System In Hemodialysis Patients Research Articles

Nine Months of Hybrid Intradialytic Exercise Training Improves Ejection Fraction and Cardiac Autonomic Nervous System Activity.

Cardiovascular disease is the most common cause of death in hemodialysis (HD) patients. Intradialytic aerobic exercise training has a beneficial effect on cardiovascular system function and reduces mortality in HD patients. However, the impact of other forms of exercise on the cardiovascular system, such as hybrid exercise, is not clear. Briefly, hybrid exercise combines aerobic and strength training in the same session. The present study examined whether hybrid intradialytic exercise has long-term benefits on left ventricular function and structure and the autonomous nervous system in HD patients. In this single-group design, efficacy-based intervention, twelve stable HD patients (10M/2F, 56 ± 19 years) participated in a nine-month-long hybrid intradialytic training program. Both echocardiographic assessments of left ventricular function and structure and heart rate variability (HRV) were assessed pre, during and after the end of the HD session at baseline and after the nine-month intervention. Ejection Fraction (EF), both assessed before and at the end of the HD session, appeared to be significantly improved after the intervention period compared to the baseline values (48.7 ± 11.1 vs. 58.8 ± 6.5, p = 0.046 and 50.0 ± 13.4 vs. 56.1 ± 3.4, p = 0.054 respectively). Regarding HRV assessment, hybrid exercise training increased LF and decreased HF (p < 0.05). Both conventional Doppler and tissue Doppler imaging indices of diastolic function did not change after the intervention period (p > 0.05). In conclusion, long-term intradialytic hybrid exercise training was an effective non-pharmacological approach to improving EF and the cardiac autonomous nervous system in HD patients. Such exercise training programs could be incorporated into HD units to improve the patients' cardiovascular health.

Relationship between parathyroid hormone and renin–angiotensin–aldosterone system in hemodialysis patients with secondary hyperparathyroidism

Hyperparathyroidism (HPT) is associated with mortality and cardiovascular disease (CVD) in dialysis patients. However, its mechanism is still unclear. It is suspected that parathyroid hormone (PTH) is associated with the renin-angiotensin-aldosterone system (RAAS) as a possible mechanism. Thus, we examined their hormonal interaction in hemodialysis patients with secondary HPT. Seventeen hemodialysis patients with HPT were included. All patients underwent total parathyroidectomy (PTx). Serum intact PTH (iPTH), calcium and phosphate levels, plasma renin activity (PRA), and plasma aldosterone levels (ALD) were measured pre- and post-PTx. Pre-serum iPTH tended to be correlated with pre-PRA and were significantly correlated with pre-ALD (pre-PRA: r = 0.44, p = 0.07, pre-ALD: r = 0.49, p < 0.05). With the reduction in serum iPTH after PTx, PRA and ALD significantly decreased after PTx. Additionally, the change in serum iPTH tended to be correlated with the changes in PRA and ALD (PRA; r = 0.46, p = 0.05, ALD; r = 0.45, p = 0.06). Our results suggest that PTH could be interrelated with RAAS in hemodialysis patients with secondary HPT.

Molecular Mechanisms of Premature Aging in Hemodialysis: The Complex Interplay Between Innate and Adaptive Immune Dysfunction.

Hemodialysis (HD) patient are known to be susceptible to a wide range of early and long-term complication such as chronic inflammation, infections, malnutrition, and cardiovascular disease that significantly affect the incidence of mortality. A large gap between the number of people with end-stage kidney disease (ESKD) and patients who received kidney transplantation has been identified. Therefore, there is a huge need to explore the underlying pathophysiology of HD complications in order to provide treatment guidelines. The immunological dysregulation, involving both the innate and adaptive response, plays a crucial role during the HD sessions and in chronic, maintenance treatments. Innate immune system mediators include the dysfunction of neutrophils, monocytes, and natural killer (NK) cells with signaling mediated by NOD-like receptor P3 (NLRP3) and Toll-like receptor 4 (TLR4); in addition, there is a significant activation of the complement system that is mediated by dialysis membrane-surfaces. These effectors induce a persistent, systemic, pro-inflammatory, and pro-coagulant milieu that has been described as inflammaging. The adaptive response, the imbalance in the CD4+/CD8+ T cell ratio, and the reduction of Th2 and regulatory T cells, together with an altered interaction with B lymphocyte by CD40/CD40L, have been mainly implicated in immune system dysfunction. Altogether, these observations suggest that intervention targeting the immune system in HD patients could improve morbidity and mortality. The purpose of this review is to expand our understanding on the role of immune dysfunction in both innate and adaptive response in patients undergoing hemodialysis treatment.

Antihypertensive Therapy in Patients Receiving Maintenance Hemodialysis: A Narrative Review of the Available Clinical-Trial Evidence.

Blood pressure (BP)-lowering with the use of antihypertensive drugs appears to protect the cardiovascular (CV) system in hemodialysis patients. However, the optimal treatment algorithm of hypertension remains elusive; extrapolation of clinical-trial evidence from the general population may not be optimal. For this narrative review, we searched the Medline/PubMed database (inception to August 01, 2019) to identify randomized clinical trials evaluating the efficacy of antihypertensive drugs on CV outcomes and mortality in patients on hemodialysis. Randomized trials with angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensinreceptor- blockers (ARBs) failed to provide consistent cardioprotection. β-blockers may provide a more consistent CV benefit. Although some early clinical trials have shown that mineralocorticoid-receptorantagonists (MRAs) reduce CV mortality, the associated risk of hyperkalemia raises important safety concerns on the use of MRAs as add-on therapy. Our first-line therapy of hypertension in hemodialysis is the assessment and management of dry-weight and optimization of dialysis prescription. Based on the available clinical-trial evidence, we prescribe atenolol 3 times/week after dialysis as the first-line pharmacological option of hypertension to our patients without specific indications for other agents. Long-acting dihydropyridines and ACEIs/ARBs are our second-line and third-line choices, respectively. We avoid using MRAs and await results from ongoing trials testing their safety and efficacy. In patients receiving maintenance hemodialysis, randomized trials are clearly warranted in order to define BP targets and the comparative effectiveness of different antihypertensive drugs.

Pathological damage of bones and joints in patients on hemodialysis in Saint Petersburg

BACKGROUND. The number of patients with end-stage renal disease is steadily increasing. One of the main complications arising from the disorders of calcium-phosphorus metabolism in patients on hemodialysis is various types of renal osteodystrophy. The frequency of pathological fractures among patients receiving renal replacement therapy is twice as high as in the general population. The prevalence and structure of injuries, especially the diagnosis of injuries of the musculoskeletal system in hemodialysis patients, are not well understood. THE AIM: to determine the prevalence and structure of injuries and the consequences of pathological injuries of bones and joints undergoing hemodialysis in Saint-Petersburg. To achieve this goal, the authors developed a special questionnaire, consisting of 4 blocks, including 32 questions.PATIENTS AND METHODS. An analysis of questionnaires of 798 patients from 15 hemodialysis centers of Saint-Petersburg was carried out.RESULTS. A number of problems were identified, such as insufficient coverage of patients not only with specific instrumental examination methods (MSCT, MRI), but also with radiographic ones. Satisfaction with quality of life and physical activity was noted in less than half of patients. 46.4% had a history of fractures and injuries, while the proportion of operated patients was half that, which indicates the need for more active work of hemodialysis centers with city hospitals with traumatology and orthopedic departments.CONCLUSION. Patients on HD require regular x-ray examination and densitometry to detect pathological damage to bones and joints. Based on the results of these studies, it is advisable to consult a traumatologist at least 1 time per year.

Pleiotropic effects of angiotensin II blockers in hemodialysis patients: myth or reality?

Mechanistic studies suggest that angiotensin II receptor blockers (ARBs) may have pleiotropic effects on the cardiovascular system in hemodialysis patients. A new randomized trial by Peters et al. failed to show a benefit of irbesartan on biomarkers of arterial stiffness, left ventricular mass, and autonomic nerve function. Their findings suggest that, like in the general population and other disease states, in hemodialysis patients the type of antihypertensive drug is unlikely to be of major clinical relevance.

Impact of Hyperuricemia on Cardiovascular System in ESRD Patients

Background: Hyperuricemia was found to be associated with hypertension, coronary heart disease, metabolic syndrome and chronic kidney disease. However there are no specific data about the relationship of uric acid to cardiovascular disease and mortality in ESRD patients on chronic hemodialysis. So, we aimed to study the impact of hyperuricemia on cardiovascular system in chronic kidney disease and in ESRD patients on regular hemodialysis Patients and methods: This study included 100 patients in Ashmoun hospital, nephrology department. Patients were chosen and divided into two groups: Group A, 50cases with chronic kidney disease and Group B, 50cases of ESRD on regular hemodialysis. All cases were subjected to full clinical examination, measurement of eGFR, laboratory tests for blood urea, serum creatinine and serum uric acid and ECG. Results: Serum uric acid was significantly higher in dialysis group than CKD group (p 0.05). Conclusion: In cases of CKD uric acid is involved in the pathogenesis of renal failure and hypertension. In patients with ESRD, hyperuricemia is not a risk factor for the development of cardiac disease; but it shows reversed epidemiology and becomes a marker of good nutritious status. Further studies should be done on wider scales to evaluate the impact of hyperuricemia on cardiovascular system in hemodialysis patients.

The dual blockade of the renin–angiotensin system in hemodialysis patients requires decreased dialysate sodium concentration

PurposeThe study evaluated whether the dual blockade of the renin–angiotensin system may influence the sodium balance in hemodialysis.MethodsThe study involved 148 hemodialysis patients (male 85, female 63), mean age 59.6 ± 12.9 years. Participants were randomly selected to receive either angiotensin-converting enzyme inhibitor (ACEI)—subgroup A—or dual blockade ACEI and angiotensin receptor blocker (ARB)—subgroup AA.ResultsAt baseline, in the A versus AA subgroups, the pre-dialysis sodium concentrations (mmol/l) were 137.7 ± 0.5 versus 137.9 ± 0.8, the sodium gradients 2.6 ± 0.5 versus 2.9 ± 0.4, interdialytic weight gain (IWG) (kg) 3.1 ± 0.2 versus 3.0 ± 0.3, and thirst inventory score (points) 18.1 ± 1.0 versus 19.0 ± 1.7, respectively. After 3 months of therapy, a decrease in sodium concentration to 134.5 ± 0.5 and the increase of its gradient to 5.5 ± 0.5 were noted in the AA subgroup. An elevation of mean interdialytic weight gain to 3.47 ± 0.2 and thirst score to 21.3 ± 2.1 was observed. No significant changes in subgroup A were found. One month of the dialysate sodium concentration being lowered from 140 mmol/l to 138 mmol/l was associated with reduced serum sodium concentration and gradient, decreased IWG and restored moderate thirst score in the AA subgroup (137.5 ± 0.6 and 2.9 ± 0.6, 3.0 ± 0.5 and 19.2 ± 1.3, respectively).ConclusionsThe dual blockade of the renin–angiotensin system affects sodium balance, increasing the sodium gradient, thus elevating thirst sensation and enhancing interdialytic weight gain. In maintenance hemodialysis patients treated with both ACEI and ARB, lowered dialysate sodium levels should be prescribed.

Effect of combined vitamins C and E supplementation on oxidant/antioxidant status in hemodialysis patients

The aim of this study was to evaluate the antioxidant supplementation effect on antioxidant system in hemodialysis patients. The study group consisted of 38 patients undergoing hemodialysis and 72 healthy subjects. The patients orally received combination of vitamins C (250 mg/time) and E (200 IU/time) three times per week for 2 months. Both, enzymatic antioxidants [superoxide dismutase (SOD) and glutathione peroxidase (GPx)] activities and non-enzymatic (vitamins E and C) levels and malondialdehyde (MDA) concentrations as lipid peroxidation product in patients were measured before and after supplementation compared with control group. The levels of antioxidants (vitamin E, C and SOD) (P < 0.0001) and GPx (P < 0.05) were significantly enhanced and MDA concentrations declined (P < 0.0001) during the supplementation period. The study demonstrates that combined supplementation of vitamins C and E can noticeably affect antioxidant status and protect against oxidative stress caused during hemodialysis.

The Plasma Level of Brain Natriuretic Peptide Is Increased in Malnourished Hemodialysis Patients

Background: In hemodialysis (HD) patients, the plasma brain natriuretic peptide (BNP) level is associated with left ventricular dysfunction and patients’ survival. Malnutrition is common in HD patients, it is associated with inflammation and contributes to the high incidence of cardiovascular (CV) disease in this setting (malnutrition-inflammation-atherosclerosis syndrome). In a cross-sectional study, we assessed the relationship between predialysis plasma BNP level and nutritional markers in chronic HD patients. Methods: Of 210 patients receiving HD treatment in our unit, 51 patients who were treated with three times weekly long-hour HD (5–8 h/session) for at least 6 months (mean age 65.8 ± 15.0 years; F/M ratio 23/28; vintage 71.3 ± 71.9 months; BMI 24.9 ± 5.9; session time 6.9 ± 1.3 h; percentage of diabetic patients 31%) were studied before a mid-week HD session for nutritional markers (plasma albumin 35.3 ± 3.7 g/l; prealbumin 0.36 ± 0.09 g/l; CRP 15.3 ± 14.7 mg/l; nPNA 1.29 ± 0.29 g/kg/day) and plasma BNP (246.9 ± 252.2 ng/l, normal <100 ng/l, Bayer® kit). The interdialytic weight gain was 2.1 ± 1.0 kg. In the last 3 months prior to the commencement of the study, the patients’ dry weight varied by +0.17 ± 1.9 kg. Results: Predialysis plasma BNP levels did not differ according to gender and the presence of diabetes. It was not correlated with age and vintage but was found to be negatively associated with the session time (r = –0.34, p = 0.018). Several nutritional markers were negatively correlated with BNP levels: prealbumin (r = –0.46, p = 0.001), BMI (r = –0.33, p = 0.018), nPNA (r = –0.46, p = 0.002). The plasma albumin relationship with the BNP level was close to significance (p = –0.26, p = 0.070). The 3-month dry weight variation was also negatively correlated with BNP levels (r = –0.34, p = 0.018). With multiple stepwise regression analysis, prealbumin and session time remained significant (respectively p = 0.004 and 0.01). BNP levels were higher in a subgroup of malnourished patients (n = 12) (400 ± 405 vs. 202 ± 166 ng/l, p = 0.03) than in patients who did not meet the malnutrition criteria (34 patients). They were not correlated with CRP levels, interdialytic weight gain, or predialysis MAP. Conclusions: Hence, the plasma BNP level was found to be associated with malnutrition but not with inflammation. This underlines the relationship between nutrition and the CV system in HD patients. The body weight variations associated with malnutrition and the difficulties in assessing and adjusting dry weight may lead to fluid overload, which could explain, in part, these correlations.

130: Use of Home Telemonitoring System in Hemodialysis Patients at High Risk for Volume Overload

130: Use of Home Telemonitoring System in Hemodialysis Patients at High Risk for Volume Overload

Effect of One‐year Oral α‐Tocopherol Administration on the Antioxidant Defense System in Hemodialysis Patients

Oxidative stress is increased in hemodialysis (HD) patients and contributes to the increased morbidity and mortality in this population. Vitamin E is an antioxidant agent. In the present study the effect of prolonged oral alpha-tocopherol administration on the antioxidant defense system was evaluated. The antioxidant factors plasma total antioxidant status (TAS), red blood cell superoxide dismutase (SOD) activity and glutathione peroxidase (GPX) activity were evaluated with spectrometry in 27 HD patients. Measurements were performed before and after oral administration of alpha-tocopherol at a dose of 500 mg/d for a one-year period. Twenty HD patients received a placebo and 22 healthy volunteers served as controls. TAS was increased in HD patients. No difference was detected in SOD and GPX activity between HD patients and healthy volunteers. Tocopherol administration induced a significant decrease in TAS and SOD activity. Levels of GPX activity remained unaffected. All the evaluated factors remained stable in the HD patients receiving a placebo. Prolonged oral alpha-tocopherol administration in HD patients induces a decrease in some components of the antioxidant defense system, raising the possibility for a pro-oxidative role of vitamin E. Vitamin E is an antioxidant agent, but it is also known to have pro-oxidant action under special conditions that can be encountered in HD patients.

Plasma levels of Th1/Th2 Type Cytokine are Associated with Change of Prolactin and GH/IGF-I in Hemodialysis Patients

Patients undergoing chronic hemodialysis (HD) have an impaired immune system involving both B and T cell-mediated immune responses. Since T helper type 1 (Th1) and type 2 (Th2) cytokines are implicated in regulating the immune responses, while the pituitary hormones, prolactin (PRL) and growth hormone (GH) are known to be involved in the regulation of the immune response, all of them may, therefore, be involved in impaired status. The aims of the present study were to estimate the serum concentrations of Th1-Th2 cytokine, GH, insulin-like growth factor-I (IGF-I) and PRL, and to determine whether there are any correlations between the release of T-cell cytokines and disturbance of hormones in a group of patients on maintenance hemodialysis (MHD). The study included 35 HD patients (23 males and 12 females, mean age 56.8+/-12.8 years) and a control group of 20 age-matched healthy subjects. Baseline serum concentrations of GH/IGF-I, PRL, IL-2, sIL-2R, IFN-gamma, IL-4 and IL-10 were measured in all patients and control subjects. Our results demonstrate that the fasting serum concentration of IGF-I, PRL, sIL-2R and Th1-type cytokine, including IL-2 and IFN-gamma, were significantly higher in HD patients compared to the healthy subjects. GH and Th2-type cytokine including IL-4 and IL-10 levels were slightly reduced, but no significant differences were observed between HD patients and the control group. In the group of HD patients, PRL correlated directly with IFN-gamma and correlated inversely with IL-10; IFN-gamma correlated inversely with IL-4; and GH also correlated inversely with IGF-I and IL-4. However, IGF-I correlated directly with IL-2 and IL-10. These data suggest that the Th1/Th2 imbalance in HD patients with an increase of Th1 type cytokines, associated with the altered GH/IGF-I axis and prolactin and immuno-endocrine dysfunction, probably plays a role in an impaired immune system in HD patients.

Intradialytic parenteral nutrition abolishes the increase of insulin-like growth factor binding protein-1 (IGFBP-1) during hemodialysis and elevates the IGF-I/IGFBP-1 ratio, an anticatabolic effect?

Summary Background Malnutrition is a severe clinical problem in hemodialysis (HD) patients. We have earlier shown that insulin-like growth factor binding protein-1 (IGFBP-1) increases during HD and may thus limit the bioavailability of free insulin-like growth factor-I (IGF-I). The present study was performed with the aim to test if intradialytic parenteral nutrition (IDPN) would influence the IGF system in HD patients with the hypothesis that IDPN would attenuate the increase of IGFBP-1 and thus alter the IGF system to give a more anticatabolic effect. Methods Nine HD patients aged 69±3 years were studied during one HD session with IDPN and one without IDPN. The nutritional product used contained 1000 kcal (1000 ml, 53 g amino acids, 75 g glucose and 50 g long chain triglycerides—soybean oil). Blood samples were collected pre- and post-dialysis. Serum concentrations of IGF-I, insulin and IGFBP-1 were determined by RIA. Results During HD without IDPN serum levels of IGFBP-1 increased from 84±21 to 139±26 μg/l ( p =0.01). In contrast IGFBP-1 tended to decrease from 126±37 to 85±18 μg/l ( p =0.087) during HD with IDPN. The difference between post- and pre-HD IGFBP-1 was significantly larger without IDPN than with IDPN (+55±17 vs. −41±21 μg/l, p =0.0056). The ratio IGF-I/IGFBP-1, indicative of free IGF-I, decreased significantly during HD without IDPN (4.5±1.6 vs. 2.8±1.1 p =0.02). In contrast, during IDPN this ratio tended to increase from 2.6±1.0 to 4.3±1.7 ( p =0.059). The difference between post- and pre-HD was −1.7±0.5 without IDPN vs. 1.6±0.7 μg/l with IDPN ( p =0.022). Without IDPN the change in IGF-I was non-significant during HD but on IDPN IGF-I serum levels increased significantly from 156±35 to 193±44 μg/l ( p =0.004). The serum levels of insulin differed significantly during HD with a decrease without IDPN and an increase with IDPN (−17±7 vs. +19±8 μg/l p =0.009). Glucose levels decreased without IDPN but remained unchanged with IDPN (5.9±0.9 to 4.1±0.4 mmol/l p =0.021 vs. 5.8±0.8 to 6.1±0.9 mmol/l NS). Conclusions IDPN blunts the increase of IGFBP-1 and the IGF-I/IGFBP-1 ratio increases. The increased IGF-I bioavailability suggests an anticatabolic effect.

Serum Erythropoietin Levels and Their Correlation With the Erythropoietic System in Hemodialysis Patients and Renal Allograft Recipients

Background Following renal transplantation, serum erythropoietin (EPO) levels gradually increase during the first 2 to 3 months. However, some transplant recipients continue to remain anemic. The aim of the present study was to correlate serum EPO concentrations with hematocrit (Hct) and hemoglobin (Hb) levels in hemodialysis (HD) patients and renal allograft recipients. Methods In a comparative cross-sectional study, serum EPO concentrations and Hb and Hct levels were measured in 35 chronic HD patients and 40 transplant recipients who had stable kidney function for at least 6 months after transplantation (group 1). The HD patients were further divided based on their recombinant human (rHu) EPO supplementation into those who received rHu EPO during dialysis (group 2A, n = 15) and those who were not on rHu EPO (group 2B, n = 20). Data are presented as mean values ± SD. The statistical analysis was performed by SPSS version 11.0 using chi-square, ANOVA, and Pearson correlation tests. A general linear model (GLM) was used to compensate for the effects of age. The P value for significance was set at .05. Results Group 2B patients tended to be older than groups 1 and 2A ( P = .014). The sex ratios were comparable among groups. Mean EPO level was 17.09 ± 10.99 mIU/mL in recipients, which was comparable with that of HD patients (18.54 ± 26.18 mIU/mL; P > .05). No significant correlation was observed between the serum EPO concentrations and Hb and Hct levels in recipients ( P > .05). When comparing the 3 groups, EPO was not correlated with Hct and Hb in any group. Hb and Hct were significantly higher among HD patients not on rHu EPO therapy ( P = .02). GLM, with age as a covariate, did not yield a significant difference between EPO levels of the studied groups ( P = .36). Conclusions This study showed that serum EPO level was in the normal range in recipients and HD patients. We were not able to find any correlation between Hb and Hct levels and EPO concentrations in any group of patients irrespective of rHu EPO supplementation. Hence, impaired EPO stimulatory effects may be considered a potential contributor to anemia in these patients.

Vitamin D, Cardiovascular System, and Longevity of Hemodialysis Patients

Abstract: The risk of cardiovascular death is high in hemodialysis (HD) patients, and thickening, stiffening and calcification of the arterial wall have been shown as its predictive factors. Activated vitamin D preparations are used for the treatment of secondary hyperparathyroidism in HD patients, but as they increase serum phosphate and calcium concentrations, there is a concern that they promote vascular calcification and, consequently, exacerbate the outcomes. In this article, the effects of vitamin D therapy on survival, cardiac function, arteriosclerosis, immunity, and inflammation are evaluated by reviewing the literature. In HD patients, the risk of death (particularly cardiovascular death) is significantly lower in those treated than in those not treated with vitamin D. Moreover, activated vitamin D improves cardiac function and alleviates cardiac hypertrophy in HD patients. Experimental data in cultured macrophages, vascular smooth muscle cells, and vascular endothelial cells suggest that it has antiatherosclerotic effects. In vivo, the administration of vitamin D improves immune functions and normalizes inflammatory reactions. In HD patients, vascular calcification is related to the dose of calcium carbonate, but its relationship with the administration of vitamin D is not significant. These observations suggest that, contrary to the general concerns, activated vitamin D exerts favorable effects on the cardiovascular system in HD patients as long as it is used in appropriate clinical doses.

Muscle insulin-like growth factor status, body composition, and functional capacity in hemodialysis patients.

Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients. Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-alpha (TNF-alpha) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting. Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 +/- 0.9 versus 21.5 +/- 1.5 kg, P < .05), as were all measures of functional capacity (P < .01 to .001), and highly significant positive correlations between appendicular lean mass and functional capacity were evident (appendicular lean mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test, all P < .001). TNF-alpha and TNFR1 were elevated in patients (P < .001). Although serum IGF-I and IGFBP-3 levels did not differ between the groups (P = .295 and .379 respectively), fragmented IGFBP-3 levels were increased (53.1 +/- 16.0 versus 29.81 +/- 15.3%, P < .005). In contrast, muscle IGF-I was substantially diminished in the patient group (n = 7) relative to control (n = 5) levels (0.84 +/- 0.06 versus 2.78 +/- 1.80 pg/microg, P < .05). We provide evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal factor in the muscle wasting characteristic of this population. Future research should determine the exact consequences and causes of alterations to the muscle IGF system in HD patients.

Muscle insulin-like growth factor status, body composition, and functional capacity in hemodialysis patients

<h3>Background</h3> Hemodialysis (HD) patients typically have reduced muscle mass and diminished functional capacity. The role of the muscle insulin-like growth factors (IGFs), a principal anabolic system that is involved in protein synthesis and that has downregulation that is implicated in muscle loss in animal models of uremia, has previously not been assessed in vivo in HD patients. <h3>Methods</h3> Seventeen HD patients were compared cross-sectionally with 17 age-, sex-, and body mass index-matched healthy controls. Body composition was assessed by dual energy x-ray absorptiometry and bioelectrical impedance spectrometry; functional capacity by hand grip strength, quadriceps strength, and 30-second sit-to-stand test; systemic inflammation by tumor necrosis factor-α (TNF-α) and TNF receptor 1 (TNFR1); serum and muscle IGF-I and IGFBP-3 by radioimmunoassay; and fragmentation of serum IGFBP-3 by Western immunoblotting. <h3>Results</h3> Appendicular lean mass was significantly decreased in HD patients compared with controls (17.6 ± 0.9 versus 21.5 ± 1.5 kg, <i>P</i> < .05), as were all measures of functional capacity (<i>P</i> < .01 to .001), and highly significant positive correlations between appendicular lean mass and functional capacity were evident (appendicular lean mass and hand-grip strength, quadriceps strength, 30-second sit-to-stand test, all <i>P</i> < .001). TNF-α and TNFR1 were elevated in patients (<i>P</i> < .001). Although serum IGF-I and IGFBP-3 levels did not differ between the groups (<i>P</i> = .295 and .379 respectively), fragmented IGFBP-3 levels were increased (53.1 ± 16.0 versus 29.81 ± 15.3%, <i>P</i> < .005). In contrast, muscle IGF-I was substantially diminished in the patient group (n = 7) relative to control (<i>n</i> = 5) levels (0.84 ± 0.06 versus 2.78 ± 1.80 pg/μg, <i>P</i> < .05). <h3>Conclusions</h3> We provide evidence of reduced IGF-I in HD patients' skeletal muscle that may be a causal factor in the muscle wasting characteristic of this population. Future research should determine the exact consequences and causes of alterations to the muscle IGF system in HD patients.

Effects of Reduced Dialysate Calcium on Calcium-Phosphorus Product and Bone Metabolism in Hemodialysis Patients

Background: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. Study Design: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D₃ (25-vit D₃), 1,25-(OH)₂-vitamin D₃ (1,25-vit D₃), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. Results: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol²/l² (at 18 months), whereas PTH increased from 81 ± 57 pg/ml at baseline to 236 ± 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D₃ and 1,25-vit D₃ subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 ± 0.9 ng/ml, after 18 months: 1.1 ± 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. Conclusion: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.

Vitamin C and E supplements improve the impaired antioxidant status and decrease plasma lipid peroxides in hemodialysis patients☆

This study investigated the supplementation with vitamin C or/and E on the antioxidant system in hemodialysis patients. Thirty-eight hemodialysis patients (27 males and 11 females) with the average of 60 years old were divided into four groups: placebo (400 mg starch/time), vitamin C (400 mg/time)-, vitamin E (400 mg d,l- α-tocopheryl acetate/time)-, and vitamin C (400 mg/time) + E (400 mg d,l- α-tocopheryl acetate/time)-supplemented groups for 6-week supplementation. The patients orally received three capsules of placebo or antioxidant(s) three times a week after finishing hemodialysis. Thirty-six healthy subjects (22 males and 14 females) with the average of 58 years old were recruited as the control group. Hemodialysis patients significantly decreased plasma vitamin C by 32%, erythrocyte glutathione by 26%, and plasma total antioxidant status by 9%, but increased plasma lipid peroxide levels by 102% compared with the control group at the baseline. The levels of plasma vitamin C and total antioxidant status significantly decreased by 24% and 18%, respectively, from the post-dialysate compared with those from the pre-dialysate. At week 6, vitamin C + E-supplemented group significantly increased plasma vitamin C and E, erythrocyte glutathione, and plasma antioxidant status, and inhibited plasma lipid peroxides compared with placebo group. Additionally, vitamin C + E-supplemented group had higher plasma vitamin C, vitamin E, and total antioxidant status, and lower plasma lipid peroxides than placebo group even at least 2 weeks after the termination of the supplements. Therefore, antioxidant vitamin supplements could improve antioxidant status and decrease lipid peroxides of hemodialysis patients.