Yoshihiro Tsujimoto

Impact of Glycemic Control on Survival of Diabetic Patients on Chronic Regular Hemodialysis: A 7-Year Observational Study

OBJECTIVE—To investigate the impact of glycemic control during regular hemodialysis on the survival of diabetic patients with chronic kidney disease (CKD) in a longitudinal observational study. RESEARCH DESIGN AND METHODS—A total of 114 diabetic CKD patients on hemodialysis at Inoue Hospital (Suita, Japan) were surveyed from May 1995 to December 2002 (survey period 45.5 ± 29.3 [means ± SD] months). All subjects were categorized into three groups by mean HbA1c (A1C) level during the 3-month period on hemodialysis preceding entry, as follows: good (A1C <6.5%, 5.7 ± 0.4%, n = 34), fair (6.5 ≤ A1C < 8.0%, 7.2 ± 0.4%, n = 39), and poor (A1C ≥8.0%, 9.2 ± 0.9%, n = 41) A1C groups. RESULTS—There were no significant differences in age at entry, initiation of hemodialysis, duration of hemodialysis, blood pressure, cardiothoracic ratio, serum creatinine level, or hemoglobin level among the three groups. The cumulative survival of the poor A1C group during the survey was significantly lower than that of the fair and good A1C groups as determined by Kaplan-Meier estimation (P = 0.041, log-rank test). In a multivariate Cox proportional hazard model, both poor A1C group (hazard ratio 2.889, P = 0.010) and mean A1C (1.260 per 1.0%, P = 0.003) were significant predictors of survival. CONCLUSIONS—In diabetic CKD patients on regular hemodialysis, poor glycemic control is an independent predictor of prognosis. This finding indicates the importance of careful management of glycemic control even after initiation of hemodialysis.

Fatigue Is a Predictor for Cardiovascular Outcomes in Patients Undergoing Hemodialysis

BACKGROUND AND OBJECTIVES Despite potential significance of fatigue and its underlying components in the occurrence of cardiovascular diseases, epidemiologic data showing the link are virtually limited. This study was designed to examine whether fatigue symptoms or fatigues underlying components are a predictor for cardiovascular diseases in high-risk subjects with ESRD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS 788 volunteer patients under hemodialysis therapy (506 male, 282 female) completed the survey between October and November 2005, with the follow-up period up to 26 months to monitor occurrence of fatal or nonfatal cardiovascular events. The questionnaire consisted of 64 questions, and promax rotation analysis of the principal component method conceptualized eight fatigue-related factors: fatigue itself, anxiety and depression, loss of attention and memory, pain, overwork, autonomic imbalance, sleep problems, and infection. RESULTS 14.7% of the patients showed fatigue scores higher than twice the SD of the mean for healthy volunteers. These highly fatigued patients exhibited a significantly higher risk for cardiovascular events (hazard ratio: 2.17; P < 0.01), with the relationship independent of the well-known risk factors, including age, diabetes, cardiovascular disease history, and inflammation and malnutrition markers. Moreover, comparisons of the risk in key subgroups showed that the risk of high fatigue score for cardiovascular events was more prominent in well-nourished patients, including lower age, absence of past cardiovascular diseases, higher serum albumin, and high non-HDL cholesterol. CONCLUSIONS Fatigue can be an important predictor for cardiovascular events in patients with ESRD, with the relationship independent of the nutritional or inflammatory status.

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.

Leptin in peritoneal dialysate from continuous ambulatory peritoneal dialysis patients.

The adipocyte-derived hormone leptin is the 16-kd product of the ob gene that regulates food intake and body weight. Plasma leptin level is elevated in patients with chronic renal failure, partly because of impaired clearance through the kidney. In this study, we examined whether leptin is cleared into peritoneal dialysate in patients with end-stage renal disease treated by continuous ambulatory peritoneal dialysis (CAPD). The subjects were 46 CAPD patients and 67 age- and gender-matched healthy subjects. Leptin concentration in peritoneal dialysate from CAPD patients was measurable by a sensitive enzyme-linked immunosorbent assay (ELISA), and the daily loss of leptin by the peritoneal route was estimated to correspond to the amount contained in approximately 2 L plasma. Dialysate leptin concentration correlated positively with plasma leptin level and with percent body fat measured by dual-energy X-ray absorptiometry. The dialysate-to-plasma (D/P) ratio of leptin concentration was twice higher than expected from its molecular weight. D/P ratios of beta2-microglobulin, albumin, and transferrin showed strong correlations with each other (r = 0.768 to 0.801), whereas the correlation between D/P ratios of leptin and beta2-microglobulin was less impressive (r = 0.378). This was also the case with the relationship between apparent peritoneal clearances of these macromolecules, suggesting that dialysate leptin had some origins other than passive transport of plasma leptin. To test the hypothesis that abdominal visceral fat may contribute to the unexpectedly raised peritoneal dialysate leptin concentration, multiple regression analysis was performed. Leptin concentration in peritoneal dialysate showed significant association with plasma leptin level and D/P ratio of beta2-microglobulin, and it also showed an independent association with abdominal visceral fat but not with subcutaneous fat assessed by ultrasonography. These results showed that peritoneal dialysate from CAPD patients contained a significant amount of leptin, which derived presumably from both plasma and local visceral fat tissue.

Trace Elements in the Hair of Hemodialysis Patients

Trace element disturbance is often observed in hemodialysis patients. While trace element concentrations have been reported in blood samples from hemodialysis patients, they have not been well investigated in scalp hair. In the present study, 22 trace elemental concentrations were measured by inductively coupled plasma-atomic emission spectrometry in the scalp hair of 80 male hemodialysis patients and compared with those of 100 healthy male subjects. In hemodialysis patients, the concentrations of beryllium, arsenic, magnesium, chromium, manganese, iron, selenium, molybdenum, iodine, vanadium, and cobalt were significantly higher than those in healthy subjects, while lead, mercury, copper, germanium, and bromine were significantly lower than those in the former group. No significant differences were observed for lithium, aluminum, cadmium, zinc, boron, or nickel. There were significant positive correlations between the duration of hemodialysis and the magnesium and manganese concentrations. There was a significant negative correlation between cadmium concentration and the duration of hemodialysis. There were significant positive correlations between dialysis efficacy (Kt/V) and magnesium, manganese, zinc, and selenium concentrations. In conclusion, trace element concentrations of the scalp hair are different between hemodialysis patients and healthy subjects. Essential trace elements, such as magnesium, manganese, zinc, and selenium, may be affected by the duration of hemodialysis and Kt/V.

Dialysis modality is independently associated with circulating endothelial progenitor cells in end-stage renal disease patients

BACKGROUND Numbers of endothelial progenitor cells (EPC) have been shown to be decreased in subjects with end-stage renal disease (ESRD). It is not clear, however, whether dialysis modality affects circulating EPCs in ESRD subjects. METHODS We examined the number of circulating EPCs in 67 continuous ambulatory peritoneal dialysis (CAPD) patients and age- and gender-matched 142 haemodialysis (HD) patients, and 78 subjects without chronic kidney disease. Arterial stiffness was analysed as pulse-wave velocity (PWV) for these patients, and their mutual relationship with circulating EPCs was examined. EPCs were measured as CD34(+) CD133(+) CD45(low) VEGFR2(+) cells determined by flow cytometry. RESULTS The EPC numbers exhibited a strong correlation (R(2) = 0.866) with endothelial-colony forming units on culture assay. The levels of EPCs in HD or CAPD subjects were significantly lower than those in control subjects. Among ESRD subjects, the levels of EPC were significantly higher in CAPD subjects than those in HD subjects. In ESRD subjects, PWV levels tended to be associated with EPCs (Rs = -0.131, P = 0.058). However, the significant relationship between dialysis modality and circulating EPCs was independent of the levels of PWV. The association of circulating EPCs with dialysis modality was significant even after adjusting for other potential confounders, including age, gender, blood pressure, history of cardiovascular diseases, presence of diabetes, blood haemoglobin level and treatments with angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker or statin. CONCLUSIONS CAPD treatment could be a positive regulator of number of circulating EPCs in subjects with ESRD, with the relationship independent of the status of arteriosclerosis.

Active Vitamin D and Acute Respiratory Infections in Dialysis Patients

BACKGROUND AND OBJECTIVES Vitamin D has gained attention for its pleiotropic effects in areas other than bone metabolism, and the effects of vitamin D in preventing respiratory infections have been reported as one of its immunomodulating properties. This study assessed the preventive effect of vitamin D receptor activator (VDRA) on respiratory infections in dialysis patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Maintained Japanese hemodialysis patients (n = 508) were observed for 5 years, and the incidence of hospitalization during this period because of acute respiratory infection (ARI) was recorded. RESULTS Of the 508 patients, 212 had taken oral VDRA at the start of the study, whereas 296 patients had not received it. During the 5-year follow-up period, 57 patients were hospitalized because of ARIs. Kaplan-Meier analysis revealed that the incidence of hospitalization because of respiratory infection was significantly lower in patients who had been treated with VDRA compared with patients who had not (log rank test; P = 0.02). The multivariate Cox proportional hazards model demonstrated that the patients who had taken oral VDRA were at a significantly lower risk of hospitalization because of respiratory disease (hazard ratio 0.47, 95% confidence interval 0.25 to 0.90). CONCLUSIONS The findings of this study suggest that the administration of oral VDRA has a preventive effect on the incidence of ARIs in dialysis patients.

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.

Poor Glycemic Control is a Significant Predictor of Cardiovascular Events in Chronic Hemodialysis Patients With Diabetes

We investigated the impact of glycemic control on the emergence of cardiovascular disease (CVD) in diabetic patients who were on maintenance hemodialysis in a prospective observational study. One hundred and thirty‐four diabetic hemodialysis patients (63 ± 10 years‐old, hemodialysis duration of 4.5 ± 3.9 years) at a single dialysis center were enrolled. The cohort was observed prospectively for 5 years, and the emergence of fatal and non‐fatal CVD was recorded. Patients were categorized into two groups; good (mean hemoglobin (Hb) A1C <7.0%, N = 65) and poor HbA1C (mean HbA1C ≥7.0%, N = 69). The relationship between glycemic control and CVD emergence was evaluated by Kaplan‐Meier estimation and Cox proportional hazard models. During the follow‐up period, 50 CVD events were observed. The cumulative CVD incidence in the poor HbA1C group was significantly higher than that of the good HbA1C group, as determined by Kaplan‐Meier estimation (P = 0.0250, log‐rank test). After adjustment for gender, age, duration of dialysis, and past history of CVD, a multivariate Cox proportional hazard model showed that poor HbA1C was a significant predictor of CVD events (hazards ratio [HR] 1.828 [95% CI, 1.008–3.314], P = 0.0470). When ischemic heart disease, cerebral infarction, and arteriosclerosis obliterans were determined as an endpoint, both HbA1C levels and the poor HbA1C group were significant predictors for the emergence of CVD (HR 1.269 per 1% HbA1C [95%CI, 1.022–1.574], P = 0.0307,and HR 2.816 [95% CI, 1.377–5.759], P = 0.0046, respectively). In diabetic hemodialysis patients, poor glycemic control is a significant, independent predictor of the emergence of CVD, indicating the importance of careful management of glycemic control in hemodialysis patients.

Elemental Concentrations in Scalp Hair, Nutritional Status and Health-Related Quality of Life in Hemodialysis Patients

Elemental concentrations in hair from hemodialysis (HD) patients have not been well investigated. We examined the relationships between the elemental concentrations in scalp hair and health‐related quality of life (HRQOL) and nutritional status in HD patients. Twenty six elemental concentrations were measured in scalp hair samples from 60 male HD patients using inductively‐coupled plasma mass spectrometry. To evaluate HRQOL, the Short Form 36 item health survey (SF36) was used. As indices of nutritional status, body mass index, serum parameters, and geriatric nutritional risk index (GNRI) were used. Phosphorus correlated positively with serum creatinine, blood urea nitrogen (BUN), GNRI and the physical domains of the SF36. Zinc correlated positively with serum creatinine, BUN and the physical domains of the SF36. Mercury and arsenic correlated positively with BUN. Cadmium correlated negatively with serum albumin, BUN and GNRI. Copper correlated positively with the physical domains of the SF36. Iodine correlated negatively with the physical domains of the SF36. Selenium correlated negatively with the mental domains of the SF36. In conclusion, phosphorus and zinc concentrations in scalp hair can be additional biomarkers of HRQOL and/or nutritional status in HD patients. Cadmium accumulation correlated with malnutrition. Iodine and selenium accumulation may adversely affect HRQOL. Further investigation is necessary to determine precisely how these elements affect these measures.