Effects of a Combined Intradialytic Exercise Training Program on Functional Capacity and Body Composition in Kidney Transplant Candidates.

Chronic kidney disease (CKD) leads to gradual muscle mass loss, which is strongly associated with lower functional capacity, which limits a patient's daily activities. The aim of the present study is to examine the effects of a 4-month intradialytic exercise program on the functional capacity and body composition of kidney transplant (KT) candidates. Twenty-nine male patients on hemodialysis (HD) waiting for a kidney transplant, with a mean age of 53.86 ± 9.56 years old and BMI 27.11 ± 5.55 kg/m2, were randomly assigned into the following two groups: A (nA = 15 HD patients), who followed a 4-month intradialytic exercise program combining aerobic and resistance training, with a supervised, progressively increasing workload, and B (nB = 14 HD patients), who continued to receive usual care. At baseline and the end of the study, the KT candidates underwent a 6-min walking distance (6-MWD), and a 10-repetition sit-to-stand test (10-STS) to access physical function, a handgrip strength (HGS) test to evaluate the muscle strength of the non-fistula hand. Moreover, the bioelectrical impedance analysis (BIA) was performed to assess body composition indices, such as body fat (BF), body fat mass index (BFMI), fat-free mass index (FFMI), body cell mass (BCM), basal metabolic rate (BMR), extracellular water (ECW), intracellular water (ICW), total body water (TBW) and phase angle (PhA). Following the exercise program, group A showed favorable improvements in HGS (from 26.59 ± 9.23 to 28.61 ± 9.58 kg, p < 0.05) and 6-MWD (from 427.07 ± 7.66 to 468.16 ± 11.39 m, p < 0.05). Intergroup results from 6-MWD showed a statistically significant difference (Δp = 0.04), at the end of the study. Moreover, group A results from BIA revealed a significant increase of BMR by 2.4% (p < 0.05), ECW by 3.6% (p = 0.01), ICW by 3.8% (p = 0.01), TBW by 4.1% (p = 0.01), lean mass by 2.7% (p = 0.01), and PhA by 13.3% (p = 0.04), while a reduction in BF by 5.0% (p = 0.01) and BFMI by 6.6% (p = 0.03) was also noticed. At the end of the study, group A showed statistical differences in BMR (Δp = 0.01), BMR/BW (Δp = 0.01), dry lean (Δp = 0.01), and PhA (Δp = 0.03), compared to the group B. Linear regression analysis in group A after training showed positive correlations between HGS and both PhA (r = 0.52, p = 0.04) and FFMI (r = 0.64, p = 0.01), and a strong negative correlation between 6-MWT and BF (r = −0.61, p = 0.01). In conclusion, a 4-month intradialytic exercise program can enhance body composition and some physical parameters in HD patients awaiting kidney transplantation.

Phosphorus nutritional knowledge among dialysis health care providers and patients: A multicenter observational study.

BACKGROUND-AIMS: Phosphorus nutritional knowledge level of hemodialysis patients and renal nurses has been found to be low, while respective knowledge of nephrologists has not been studied yet. There are equivocal results regarding the association of phosphorus nutritional knowledge level and serum phosphorus values. The aim of this study was to assess phosphorus nutritional knowledge of hemodialysis patients, nephrologists and renal nurses and seek potential interventions to improve patients' adherence to phosphorus and overall nutritional guidelines. METHODS: This cross-sectional observational study was conducted on sixty eight hemodialysis patients, 19 renal nurses and 11 nephrologists who were recruited from 3 hemodialysis units in Greece. Phosphorus nutritional knowledge of the participants was assessed by a 25-item item questionnaire (CKDKAT-N) which included 15 questions on phosphorus and 10 questions on protein, sodium, and potassium knowledge. RESULTS: Nephrologists had higher CKDKAT-N total (19.1 ± 3.6 vs 14.1 ± 2.8 and 13.2 ± 2.8, P < 0.01) and phosphorus knowledge scores (10.6 ± 2.7 vs 7.6 ± 2.2 and 7.3 ± 2.0, P < 0.01) compared to renal nurses and patients respectively. There were no differences in total and phosphorus knowledge scores between nurses and patients. Patients and nurses answered correctly significantly less questions regarding phosphorus compared with the rest of the questions (P < 0.01) while no such difference was found in nephrologists. Serum phosphorus was positively correlated with phosphorus knowledge score (r = 0.31, P = 0.02), and negatively correlated with patient age (r = -0.34, P < 0.05). None of the patients, 11% of the nurses and 27% of the nephrologists answered correctly all three questions regarding P, K and Na dietary recommendations (P < 0.01). CONCLUSIONS: The study confirms that hemodialysis patients have low renal nutrition knowledge while higher nutritional phosphorus knowledge does not lead to lower serum phosphorus values. Alarmingly, renal nurses have been found to have a similar level of knowledge with hemodialysis patients, something that needs to be taken into account when training the new dialysis staff. Nephrologists have superior knowledge; however they are still lacking essential nutritional knowledge that could affect patients' and nurses' overall understanding. Continuing education on nutrition of nephrologists and renal nurses could improve nutrition care of hemodialysis patients.

Ambulatory Pulse Wave Velocity Is a Stronger Predictor of Cardiovascular Events and All-Cause Mortality Than Office and Ambulatory Blood Pressure in Hemodialysis Patients.

Arterial stiffness and augmentation of aortic blood pressure (BP) measured in office are known cardiovascular risk factors in hemodialysis patients. This study examines the prognostic significance of ambulatory brachial BP, central BP, pulse wave velocity (PWV), and heart rate-adjusted augmentation index [AIx(75)] in this population. A total of 170 hemodialysis patients underwent 48-hour ambulatory monitoring with Mobil-O-Graph-NG during a standard interdialytic interval and followed-up for 28.1±11.2 months. The primary end point was a combination of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. Secondary end points included: (1) all-cause mortality; (2) cardiovascular mortality; and (3) a combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, coronary revascularization, or hospitalization for heart failure. During follow-up, 37(21.8%) patients died and 46(27.1%) had cardiovascular events. Cumulative freedom from primary end point was similar for quartiles of predialysis-systolic BP (SBP), 48-hour peripheral-SBP, and central-SBP, but was progressively longer for increasing quartiles for 48-hour peripheral-diastolic BP and central-diastolic BP and shorter for increasing quartiles of 48-hour central pulse pressure (83.7%, 71.4%, 69.0%, 62.8% [log-rank P=0.024]), PWV (93.0%, 81.0%, 57.1%, 55.8% [log-rank P<0.001]), and AIx(75) (88.4%, 66.7%, 69.0%, 62.8% [log-rank P=0.014]). The hazard ratios for all-cause mortality, cardiovascular mortality, and the combined outcome were similar for quartiles of predialysis-SBP, 48-hour peripheral-SBP, and central-SBP, but were increasing with higher ambulatory PWV and AIx(75). In multivariate analysis, 48-hour PWV was the only vascular parameter independently associated with the primary end point (hazard ratios, 1.579; 95% confidence intervals, 1.187-2.102). Ambulatory PWV, AIx(75), and central pulse pressure are associated with increased risk of cardiovascular events and mortality, whereas office and ambulatory SBP are not. These findings further support that arterial stiffness is the prominent cardiovascular risk factor in hemodialysis.

Corticosteroids and ciclosporin A in idiopathic membranous nephropathy: higher remission rates of nephrotic syndrome and less adverse reactions than after traditional treatment with cytotoxic drugs.

BACKGROUND/AIM: Idiopathic membranous nephropathy, the most common cause of nephrotic syndrome in adults, has been traditionally treated with corticosteroids and cytotoxic drugs. Ciclosporin A (CsA) is used in resistant cases, but also as a first-line treatment, due to the serious side effects of cytotoxic drugs. In this study, the remission rates of nephrotic syndrome and the incidence of side effects of corticosteroids and low CsA doses are compared with those after treatment with cytotoxic drugs. METHODS: Seventy-seven nephrotic patients with well-preserved renal function who were treated with methylprednisolone and CsA (n = 46) or cytotoxic drugs (n = 31) were studied. The effects of treatments were estimated on the basis of remission rates of nephrotic syndrome and preservation of the renal function. RESULTS: Remission (complete or partial) of nephrotic syndrome was observed in 85% of the patients treated with CsA and in 55% of the patients treated with cytotoxic drugs (p < 0.01). Deterioration of the renal function, more common in patients with multiple relapses and interstitial fibrosis, was observed in 26 and 23% of the patients, respectively (p = NS). Serious side effects and discontinuation of treatment were more frequent in patients treated with cytotoxic drugs (10 vs. 4%). CONCLUSION: The combination of corticosteroids with CsA represents a better regimen for patients having idiopathic membranous nephropathy, since it is associated with higher remission rates of nephrotic syndrome and less severe side effects than corticosteroids and cytotoxic drugs.

Enhancement of the transmesothelial resistance of the parietal sheep peritoneum by epinephrine in vitro: ussing-type chamber experiments.

The peritoneal mesothelium constitutes an ion transport barrier that is taken advantage of in peritoneal dialysis. The aim of this study was to investigate the effects of epinephrine on the electrical transmesothelial resistance (R(TM)) of the isolated parietal sheep peritoneum by means of Ussing-type chamber experiments. Intact parietal (diaphragmatic) peritoneal samples were obtained from adult sheep immediately after sacrifice and transferred within 0.5 h to the laboratory in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5), bubbled with 95% O2-5% CO2. A parietal peritoneal planar sheet was mounted in a Ussing-type chamber. Epinephrine (10(-7) M) was added to the apical and the basolateral side. The R(TM) was measured before and serially after the addition of epinephrine for 30 min. As active ion transport is temperature-dependent, all measurements were performed at 37 degrees C. The results were calculated as means with standard errors (x +/- SE) of six independent experiments. The control R(TM) was 20.05 +/- 0.61 ohm x cm2. The addition of epinephrine to the basolateral side within 1 min induced an increase of R(TM) to 21.8 +/- 0.45 ohm x cm2, which decreased thereafter progressively to reach control values again after 15 min. A similar effect of epinephrine on the apical side was apparent with a rapid rise of R(TM) to 22.5 +/- 0.66 ohm x cm2 and a subsequent decrease (P < 0.05). A clear association between the R(TM) and active ion transport was established from previous studies. The results of our study indicate a rapid action of epinephrine on the parietal peritoneum permeability.

Endothelin-1 plasma levels in hemodialysis treatment--the influence of type 2 diabetes.

In patients on chronic hemodialysis the prevalence of atherosclerosis is increased and is by far the leading cause of morbidity and mortality. Endothelin-1, an endothelium-derived peptide with vasoconstrictive and mitogenic effects on vascular smooth muscles, is involved in the pathogenesis of atherosclerosis. The aim of the present study was to investigate the time course of plasma endothelin-1 levels during a hemodialysis session and to explore the influence of preexisting type 2 diabetes mellitus. Forty-five clinically stable hemodialysis patients (21 females, 24 males; mean age 62 +/- 12 years) were evaluated. Patients with type 2 diabetes (n= 11) were compared with the group of patients without diabetes (n=34). Relative blood volume (BV) changes (hemoglobinometry) and blood pressure (BP) was measured. Samples were taken before, every hour during, and after hemodialysis. Plasma endothelin-1 levels were measured by enzyme-linked immunoassay (ELISA) and results were corrected according to hemoconcentration. Hemodialysis with an ultrafiltration of 2215 +/- 952 mL was performed. Total BV at the end of hemodialysis was 89.3% +/- 8.3% of the pretreatment volume. Plasma endothelin-1 was enhanced in hemodialysis patients compared to normal subjects and increased from 1.28 +/- 0.47 before to 1.44 +/- 0.54 pg/mL (ref. 0.3-0.9) at the end of hemodialysis (p<0.05). The BV change (r=0.41) and the BP (mean BP: r=0.34) correlated with plasma endothelin-1 at the end of hemodialysis (p<0.05). The levels of endothelin-1 were significantly higher in the group of dialysis patients with type 2 diabetes compared to nondiabetics in all measurements (p<0.05). These findings suggest a potential role of endothelin-1 in the pathogenesis of vascular dysfunction in diabetes mellitus. The dialysis procedure per se, through vasoconstriction due to BV decrease, local endothelial injury (a.v. fistula), or bioincompatibility reactions (foreign surface contact) may additionally alter endothelial cell functions.

Resistin serum levels are increased but not correlated with insulin resistance in chronic hemodialysis patients.

BACKGROUND/AIMS: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. METHODS: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5+/-15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41+/-31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6+/-12.1 years). BMI (kg/m(2)) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. RESULTS: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2+/-6.2 vs. 3.9+/-1.8 ng/ml; p<0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2+/-6.2 vs. 18.7+/-5.0 ng/ml; p=0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4+/-21.5 vs. 10.5+/-5.9 microg/ml; p<0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r=-0.527, p=0.002), the HOMA-R (r=-0.378, p<0.05) and the fasting insulin levels (r=-0.397, p<0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2+/-3.9 mmol.microIU/ml; r=-0.098, p=0.59), insulin levels (13.3+/-14.4 mU/l; r=-0.073, p=0.69), glucose levels (89+/-13 mg/dl; r=-0.049, p=0.78), BMI (25.6+/-3.7 kg/m(2); r=-0.041, p=0.82) and body fat content (26.4+/-8.4%; r=-0.018, p=0.94) on the other hand. CONCLUSION: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.

Hemodialysis procedure does not affect the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease.

Atherosclerosis is by far the leading cause of mortality and morbidity in patients with end stage renal disease undergoing chronic hemodialysis (HD). Vascular endothelial cell adhesion molecules like the intercellular adhesion molecule-1 (ICAM-1) and the vascular cell adhesion molecule-1 (VCAM-1) are involved in the pathogenesis of atherosclerosis. Their soluble forms (sICAM-1, sVCAM-1) are considered potential serum markers of endothelial activation and atherosclerosis. The aim of this study was to clarify the influence of the HD procedure on the levels of sICAM-1 and sVCAM-1 in patients with end stage renal disease. We evaluated 35 clinically stable patients (18 males, 17 females, mean age 61 +/- 12) on chronic HD treatment. Diabetes mellitus coexisted in eight patients and arterial hypertension in 23 patients. Blood was drawn before, every hour during, and after a single HD session in each patient. Low-flux cuprophane dialyzers (GFS 12, Gambro, Lund, Sweden) were used in 22 and high-flux polysulfone dialyzers (Hemoflow F 60S, Fresenius, Oberursel, Germany) in 13 cases. At 30 min into the HD session (n=31, 20 low-flux HD, 11 high-flux HD) blood was drawn simultaneously from the entrance and the exit line of the dialyzer. From all these samples, serum concentrations of sICAM-1 and sVCAM-1 were determined by commercially available enzyme immunoassays (ELISA, R&D Systems, Minneapolis, USA). Results were corrected according to hemoconcentration, where appropriate. Plasma levels of sVCAM-1 were elevated in patients with end stage renal disease before the beginning of the dialysis session when compared to healthy controls (1449 +/- 497 ng/mL vs. 691 +/- 118 ng/mL). On the contrary, such an elevation was not found in the case of sICAM-1 (231 +/- 58.5 ng/mL vs. 236.4 +/- 96.8 ng/mL in healthy controls). These levels remained stable in all measurements throughout the dialysis procedure. Furthermore, serum sICAM-1 and sVCAM-1 levels remained unaltered after the passage of the dialyzer. The levels of sICAM-1 and sVCAM-1 were not influenced by the existence of diabetes mellitus, hypertension, or by the utilization of biocompatible, high flux dialyzers. Our study confirms that in chronic HD patients serum levels for sVCAM-1 are elevated. The levels of adhesion molecules are not affected by the HD procedure. These findings probably can be attributed to a decreased renal clearance or catabolism of sICAM-1 and sVCAM-1 and to the different sources of the two molecules. Neither coexisting diabetes mellitus nor arterial hypertension influences the circulating levels of these adhesion molecules. The functional role of sVCAM-1 and sICAM-1, the exact renal contribution to their metabolism, and their role as markers of atherosclerosis in chronic renal disease need further evaluation.

Effect of 1-year oral alpha-tocopherol administration on anticardiolipin antibodies in hemodialysis patients.

BACKGROUND: Anticardiolipin antibodies (ACA) have been related to an increased incidence of thrombotic episodes and atherosclerosis progression. ACA levels are elevated in hemodialysis (HD) patients. Atheroembolic episodes are the major cause of morbidity and mortality in this population. Oxidative stress has been implicated in ACA formation, and it is increased in HD patients. Vitamin E is a known antioxidant factor. In this study, the effects of prolonged oral alpha-tocopherol administration on ACA levels were evaluated. METHODS: Serum anticardiolipin IgG antibodies (ACA-IgG) and IgM antibodies (ACA-IgM) levels were evaluated in 27 stable HD patients and 22 healthy volunteers. Then measurements were performed in the patients' group after oral administration of alpha-tocopherol at a dose of 500 mg/d for a 1-year period. ACA levels were assessed by solid-phase enzyme immunoassay. RESULTS: ACA-IgG levels were higher in HD patients compared with control (13.3 +/- 6.64 GPL/mL vs. 7.727 +/- 18.305 GPL/mL, p < .001). This was not the case for ACA-IgM levels (2.96 +/- 4.18 MPL/mL vs. 1.386 +/- 2.636 MPL/mL, p=.17). alpha-Tocopherol administration resulted in a further increase in ACA-IgG (26.7 +/- 14.7 GPL/mL vs. 13.3 +/- 6.64 GPL/mL, p < .001) and ACA-IgM levels (8.17 +/- 1.95 MPL/mL vs. 2.96 +/- 4.18 MPL/mL, p < .001) in HD patients. CONCLUSIONS: Prolonged oral alpha-tocopherol administration in HD patients increases ACA levels. The mechanism and the clinical significance of this finding need further evaluation.

Influence of the sodium transport inhibition by amiloride on the transmesothelial resistance of isolated visceral sheep peritoneum.

The peritoneal mesothelium is a barrier to ion transport in peritoneal dialysis. In the present study, we used Ussing chamber experiments to investigate the effect of amiloride on the transmesothelial electrical resistance (R(TM)) of isolated visceral sheep peritoneum. Peritoneal samples from the omentum of adult sheep were isolated directly after the death of the animals and were transferred to the laboratory within 30 minutes in a cooled Krebs-Ringer bicarbonate solution (4 degrees C, pH 7.5) bubbled with 95% O2/5% CO2. A visceral peritoneal planar sheet was mounted in an Ussing-type chamber and amiloride (10(-3) mol/L) was added apically and basolaterally. The R(TM) was measured before and serially for 30 minutes after the addition of amiloride. Because active ion transport is temperature dependent, the Ussing chambers were held at 37 degrees C. The results presented are the means + standard error of 12 experiments. The control R(TM) (before the addition of amiloride) was 21.86 +/- 0.46 omega x cm2. Basolateral addition of amiloride induced, within 1 minute, an increase in R(TM) to 27.26 +/- 0.39 omega x cm2, a level that persisted throughout the experiment. When amiloride was added apically, the results were similar with a rapid rise of R(TM) to 24.18 +/- 0.9 omega x cm2 and subsequent value persistence (p < 0.05). A clear association between R(TM) and active ion transport was shown in previous studies. The results of the present study indicate rapid action of amiloride on the permeability of the visceral peritoneum. The observed increase in the R(TM) indicates the existence of amiloride-sensitive sodium channels in the visceral peritoneal membrane. The clinical implications of these results should be further investigated.