Association of serum total testosterone concentration with skeletal muscle mass in men under hemodialysis.

PURPOSE: Although skeletal muscle wasting can occur in chronic kidney diseases, its relationship with the serum testosterone concentration remains uncertain. This study investigates the relationship between serum testosterone and skeletal muscle mass in men under hemodialysis (HD). METHODS: Sixty men aged between 41 and 89 years undergoing HD for 15.0 ± 8.1 years were enrolled for this study. The muscle areas of the thigh (TMA) and abdomen (AMA) were measured by computed tomography (CT), and the association between these muscle areas and serum total testosterone was examined with adjustment of age and other nutritional variables. RESULTS: The mean serum total testosterone in our HD patients (6.33 ± 2.90 ng/mL) was not lower than that of the Japanese general population, but showed a positive correlation with TMA (r = 0.39, p < 0.05), AMA (r = 0.52, p < 0.001), serum creatinine (r = 0.33, p < 0.05), and the creatinine generation rate (r = 0.26, p < 0.05). Serum total testosterone was inversely correlated with age (r = -0.32, p < 0.05), CRP (r = -0.31, p < 0.05), and IL-6 (r = -0.24, p < 0.05). A multiple-regression analysis showed both serum total testosterone and age to be an independent determinant of the muscle mass in these patients. CONCLUSIONS: This study identified testosterone as a determinant of muscle mass in HD men.

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.

Association of HCV core antigen seropositivity with long-term mortality in patients on regular hemodialysis.

Anti-hepatitis C virus (HCV) antibody seropositivity is independently associated with poor prognosis in hemodialysis (HD) patients. However, anti-HCV antibody cannot distinguish between patients with active infection and those who have recovered from infection. We therefore aimed in this study to examine the association of HCV core antigen (HCVcAg) seropositivity with mortality in HD patients. We first measured serum HCVcAg using an immunoradiometric assay and anti-HCV antibody in 405 patients on regular HD, and followed them for 104 months. There were 82 patients (20.2%) who had been positive for anti-HCV antibodies; 57 (69.5%) of these were positive for HCVcAg. During the follow-up, 29 patients were excluded, so we tested the association of HCVcAg seropositivity with all-cause, cardiovascular (CV) and non-CV mortalities in 376 patients. A total of 209 patients (55.6%) had expired during the observational period, 92 out of them due to CV causes. After adjusting for comorbid parameters, HCVcAg was independently associated with overall mortality (HR 1.61, 95% CI 1.05-2.47, p < 0.05). HCV infection was significantly related to liver disease-related mortality. Past HCV infection also contributed to CV mortality (HR 2.63, 95% CI 1.27-5.45, p < 0.01). In contrast, anti-HCV antibody and HCVcAg seropositivities did not associate with infectious disease-related and cancer-related (expect for hepatocellular carcinoma) mortality. It follows from these findings that HCVcAg serology is associated with all-cause and CV mortality in HD patients.

Simplified nutritional screening tools for patients on maintenance hemodialysis.

BACKGROUND: Malnutrition is a prevalent complication in patients on maintenance hemodialysis. Nutritional screening tools may be useful to identify those patients at nutritional risk from among hundreds of hemodialysis patients in a large facility. OBJECTIVE: We tested several simplified nutritional screening tools on hemodialysis patients to validate the potential application of the tools. DESIGN: The simplified nutritional screening tools were chosen from references published between 1985 and 2005. Nutritional assessments, including history taking, and anthropometric and biochemical measurements were performed on 422 hemodialysis patients. These results were applied to obtain the score of each nutritional screening tool and the malnutrition-inflammation score (MIS), a comprehensive nutritional assessment tool, as the reference standard. The usefulness of each nutritional screening tool for identifying nutritional risk was assessed by comparison with the MIS value and various individual nutritional measures. RESULTS: Five reliable nutritional screening tools were found by the literature search. Among them, the geriatric nutritional risk index (GNRI) was considered to be the most accurate in identifying hemodialysis patients at nutritional risk, because the area under the receiver operating characteristic curve generated with the MIS value was the largest. The GNRI showed a significantly negative correlation with the MIS (r=-0.67, P<0.0001), and the most accurate GNRI cutoff to identify a malnourished patient according to the MIS was <91.2. The GNRI's sensitivity, specificity, and accuracy of <91.2 in predicting malnutrition according to the MIS were 0.730, 0.819, and 0.787, respectively. CONCLUSION: The GNRI was the simplest and most accurate risk index for identifying hemodialysis patients at nutritional risk according to the MIS.

Association between seroprevalence of anti-chlamydial antibodies and long-term cardiovascular mortality in chronic hemodialysis patients.

Chlamydial infection has been suspected in the pathogenesis of ischemic heart disease. However, it remains undetermined if persistent chlamydial infection is related to cardiovascular mortality in regular hemodialysis (HD) patients. We measured Chlamydia pneumoniae (Cp) antibody seropositivity in 154 HD subjects (age 59 +/- 11 years, time on HD 13 +/- 7 years, male/female = 101/53), and prospectively examined an association between Cp antibody status and cardiovascular death for 56 months of follow-up. Seropositivity for Cp IgA and IgG antibodies at the entry of the study was 50.6 and 60.8%, respectively. There was no significant difference in age, time on HD, serum albumin, C-reactive protein (CRP) and interleukin-6 (IL-6) between those positive and negative for IgA antibodies. During follow-up over 56 months, 31 patients (20.1%) expired, 16 (55.2%) of them of cardiovascular causes. Serological IgA and IgG antibody positivity did not influence mortality, while multiple Cox proportional hazards analysis revealed that diabetes, ischemic changes on electrocardiogram, log-transformed CRP and intact parathyroid hormone were independent determinants of cardiovascular death. These observations suggest that serological Cp antibody status does not affect long-term cardiovascular mortality in chronic HD patients.

Chlamydial infection and progression of carotid atherosclerosis in patients on regular haemodialysis.

BACKGROUND: Recent findings have suggested a possible contribution of chlamydial infection to the pathogenesis of atherosclerosis in the general population. However, the role that chlamydial antibody status plays in atherosclerosis generation in haemodialysis (HD) patients remains uncertain. METHODS: We measured carotid artery intima medial thickness (IMT) over 4 years in 100 HD subjects (age: 58+/-10 years; time on HD: 13+/-7 years; male/female: 67/33) and examined potential associations between Chlamydia pneumoniae (Cp) antibody seropositivity and changes in carotid artery IMT. RESULTS: During 4 years, carotid artery IMT increased significantly from 0.62+/-0.13 to 0.73+/-0.12 mm (P< 0.01). IMT progression was significantly and positively correlated with age (r = 0.37, P<0.01), log-transformed C-reactive protein (CRP; r = 0.33, P<0.01) and log-transformed interleukin-6 (IL-6; r = 0.22, P<0.04), but inversely correlated with blood creatinine (r = -0.36, P<0.01) and albumin (r = -0.24, P<0.02). IMT increases were more prominent in patients positive for IgA antibodies (0.039+/- 0.022 mm/year, n = 52) compared with those without IgA antibodies (0.025+/-0.032 mm/year, n = 48) (P<0.01). IgA seropositivity did not accelerate IMT progression in patients with increased CRP (>0.11 mg/dl, n = 53), but significantly increased IMT to a greater extent in IgA-positive subjects than in IgA-negative subjects having lower CRP (

Role of soluble receptors for tumor necrosis factor alpha in the development of hypoalbuminemia in hemodialysis patients.

BACKGROUND: Hypoalbuminemia is a significant predictor of mortality in patients on hemodialysis (HD). The cause of hypoalbuminemia in HD patients, however, remains to be clarified. Recent studies have demonstrated that high blood concentrations of soluble receptors for tumor necrosis factor (sTNFRs) are associated with malnutrition in a variety of diseases and that the blood sTNFRs concentrations are elevated in HD patients. METHODS: The serum concentrations of tumor necrosis factor alpha, sTNFR (p55 and p80), and interleukin (IL) 6 were measured in 21 HD patients with low (equal to or less than 3.6 g/dl) and in 19 HD patients with normal (equal to or more than 4.0 g/dl) concentrations of serum albumin who were free from acute infection, malignancy, collagen diseases, liver diseases, or surgery. The correlation between these parameters and the degree of hypoalbuminemia was examined. RESULTS: The serum concentrations of sTNFR p80 and IL-6 were significantly higher in patients with hypoalbuminemia as compared with those with normoalbuminemia (sTNFR p80: 47.4 +/- 4.7 vs. 35.3 +/- 2.1 ng/ml, p < 0.05; IL-6: 10.8 +/- 2.0 vs. 6.3 +/- 0.5 pg/ml, p < 0.05). In contrast, there was no difference in the serum concentrations of tumor necrosis factor alpha and sTNFR p55 between the two groups. Multivariate regression analysis showed that sTNFR p80 but not IL-6 significantly influenced the serum albumin concentrations. There were no significant differences in body mass index, serum total cholesterol, and normalized protein catabolic rate between the two groups. CONCLUSIONS: Our results suggest the development of hypoalbuminemia in some HD patients who do not have any obvious cause of hypoalbuminemia and that high concentrations of sTNFR p80 might contribute to the development of hypoalbuminemia in patients on long-term HD.

Association between interleukin-6 and carotid atherosclerosis in hemodialysis patients.

BACKGROUND: Interleukin-6 (IL-6) is associated with cardiovascular complications in general subjects. Although blood IL-6 is greatly elevated in hemodialysis (HD) patients, the role of IL-6 in the advance of atherosclerosis remains to be determined. METHODS: We conducted a cross-sectional study to investigate the relationship between circulating IL-6 and carotid atherosclerotic changes in 156 HD patients (age 58 +/- 1 years; time on HD treatment 13 +/- 1 years; 97 males and 59 females). Serum IL-6, IgG and IgA titers of Chlamydia pneumoniae antibodies, the intima-media thickness (IMT) and the cross-sectional intima-media area (IMarea) of the carotid arteries were measured by ultrasonography in each patient. RESULTS: Serum IL-6 levels were significantly higher in HD patients (2.04 +/- 0.16 pg/mL) compared to normal age-matched control subjects (0.31 +/- 0.06 pg/mL, N = 24). Circulating log IL-6 levels were positively correlated with IMT (r = 0.278, P < 0.01) and IMarea (r = 0.344, P < 0.01), respectively. A stepwise multiple regression analysis revealed that IL-6 became significant predictors for IMT and IMarea but not for aortic wall calcification at L2/3 vertebrae. Serum log IL-6 was significantly correlated with IgG (r = 0.277, P < 0.01) and IgA titers of anti-Chlamydia antibodies (r = 0.192, P < 0.02). Serum IgA anti-Chlamydia titers were also correlated with the maximal diameter of carotid plaque (r = 0.293, P < 0.04). CONCLUSIONS: These findings suggested that IL-6 is associated with the severity of carotid atherosclerosis in HD patients. Persistent chronic chlamydial infection may be related, in part, to the advance of carotid plaque enlargement in dialysis patients.