mainly catabolized by indoleamine 2,3‐dioxygenase, which leads to the formation of kynurenine (Kyn). In this study, we reexamined whether an increased indoleamine 2,3‐dioxygenase activity, as estimated by the Kyn/Trp ratio (μM/mM), is associated with atherosclerotic parameters in hemodialysis (HD) patients. Serum Trp and Kyn were measured in 243 HD patients by liquid chromatography/electrospray ionization tandem mass spectrometry. We measured carotid artery intima‐medial thickness, brachial‐ankle pulse wave velocity, ankle‐brachial pressure index, and the cardio‐ankle vascular index. Log‐transformed Kyn/Trp ratio was significantly correlated with log‐transformed time on HD (ρ=0.28, P<0.01), log‐transformed highly sensitive C‐reactive protein (ρ=0.20, P<0.01), and peripheral total lymphocyte count (ρ=−0.13, P<0.05). A significant association was found between log‐transformed Kyn/Trp ratio and mean carotid artery intima‐medial thickness (ρ=0.18, P<0.01). Mean carotid artery intima‐medial thickness was significantly higher in the lowest quartile of Kyn/Trp ratio (<165) (0.62±0.12 mm) when compared with the highest quartile (≥304) (0.68±0.15 mm) (P<0.01). Ankle‐brachial pressure index was lower in the second quartile (1.01±0.20), the third quartile (1.01±0.19), and the fourth quartile (1.03±0.15) compared with that in the first quartile (1.09±0.13) (P<0.05). It follows from these findings that the Kyn/Trp ratio increases with time on HD, and is associated with advanced atherosclerotic changes in chronic HD patients.

Brachial-ankle pulse wave velocity and the cardio-ankle vascular index as a predictor of cardiovascular outcomes in patients on regular hemodialysis.

Brachial‐ankle pulse wave velocity (baPWV) and the cardio‐ankle vascular index (CAVI) are both used to evaluate arterial stiffness. The aim of the present study is to determine whether baPWV or CAVI is superior as a marker of arterial stiffness in hemodialysis (HD) patients. Of 194 patients, 59 patients had been excluded from the study due to advanced age over 76 years old (n = 29), or abnormal ankle‐brachial pressure index (ABI) (<0.90 or ≥1.30) (n = 30). We then followed the 135 patients (age: 60 ± 11 years, time on HD: 110 ± 93 months) for the 63 ± 4 (55–70) months. Thirty‐two (23.7%) patients had expired, 22 of them of cardiovascular (CV) causes. There were 37 fatal and non‐fatal CV events. Kaplan–Meier analysis revealed that the patients with the highest tertile of baPWV (≥16.6 m/s) had a significantly lower survival rate (P < 0.01) when compared with the second (13.4 ≤ baPWV < 16.6 m/s) and the lowest tertiles (<13.4 m/s). Cox hazards analysis after adjustment for comorbid risk factors revealed that the top tertile of baPWV was a determinant of CV death (hazards ratio [HR]: 16.9 [1.1–251.8], P < 0.05) In contrast, CAVI did not associate with CV mortality or events. These findings suggest that baPWV is superior to CAVI as a predictor of CV outcomes in patients on regular HD.

Abdominal Aortic Aneurysms in Hemodialysis Patients with Autosomal Dominant Polycystic Kidney Disease

Accessible online at: www.karger.com/journals/nef Dear Sir, Autosomal dominant polycystic kidney disease (ADPKD) is well known to be associated with a variety of life-threatening cardiovascular diseases such as intracranial and coronary aneurysms. The existence of an abdominal aorta aneurysm (AAA) [1–7] was also reported in some ADPKD patients with renal insufficiency. However, it remains unclear whether AAA may be one of the extrarenal complications in polycystic kidney disease. We investigated the abdominal aortic diameter in 261 patients: age 60 B 1 years, range 26–96 years; time on hemodialysis (HD) 11 B 0.4 years, range 1–29 years; male/female ratio 2/1. The patients were divided into three groups according to the renal diseases: group 1 had primary chronic glomerulonephritis (CGN, n = 201); group 2 diabetes mellitus (DM, n = 46), and group 3 had ADPKD (n = 14). Patients who had hypertensive nephrosclerosis were excluded from this study. The aortic diameter was measured at the maximally enlarged portion of the abdominal aorta using a slice of a computed tomography scan. An aortic aneurysm was defined as one measuring 3 cm or more in diameter, as described previously [8]. There were no differences in age and gender among the three groups, but the time on HD was significantly longer in the CGN patients (p ! 0.02). Significant differences were not found in atherosclerotic parameTable 1. Abdominal aortic diameter and atherosclerotic parameters (mean B SE)

Impact of Serum Parathyroid Hormone Concentration and Its Regulatory Factors on Arterial Stiffness in Patients Undergoing Maintenance Hemodialysis

Background: Cardiovascular mortality is extremely high in patients on hemodialysis. Among a variety of pathophysiological conditions, deranged calcium homeostasis including secondary hyperparathyroidism may be one of the factors contributing to cardiovascular disease in patients on hemodialysis. This study was designed to evaluate the role of the serum parathyroid hormone (PTH) concentration and its regulatory factors in serum on arterial stiffness in patients on maintenance hemodialysis. Methods: Arterial stiffness was assessed by pulse wave velocity (PWV) in 73 non-diabetic patients undergoing maintenance hemodialysis. At the same time, serum concentrations of calcium, phosphate, and intact PTH were measured. Results: Single regression analyses revealed that arterial PWV was positively correlated with age (r = 0.505, p < 0.0001), systolic blood pressure (r = 0.250, p = 0.043), and pulse pressure (r = 0.306, p = 0.012). It was inversely correlated with the serum phosphate concentration (r = –0.240, p = 0.041) and the duration of hemodialysis treatment (r = –0.343, p = 0.003), but not with serum concentrations of calcium and intact PTH or the calcium × phosphate product in serum. By multiple regression analysis age was found to be the most significant variable affecting arterial PWV, and the duration of hemodialysis treatment negatively influenced arterial PWV. Conclusion: Age is an independent risk factor for arterial stiffness in patients on maintenance hemodialysis, and the serum PTH concentration and its regulatory factors in the serum are not.

Blood Monocyte Count Is a Predictor of Total and Cardiovascular Mortality in Hemodialysis Patients

An increase in white blood cell (WBC) count is an independent predictor of mortality in hemodialysis (HD) patients. However, few studies have assessed the association of specific WBC subtypes with mortality. We prospectively studied the predictive value of WBC subtypes for total and cardiovascular death in 333 HD patients (age 63 ± 12 years; HD duration 129 ± 109 months) during a 40-month of follow-up. There was a significant and positive correlation between highly sensitive C-reactive protein and neutrophil (r = 0.28, p < 0.01) and monocyte (r = 0.20, p < 0.01) counts by a non-parametric Spearman rank analysis. Blood monocyte counts were significantly correlated inversely with ankle-brachial pressure index (r = –0.24, p < 0.01). Kaplan-Meier analysis revealed that basal neutrophil (>4,060/μl) and monocyte (>270/μl) counts in the highest tertile had a significantly lower survival rate compared to the middle and the lowest tertiles, respectively (p < 0.03). Cox hazards analysis after adjustment for other conventional risk factors revealed that monocyte counts of >270/μl became a determinant of total death compared with those of <180/μl (hazards ratio 1.98 [1.10–3.57], p = 0.02). In contrast, neutrophil and lymphocyte counts were not associated with mortality. Our findings suggest that an increased blood monocyte count is an independent predictor of long-term mortality in chronic HD patients.

A Comparison of Systemic Inflammation-Based Prognostic Scores in Patients on Regular Hemodialysis

Background/Aims: Systemic inflammation-based prognostic scores have prognostic power in patients with cancer, independently of tumor stage and site. Although inflammatory status is associated with mortality in hemodialysis (HD) patients, it remains to be determined as to whether these composite scores are useful in predicting clinical outcomes. Methods: We calculated the 6 prognostic scores [Glasgow prognostic score (GPS), modified GPS (mGPS), neutrophil-lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), prognostic index (PI) and prognostic nutritional index (PNI)], which have been established as a useful scoring system in cancer patients. We enrolled 339 patients on regular HD (age: 64 ± 13 years; time on HD: 129 ± 114 months; males/females = 253/85) and followed them for 42 months. The area under the receiver-operating characteristics curve was used to determine which scoring system was more predictive of mortality. Results: Elevated GPS, mGPS, NLR, PLR, PI and PNI were all associated with total mortality, independent of covariates. If GPS was raised, mGPS, NLR, PLR and PI were also predictive of all-cause mortality and/or hospitalization. GPS and PNI were associated with poor nutritional status. Using overall mortality as an endpoint, the area under the curve (AUC) was significant for a GPS of 0.701 (95% CI: 0.637-0.765; p < 0.01) and for a PNI of 0.616 (95% CI: 0.553-0.768; p = 0.01). However, AUC for hypoalbuminemia (<3.5 g/dl) was comparable to that of GPS (0.695, 95% CI: 0.632-0.759; p < 0.01). Conclusion: GPS, based on serum albumin and highly sensitive C-reactive protein, has the most prognostic power for mortality prediction among the prognostic scores in HD patients. However, as the determination of serum albumin reflects mortality similarly to GPS, other composite combinations are needed to provide additional clinical utility beyond that of albumin alone in HD patients.