Anorexia, fatigue, and plasma interleukin-6 levels in chronic hemodialysis patients.

This study aimed at evaluating the possible relationship between anorexia and fatigue in hemodialysis (HD) patients and at measuring the plasma levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in HD patients with or without anorexia and/or fatigue. The first question of the Hemodialysis Study Appetite questionnaire was used to assess the appetite of the HD patients and the vitality scale of the SF-36 to assess fatigue. The Charlson Comorbidity Index was assessed in each patient. Seventy-six HD patients were studied. Forty-four were males and 32 females. Thirty-two were classified as not-anorexic and not-fatigued, 12 as not-anorexic but fatigued, 6 as anorexic and not-fatigued, and 26 as anorexic and fatigued. Plasma IL-6 levels (pg/mL) were significantly higher in anorexic and fatigued patients (10.9 ± 11.9) than in not-anorexic and not-fatigued (1.6 ± 0.6) (p < 0.001) and in anorexic but not-fatigued patients (1.8 ± 1.7) (p < 0.01). With respect to not-anorexic but fatigued patients (3.1 ± 1.5), the difference was not statistically significant (p = 0.058). The plasma CRP levels (mg/dL) also were significantly higher in anorexic and fatigued patients (9.2 ± 6.3) than in not-anorexic and not-fatigued patients (4.1 ± 4.5), in anorexic but not-fatigued patients (2.5 ± 1.6), and in not-anorexic but fatigued patients (4.1 ± 4.4) (p = 0.001). The presence of both anorexia and fatigue in chronic HD patients is associated with significantly higher levels of plasma IL-6 and CRP and a higher frequency of comorbidities.

Parathyroid gland ultrasound patterns and biochemical findings after one-year cinacalcet treatment for advanced secondary hyperparathyroidism.

Cinacalcet efficacy is limited in severe secondary hyperparathyroidism (SHPT) and its effect on parathyroid gland (PTG) volume and morphology have not been sufficiently investigated. We evaluated the effect of cinacalcet treatment for one year on the laboratory parameters of calcium-phosphorus metabolism and PTG ultrasound (US) patterns in hemodialysis (HD) patients with severe SHPT and US results indicative of nodular hyperplasia. Thirteen HD patients with severe SHPT (intact parathyroid hormone >700 pg/mL), US/scintigraphic evidence of at least one PTG with a diameter >7 mm, and high surgical risk or refusal of surgery were included. The patients were treated with cinacalcet. The initial dose of 30 mg was increased up to 180 mg once daily. At baseline and after one year of cinacalcet treatment a neck US was performed, providing data on 22 parathyroid glands in eight patients. The mean diameter at baseline and at one year was 12.6 +/- 5.9 and 13.0 +/- 5.3 mm, respectively (P = 0.46). Similarly, the mean volume at baseline and at one year was 513.4 +/- 416.3 and 556.8 +/- 480.8 mm(3), respectively (P = 0.18). The US structural score remained unchanged in 16 parathyroid glands and increased in 6 (P < 0.03), while the vascular score remained unchanged in 16 parathyroid glands and decreased in 6 (P = 0.25). Thus it can be concluded that cinacalcet treatment for one year in HD patients with severe SHPT is not associated with significant changes in parathyroid gland US patterns.

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.

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.

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.

Body mass index and cardiovascular risk factors and biomarkers in hemodialysis patients.

BACKGROUND: Being overweight and obesity are associated with improved survival in hemodialysis (HD) patients, based on mechanisms that are presently uncertain. We compared traditional and uremia-related cardiovascular risk factors in HD patients stratified according to their body mass index (BMI). METHODS: One hundred sixteen HD patients were stratified into 4 groups according to the BMI: underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9) and obese (> or =30). Blood samples were obtained before the HD session to measure serum albumin, high-sensitivity C-reactive protein, fibrinogen, ferritin, total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein A-I and apolipoprotein B-100, apolipoprotein B (apoB) to apolipoprotein A (apoA) ratio and Lp(a) lipoprotein. RESULTS: There were 3 underweight (excluded from the analysis), 58 normal weight, 35 overweight and 20 obese patients. Their mean age was 62.1 +/- 14.1 years. There were 68 men and 45 women. Mean dialytic age was 5.32 +/- 3.2 years. The mean BMI of the study population was 25.2 +/- 4.1. The prevalence of smoking habit was similar in the 3 groups (17.2%, 8.5% and 25%, respectively; p=0.28). The prevalence of hypertension was higher in overweight (77.1%) and obese (65%) patients than in leaner counterparts (53.4%), although the difference was not significant. Conversely, diabetes prevalence was significantly higher in overweight and obese patients (22.8% and 30%, respectively) than in normal weight patients (6.9%; p=0.02). The serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, Lp(a) lipoprotein, apolipoprotein A-I, apolipoprotein B-100, and apoA/apoB ratio were similar in the 3 BMI groups. Triglycerides levels were significantly higher in obese (221.2 +/- 132.7 mg/dL) and overweight (230.5 +/- 119.3 mg/dL) patients than in those of normal weight (154.6 +/- 78.8 mg/dL; p=0.02). Most of the uremia-related cardiovascular risk factors (anemia, hyperparathyroidism, chronic inflammation) were comparable among BMI categories as well as the levels of C-reactive protein, fibrinogen and ferritin. CONCLUSION: The present study suggests that almost all traditional and uremia-related cardiovascular risk factors do not differ significantly among different categories of BMI in hemodialysis patients.

Reticulocyte hemoglobin equivalent: an indicator of reduced iron availability in chronic kidney diseases during erythropoietin therapy.

Anemia is a common complication of chronic kidney disease (CKD), particularly in dialysis patients. Correction of anemia in CKD patients includes the administration of both recombinant human erythropoietin and intravenous iron. An optimization of iron treatment requires obtaining a target hemoglobin level and avoiding an excessive body-iron overload. The reticulocyte hemoglobin content (CHr) has been shown to be an early indicator of iron-restricted erythropoiesis. The recent European guidelines for anemia treatment in CKD assessed the value for CHr >29 pg/cell as the reticulocyte parameter to evaluate a patient's iron needs. The reticulocyte hemoglobin equivalent (RET-He), recently introduced to determine the forward scatter of fluorescence-labeled reticulocytes, seems to be a sensitive indicator of iron-deficiency anemia. This study evaluates the concordance between the CHr parameter, used as a reference, and the new RET-He in a cohort of 57 dialysis patients referred to the Nephrology Unit of our hospital. All patients received erythropoietin, and iron was administered intravenously to maintain the hemoglobin level between 10 and 12 mg/dL. A total of 285 determinations were performed with both instruments. In the dialysis population, the 95% central range for CHr of 24.8 to 36.3 pg corresponds to a range for RET-He of 23.3 to 40.1 pg, with a mean bias of 1.12 pg between the 2 parameters. In comparison with CHr, the value of 30.5 pg for RET-He appeared to be the best cut-off point with a very good sensitivity and specificity to determine patients needing iron supplementation. Our study showed an excellent diagnostic efficiency of RET-He to evaluate patients needing iron support and demonstrated a strict correspondence between the classic CHr and the new Ret-He. This correspondence was independent of clinical changes, frequently occurring in dialysis patients. Both parameters could be used soon to guide and monitor iron treatment in dialysis patients.

Different profiles of patients who require dialysis after cardiac surgery.

BACKGROUND: This study was aimed at evaluating the determinants of postoperative dialysis-requiring acute renal failure and at identifying eventual correlations between the different etiologic mechanisms and postoperative prognosis. METHODS: We evaluated the preoperative and intraoperative features of the 69 out of 6,542 consecutive cardiac surgery patients who developed postoperative dialysis-requiring acute renal failure at our Institution during a 10-year period. RESULTS: Age, valvular and aortic surgery, hypertension, extracardiac vasculopathy, timing of surgery, cardiopulmonary bypass time, and preoperative creatinine level greater than 2.0 mg/dL were identified as predictors by multivariate analysis. In a second analysis, patients were divided in two groups according to the preoperative creatinine level: group A (preoperative creatinine 2.0 mg/dL or less; 38 cases) and group B (preoperative creatinine 2.1 mg/dL or more; 31 cases). The two groups significantly differed in preoperative and intraoperative characteristics and in postoperative outcome: group A patients were younger, had a lower incidence of cardiac and vascular risk factors and comorbidities, were mainly operated on urgent or emergent basis for valvular or aortic pathologies, had longer cardiopulmonary bypass and cross-clamp time, and worse in-hospital outcome but higher midterm survival. Group B patients were older, had a higher prevalence of comorbidities, required more often in-hospital or after-discharge dialysis, had lower in-hospital mortality, but reduced midterm survival. CONCLUSIONS: Postoperative dialysis-requiring acute renal failure can be the result of two different pathophysiological pathways: complicated perioperative course due to urgent-emergent surgery or main intraoperative technical complications in patients with preoperative normal renal function and uncomplicated perioperative course associated with reduced preoperative kidney function. The two patient groups significantly differ in baseline preoperative features, as well as in in-hospital and in midterm outcome.

Parathyroid carcinoma in a chronic hemodialysis patient: case report and review of the literature.

Parathyroid carcinoma is a rare disease in normal population as well as in patients with end-stage renal disease. Approximately 700 cases have been reported and, of these, 20 occurred in patients receiving chronic hemodialysis. We describe a case of parathyroid carcinoma in a 59-year-old female patient with end-stage renal disease secondary to membranous glomerulonephritis treated by hemodialysis since 1995. In September 1998, the calcium level was 12.4 mg/dl and intact parathyroid hormone serum levels were 1366 pg/ml (normal range, 25-65). A routine ultrasonographic examination of the neck revealed enlargement of two parathyroid glands, the left inferior gland being the largest and measuring 2x3x2 cm. In October 1998, resection of two parathyroid glands was performed. On the basis of histology, which documented the presence of proliferating cells arranged in sheets or in a trabecular pattern, numerous mitosis and vascular invasion, a diagnosis of parathyroid carcinoma was made.

Risks of using internal thoracic artery grafts in patients in chronic hemodialysis via upper extremity arteriovenous fistula.

BACKGROUND: In patients in chronic hemodialysis via upper extremity arteriovenous fistula in whom ipsilateral internal thoracic artery graft was used for myocardial revascularization, hemodynamic interference between the fistula and the graft during dialysis can be hypothesized. METHODS AND RESULTS: In 5 patients undergoing chronic hemodialysis via upper extremity arteriovenous fistula, ipsilateral to an internal thoracic to left anterior descending graft mammary flow was studied by means of transthoracic echo-color Doppler at baseline and during hemodialysis. Flow in the contralateral mammary artery was used as control. Transthoracic echocardiography was performed in concomitance with flow evaluation to assess eventual modifications of left ventricular segmental wall motion. Immediately after hemodialysis pump start there was a marked reduction of peak systolic and end-diastolic velocities and time average mean velocity and flow in the ITA ipsilateral to the fistula, whereas no substantial hemodynamic modification was evident in the contralateral artery. Dialysis-induced reduction of ipsilateral ITA flow was accompanied by evidence of hypokinesia of the anterior left ventricular wall. Three cases also experienced clinical angina. CONCLUSIONS: Hemodynamically evident flow steal and consequent myocardial ischemia develop during hemodialysis in patients with upper extremity arteriovenous fistula and ipsilateral internal thoracic artery to coronary graft. These data have major implications for patients' management, both for nephrologists and cardiac surgeons.

Muscle ubiquitin m-rNA levels in patients with end-stage renal disease on maintenance hemodialysis.

BACKGROUND: Loss of lean body mass is frequently reported in patients with end-stage renal disease (ES-RD). Inadequate nutrient intake, superimposed illnesses, endocrine disorders, uremia and acidosis are some of the potential causes of muscle depletion. Previous reports on experimental models show that lean body mass depletion results from enhancement of muscle tissue protein catabolism, mainly associated with activation of ATP-ubiquitin-dependent proteolysis. Little is known, however, about the affects on this proteolytic system in ESRD patients on maintenance hemodialysis (HD). The present study was designed to investigate the expression of ubiquitin mRNAs in skeletal muscle of patients with ESRD on maintenance HD. METHODS: Biopsies from the rectus abdominis muscle were obtained from eight ESRD patients and from six control subjects undergoing surgery for benign disease. Ubiquitin mRNA levels were measured by Northern blotting analysis. RESULTS: Patients with ESRD had mild metabolic acidosis, as a result of chronic intermittent HD. There were no significant differences between HD patients and controls with regard to the 1.2kb polyubiquitin mRNA species (332.9+/-139 vs 324.2+/-60; ns), but the levels of the 2.4 kb mRNA species were significantly lower in HD patients than in controls (1687+/-542 vs 2529.9+/-325, p=0.01). No correlation was observed between ubiquitin mRNA levels and nutritional parameters and degree of acidosis. CONCLUSIONS: The present study found that the ubiquitin mRNA levels were not increased in the muscle of stable, mildly acidotic hemodialysis patients.