Luigi Tazza

Circulating Bacterial-Derived DNA Fragments and Markers of Inflammation in Chronic Hemodialysis Patients

BACKGROUND AND OBJECTIVES Bacterial-derived DNA fragments (BDNAs) have been shown to be present in dialysis fluid, to pass through dialyzer membranes, and to induce IL-6 (IL-6) in mononuclear cells. The present study aimed at assessing the eventual presence of BDNAs in the blood of hemodialysis (HD) patients and if this is associated with markers of chronic inflammation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fifty-eight HD patients and 30 controls were included in the study. A blood sample was collected from a peripheral vein and from the central venous catheter (CVC) or the arteriovenous fistula (AVF) and examined for presence of BDNAs by 16S rRNA gene PCR amplification, bacterial growth, and measurement of C-reactive protein and IL-6. Thirty minutes after the start of HD, a sample of dialysis fluid was collected before the entry into and at the exit of the dialyzer and examined for presence of BDNAs. RESULTS Controls had negative blood cultures and absence of blood BDNAs. All HD patients had negative blood cultures, but in 12 (20.7%), BDNAs were present in the whole blood. In five of the latter, BDNAs were also found in the dialysis fluid. C-reactive protein serum levels (mg/L) were significantly higher in patients with than in those without BDNAs. Likewise, IL-6 serum levels (pg/ml) were significantly higher in patients with BDNA than in those without. CONCLUSIONS Circulating BDNAs are associated with higher levels of C-reactive protein and IL-6 in HD patients.

Anorexia and Serum Leptin Levels in Hemodialysis Patients

Background and Aims: Hyperleptinemia is a common feature in hemodialysis (HD) patients. However, the role of increased serum leptin levels in the pathogenesis of HD-related anorexia is still controversial. The purpose of the present prospective study was to ascertain whether hyperleptinemia is causally implicated in the pathogenesis of HD-related anorexia. Methods: We measured the serum leptin levels and the serum leptin/body mass index (BMI) ratio in 24 healthy subjects and in 49 end-stage renal disease patients on maintenance HD. HD patients were subdivided into anorexic (14/49, 28.5%) and non-anorexic (35/49, 71.5%) according to a questionnaire discriminating for the presence of anorexia-related symptoms. Results: Calorie (kcal/kg/day) and protein (g/ kg/day) intakes were significantly lower in anorexic than in non-anorexic patients (20.1 ± 1.1 vs. 27.9 ± 1.3, p = 0.004, and 0.82 ± 0.05 vs. 1.19 ± 0.05, p = 0.001, respectively). Accordingly, serum albumin, total lymphocyte count, mid-arm muscle circumference, and the protein equivalence of nitrogen appearance (PNA) were significantly lower in anorexic patients. The serum leptin concentration (ng/ml) was significantly higher in HD patients than in controls, in males (15.33 ± 3.4 vs. 3.7 ± 0.3, p = 0.003) and in females (42.3 ± 7.2 vs. 10.5 ± 1.3, p = 0.03). Similarly, serum leptin/BMI ratio was significantly higher in HD patients than in controls, in males (0.56 ± 0.1 vs. 0.16 ± 0.02, p = 0.0028) and in females (1.8 ± 0.2 vs. 0.4 ± 0.04, p < 0.0001). However, serum leptin levels were similar in anorexic and in non-anorexic patients, in males (15.3 ± 5.6 vs. 16.9 ± 4.2, p = 0.85) and in females (46.6 ± 12.9 vs. 47.4 ± 9.4, p = 0.96). No differences were observed between the 2 groups in the serum leptin/BMI ratio, in males (0.59 ± 0.2 vs. 0.58 ± 0.14, p = 0.92) and in females (1.5 ± 0.4 vs. 1.8 ± 0.3, p = 0.94). Similarly, no statistically significant differences in terms of serum leptin levels and leptin/BMI ratio were observed between patients with dietary energy intake of <30 or ≧30 kcal/kg/day and between those with a dietary protein intake of <1.2 or ≧1.2 g/kg/day. No significant correlations were found between serum leptin levels and PNA, albumin, cholesterol, total lymphocytes number, weight change, C-reactive protein, fibrinogen, ferritin, and complement. Conclusion: The present results indicate that mechanisms other than increases in serum leptin levels might be involved in the pathogenesis of HD-related anorexia.

Correlates of symptoms of depression and anxiety in chronic hemodialysis patients

OBJECTIVE Little is known about the demographic, clinical and laboratory variables which may be correlated with symptoms of depression and anxiety in hemodialysis (HD) patients. The present study aimed at evaluating such correlation in HD patients treated at a single HD center in a Mediterranean country. METHODS Eighty HD patients were assessed for depression and anxiety with the Beck Depression Inventory (BDI) and the Hamilton Anxiety Rating Scale (HARS). The scores of BDI and HARS were correlated with demographic, clinical and laboratory variables. RESULTS Based on the Beck Depression Inventory, 38 patients had no symptoms of depression and 42 had symptoms of depression. Based on the HARS, three patients had no symptoms of anxiety and 38 had mild symptoms of anxiety, whereas moderate or severe symptoms of anxiety were present in 39 patients. In univariate analysis, BDI score correlated significantly with age, the Charlson Comorbidity Index, SF-36 Vitality Subscale, Mini-Mental Status Examination, creatinine, albumin, plasma 25-hydroxy vitamin D and interleukin-6 (IL-6) levels. HARS score correlated significantly with age, Charlson Comorbidity Index, SF-36 Vitality Subscale and parathyroid hormone (PTH) levels. In the multivariate analysis, a direct and an inverse correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01-1.71)] and creatinine [P=.050, OR=0.73 (95% CI=0.54-1.00)] was observed. With regard to HARS, only a direct correlation with Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)] was found. CONCLUSION Although numerous demographic, clinical and laboratory variables correlated with BDI and HARS in univariate analysis, the multivariate regression analysis showed only a direct correlation between BDI and IL-6 [P=.042, OR=1.31 (95% CI=1.01-1.71)] and an inverse correlation between BDI and creatinine [P=.050, OR=0.73 (95% CI=0.54-1.00)] and a direct correlation between HARS and the Charlson Comorbidity Index [P<.001, OR=1.55 (95% CI=1.22-1.96)].

Antioxidant status and dialysis: Plasma and saliva antioxidant activity in patients with fluctuating urate levels

The present study is concerned with the influence of processes occurring during dialysis on the antioxidant capacity of plasma and saliva. The biological fluids were also tested for uric acid and total protein content. Before hemodialysis, plasma antioxidant status of hemodialyzed patients appears slightly higher than the corresponding status in normal subjects; after hemodialysis it is found unchanged. The result can be explained by a balance between a reduction in uric acid plasma content, due to the dialytic procedure, and an increase in protein content, possibly due to a dialysis-related hemoconcentration. Moreover, pre-dialysis total antioxidant capacity of whole saliva samples is higher than in healthy individuals and drastically decreases towards normal values following dialytic procedure. Our data indicate a certain concentration of the uric acid in the saliva of hemodialyzed patients and evidence that both total protein concentration and uric acid level show a good correlation with saliva total antioxidant capacity, suggesting that proteins are major antioxidants of this fluid. Further observations are needed to assess whether this improved saliva antioxidant ability has any consequence on the periodontal conditions of hemodialyzed subjects.

Fatigue in Chronic Dialysis Patients

Fatigue is common in chronic hemodialysis (HD) patients and impacts on daily living, impairs significantly the quality of life, increases the risk of cardiovascular events and negatively influences survival. Although numerous social, demographic, clinical, and laboratory variables have been associated with fatigue, the causes of this symptom are often unclear. In the absence of an underlying, treatable disorder, the results of therapeutic intervention are typically frustrating. So far, none of the drugs tested can be recommended for preventing and treating fatigue in chronic HD patients. There is some evidence that exercise may significantly improve fatigue in dialysis patients; however, this requires confirmation through large, prospective, randomized studies.

Is there any survival advantage of obesity in Southern European haemodialysis patients

BACKGROUND In the general population, a high body mass index (BMI) is associated with increased cardiovascular disease and all-cause mortality. However, according to US epidemiological evaluation in maintenance haemodialysis (HD) patients, a reverse epidemiology is described and baseline obesity appears paradoxically associated with better survival. The aim of this study is to examine in a Southern European HD population the relationship between survival and BMI at the start of HD treatment, and how survival is influenced by the body weight (BW) variations during the first year of treatment. METHODS A total of 85 dialysis centres located in Portugal, France and Italy and belonging to the FME European dialysis chain were included. The current prospective analysis focuses on incident patients admitted to these centres between 1 January 2000 and 30 September 2005 with <1 month of previous follow-up on RRT. Data were gained from the FME EuCliD database. Patients were classified at baseline in four categories according to the BMI: underweight, normal range, overweight and obese. Also, the patient survival was analysed according to five quintiles of BW changes during the first year of HD treatment <-5.8%, -5.8 to -1.1%, -1.1 to 1.7% (reference category), +1.7 to +5.5% and >+5.5%. Survival analysis was adjusted for a set of demographic and comorbids using Kaplan-Meier curves and Cox model. Hazard ratios and their 95% confidence intervals were calculated with the use of the estimated regression coefficients and their standard errors. RESULTS A total of 5592 patients were analysed (40.9% females), and the mean age at admission was 64.4 + 16.5 years. Of them, 27.7% were diabetic. The mean follow-up was 2.0 +/- 1.6 years. Almost half of the patients (46.4%) were in the normal range of BMI (20-24.9 kg/m(2)). When analysed with the Cox model, the categories of baseline BMI (underweight, normal range, overweight and obese) significantly influenced the survival with the respective hazard ratio (HR) and confidence interval at 1.14 (0.96-1.35), 1, 0.74 (0.67-0.9) and 0.78 (0.56-0.87). The strength of the association as well as the shape of the curve remains unchanged after considering age, diabetes and comorbidities. Moreover, when compared to patients for whom BW remained stable during the first year of HD treatment, survival was significantly lower in patients presenting in the lower quintile of BW variation (<-5.8% in 1 year) with an HR of 1.6. CONCLUSIONS Despite increased comorbidities, overweight and obese patients on maintenance HD carry a significant lower mortality risk than patients in the normal and lower BMI ranges. This confirms the reverse epidemiology previously reported in US HD patients for these categories of BMI. Also BW variation during the first year of HD treatment is associated with patient survival, highlighting the importance of nutrition in this setting.

Destructive spondyloarthropathy of the cervical spine in long-term hemodialyzed patients: a five-year clinical radiological prospective study.

Abstract. Objective:To describe the radiographic features and progression of cervical spine destructive spondyloarthropathy (DSA) in hemodialyzed patients, and to evaluate the relationship between this disease and patient characteristics, biochemical values, and hemodialysis duration. Design and patients:Standard radiographs, and lateral flexion and extension views of the cervical spine, were performed annually for 5 years in 31 hemodialyzed patients who were divided into three groups at the commencement of the study: those showing (I) DSA, (II) vertebral rim erosions (VRE) without DSA, and (III) absence of DSA and VRE. Magnetic resonance (MR) imaging and computed tomography (CT) were performed in seven and two patients respectively. The imaging features were evaluated for the presence and progression of spondyloarthropathy and correlated with clinical and biochemical variables. Statistical analysis was performed using one-way analysis of variance. Results: The duration of hemodialysis appeared to be the main predictive factor (P=0.0003) for DSA, which was found in six patients (19%). DSA was found to correlate with higher levels of beta2-microglobulin (P<0.00001), parathyroid hormone (P<0.05), and alkaline phosphatase (P<0.05). Clinical symptoms were minimal. In two patients, MR imaging revealed changes mimicking spondylodiscitis. In another patient, CT of the craniocervical junction showed bone resorption due to a pseudotumor, and basilar invagination. Conclusions: DSA of the cervical spine is often clinically silent. Pathogenesis of DSA may be multifactorial but its progression is most influenced by the duration of hemodialysis. On MR imaging, DSA may mimic spondylodiscitis.

Mechanisms and Treatment of Anorexia in End-Stage Renal Disease Patients on Hemodialysis

Anorexia, defined as the loss of the desire to eat, is relatively common in hemodialysis patients, occurring in one third of such cases. The pathogenesis is essentially unknown. It has been proposed that uremic toxins such as middle molecules, inflammation, altered amino acid pattern, leptin, ghrelin, and neuropeptide Y are involved. Anorexia reduces oral energy and protein intakes, thus contributing to the development of malnutrition and cachexia. Unquestionably, it contributes to poor quality of life. The clinical relevance of anorexia as an independent prognostic factor in hemodialysis is debated. The treatment of this debilitating condition is based on a therapeutic strategy that may include daily dialysis sessions and nutritional counseling. Normalization of plasma branched chain amino acids through branched chain amino acid supplementation may decrease anorexia and improve energy and protein intake. The role of megestrol acetate as an appetite stimulant needs to be validated through adequate randomized trials. Subcutaneous ghrelin administration and melanocortin-receptor antagonists appear to be promising therapeutic interventions.

Fatigue and Its Correlates in Chronic Hemodialysis Patients

Background: The present study aimed at evaluating the possible correlation between fatigue and demographic, clinical and laboratory variables in chronic HD patients. Methods: Sixty-two chronic HD patients were assessed for the presence of fatigue through the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), and the Mini-Mental State Examination. In all, the number/severity of comorbidities was assessed through the Charlson Comorbidity Index and laboratory parameters were measured. Results: Correlations among the SF-36 Vitality subscale and age, dialytic age, BDI, HARS and the Charlson Comorbidity Index were statistically significant. Correlations between the SF-36 vitality score and the serum creatinine, albumin and IL-6 levels were also significant. Twenty-six and 36 patients constituted the fatigued and nonfatigued groups, respectively. The age and the scores of the Charlson Comorbidity Index, BDI and HARS of fatigued patients were significantly higher than those of nonfatigued subjects. Serum IL-6 levels were significantly higher in the fatigued than in the nonfatigued group, whereas serum albumin and creatinine levels were significantly lower. Conclusions: We found that depression, anxiety, number and severity of comorbidities and IL-6 levels are significantly correlated with fatigue in end-stage renal disease patients receiving chronic hemodialysis.

Fatigue Is Associated With Serum Interleukin-6 Levels and Symptoms of Depression in Patients on Chronic Hemodialysis

CONTEXT Little is known about activated immune-inflammatory pathways and interleukin-6 (IL-6) in the development of fatigue and/or depression in patients with end-stage renal disease on chronic hemodialysis (HD). OBJECTIVES To evaluate the possible correlation between fatigue and serum levels of IL-6 in patients on chronic HD. METHODS One hundred HD patients were assessed for the presence of fatigue using the SF-36 Vitality subscale and were administered the Beck Depression Inventory (BDI), the Hamilton Anxiety Rating Scale (HARS), the Mini-Mental State Examination (MMSE), the activities of daily living (ADL), and the instrumental activities of daily living (IADL). We also calculated the time of recovery after hemodialysis (TIRD) and the number/severity of comorbidities using the Charlson Comorbidity Index (CCI). Laboratory parameters were measured as well as serum IL-6. RESULTS Forty-three patients constituted the fatigued group and 57 the nonfatigued group. Age, CCI, BDI, HARS, and TIRD were significantly higher in fatigued patients than in the nonfatigued patients. Conversely, the scores of ADL, IADL, and MMSE were significantly lower in fatigued than in nonfatigued patients. Serum IL-6 levels (pg/mL) were higher in the fatigued group (5.1 ± 3.4) than in the nonfatigued group (1.6 ± 1.5; P < 0.001); serum albumin and creatinine levels were significantly lower. Twenty-six patients (26%) had no symptoms of depression (BDI score <10), and 74 patients (74%) had symptoms of depression (BDI score >9). Patients with a BDI score >9 were older; had a higher CCI; a lower MMSE; a higher TIRD; lower serum albumin, creatinine, and urea levels; and higher serum IL-6 levels. The correlation analyses showed that the score of the SF-36 Vitality subscale was associated with age, dialytic age, TIRD, ADL, IADL, CCI, BDI, HARS, MMSE, serum urea, creatinine, albumin, and IL-6 levels. On multivariate general linear model analyses, with fatigue as the dependent variable and gender as a second factor, BDI and serum IL-6 levels were independently associated with the score of the SF-36 Vitality subscale. A canonical correlation analysis was performed including in the model fatigue, BDI, and biomarkers; the correlation was 0.679 (R(2) = 0.462). Fatigue, BDI, and IL-6 among biomarkers showed the strongest association with the underlying construct (standardized canonical coefficients = -0.989, 0.015, and 0.852, respectively), thus explaining a correlation of IL-6 with both depression and fatigue. CONCLUSION Fatigue was significantly associated with symptoms of depression and serum IL-6 levels in patients receiving chronic HD.