Phenotypes influencing low physical activity in maintenance dialysis.

OBJECTIVE: The "Pas à Pas" initiative aimed at evaluating the weekly physical activity (PA) and its determinants in a large cohort of dialysis patients. SETTING: Physical inactivity is a risk factor for mortality in maintenance dialysis patients and is still poorly documented in this population. DESIGN: A prospective national epidemiological study was performed. SUBJECTS: A total of 1,163 patients on maintenance dialysis (hemodialysis and peritoneal dialysis) were included. INTERVENTION AND MAIN OUTCOME MEASURE: PA was recorded during seven consecutive days using a pedometer to measure daily step numbers. RESULTS: Median age was 63 years (Q1 51-Q3 75). Sixty-three percent were sedentary (<5000 steps/day) with a median of 3,688 steps/day (1,866-6,271)]. PA level was similar between hemodialysis patients and those on peritoneal dialysis (3,693 steps [1,896-6,307] vs. 3,320 [1,478-5,926], P = .33). In hemodialysis patients, PA was lower on dialysis days compared with nondialysis days (2,912 [1,439-5,232] vs. 4,054 [2,136-7,108], respectively, P < .01). PA gradually decreased with age, 57% being sedentary between 50 and 65 years and 83% of patients after 80 years. Beyond this age effect, we identified, for the first time, specific phenotypes of patients with lower PA, such as inflammation, cardiovascular disease, protein energy wasting, obesity, and diabetes. By contrast, previous kidney transplantation and a higher muscle mass were associated with higher PA. CONCLUSIONS: Dialysis patients present a very low level of PA with high sedentary. Acting on patient's modifiable phenotypes may help to increase PA to improve morbidity, mortality, and quality of life.

Anthropometric indicators predict metabolic syndrome diagnosis in maintenance hemodialysis patients

Obesity has been considered the key in metabolic syndrome (MetS) development, and fat accumulation may be responsible for the occurrence of metabolic abnormalities in hemodialysis patients. The use of gold-standard methods to evaluate obesity is limited, and anthropometric measures may be the simplest methods. However, no study has investigated the association between anthropometric indexes and MetS in these patients. Therefore, the aim was to determine which anthropometric indexes had the best association and prediction for MetS in patients undergoing hemodialysis. Cross-sectional study that included patients older than 18 years, undergoing hemodialysis for at least 3 months. Patients with liver disease and cancer or those receiving corticosteroids or antiretroviral therapy were excluded. Diagnostic criteria from Harmonizing Metabolic Syndrome were used for the diagnosis of MetS. Anthropometric indexes evaluated were body mass index (BMI); percent standard of triceps skinfold thickness and of middle arm muscle circumference; waist circumference (WC); sagittal abdominal diameter; neck circumference; waist-to-hip, waist-to-thigh, and waist-to-height ratios; sagittal index; conicity index; and body fat percentage. Ninety-eight patients were included, 54.1% male, and mean age was 57.8 ± 12.9 years. The prevalence of MetS was 74.5%. Individuals with MetS had increased accumulation of abdominal fat and general obesity. Waist-to-height ratio was the variable independently associated with MetS diagnosis (odds ratio, 1.21; 95% confidence interval, 1.09-1.34; P < .01) and that better predicts MetS, followed by WC and BMI (area under the curve of 0.840, 0.836, and 0.798, respectively, P < .01). Waist-to-height ratio was the best anthropometric predictor of MetS in maintenance hemodialysis patients.

Glucocorticoid resistance in dialysis patients may impair the kidney allograft outcome

This study examines in vitro steroid sensitivity in chronic renal failure ( CRF) patients and its influence on the allograft outcome. We determined the inhibitory effect of dexamethasone ( DEX) on concanavalin A ( Con-A)-stimulated peripheral blood mononuclear cell ( PBMC) proliferation, and glucocorticoid receptor` ( GR) number of binding sites ( B-max) and affinity ( K-d) in 28 CRF patients and 40 normal healthy controls. Based on K-d values > 95th percentile from controls, patients were divided into two groups: glucocorticoid resistant ( n = 11) and glucocorticoid sensitive ( n = 17). Patients were followed during 18 months post-transplantation observing acute rejection episodes ( ARE), chronic allograft nephropathy ( CAN), allograft failure and death. The DEX concentration that caused 50% inhibition of Con-A-stimulated PBMC proliferation ( IC50) was higher in CRF than in healthy controls ( 2.2 x 10(-5) +/- 1.0 x 10(-5) versus 8.3 x 10(-6) +/- 4.2 x 10(-6) mol/ L, P = 0.02). Values of Kd ( 12.4 +/- 1.8 versus 7.2 +/- 0.9 nM) and Bmax ( 7.7 +/- 1.1 versus 4.1 +/- 0.3 fmol/ mg protein) were higher in CRF patients ( P = 0.02 and P = 0.001, respectively). There were higher incidences of ARE ( P = 0.02) and CAN ( P = 0.002) in the glucocorticoid-resistant group. Univariate and multivariate logistic regression showed that Kd was an independent predictor of ARE ( OR 8.8, P= 0.03) aswell as of CAN ( OR 16.5, P= 0.01). In conclusion, we observed glucocorticoid resistance in a subgroup of CRF patients undergoing dialysis, which led to a higher morbidity due to ARE and CAN in an 18-month follow-up period.

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload

Background Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12–16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. Methods A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 ± 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. Results Icodextrin significantly increased peritoneal ultrafiltration (885 ± 210 ml to 1454 ± 215 ml, p < 0.05) and reduced mean arterial pressure (106 ± 4 to 96 ± 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 ± 0.7% to 7.9 ± 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0–17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13–5.62, p < 0.05). Conclusions Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Achieving K/DOQI Targets with Cinacalcet in Dialysis Patients with Secondary Hyperparathyroidism. A Portuguese Observational Study

Secondary hyperparathyroidism is a common complication of chronic kidney disease. The elevated serum intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product have been independently associated with an increased relative risk of mortality. The standard therapy for secondary hyperparathyroidism, including active vitamin D analogues and phosphate binders, is often insufficient to allow patients to achieve the recommended Kidney Disease Outcomes Quality Initiative targets for bone and mineral metabolism. Randomised controlled phase III clinical studies in chronic kidney disease patients with secondary hyperparathyroidism have shown that cinacalcet treatment increases the proportion of patients achieving the recommended Kidney Disease Outcomes Quality Initiative targets for intact parathyroid hormone, phosphorus, calcium and calcium x phosphorus product. Aims: This observational multicentre study aims to evaluate cinacalcet’s ability to achieve and maintain Kidney Disease Outcomes Quality Initiative targets in a population with secondary hyperparathyroidism on chronic haemodialysis in Portugal. Patients and Methods: Patients on chronic dialysis that received cinacalcet during a free sampling programme were enrolled. Retrospective and prospective monthly data were collected from 3 months before until 6 months after the beginning of cinacalcet treatment. Additional assessment included a 12 month evaluation of all parameters. Results: 140 dialysis patients with secondary hyperparathyroidism were enrolled, 60% male, mean age 57.4±14.1 years. The mean intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product values at baseline were 751.7±498.8 pg/ml, 9.7±3.8 mg/dl, 5.5±1.5 mg/dl, and 52.7±25.3 mg2/dl2, respectively. After 6 months’ cinacalcet treatment, 26.2%, 53.6%, 59.3%, and 81.0% of the patients achieved the Kidney Disease Outcomes Quality Initiative recommended levels for intact parathyroid hormone, calcium, phosphorus, and calcium x phosphorus product, respectively. The mean dose of cinacalcet at 6 months was 57.1±29.7 mg/day. Conclusions: The use of cinacalcet in clinical practice is an effective option for the treatment of secondary hyperparathyroidism in chronic dialysis patients, allowing more patients to reach and maintain the Kidney Disease Outcomes Quality Initiative targets.

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

BACKGROUND: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity. TRIAL DESIGN: This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects. METHODS: At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored. RESULTS: Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63×10-3 to 0.76×10-3. This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP. CONCLUSIONS/LIMITATIONS: Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation. TRIAL REGISTRATION: ClinicalTrial.gov NCT01253928.

GB virus C/hepatitis G virus infection in dialysis patients and kidney transplant recipients in central Brazil

In order to investigate the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) infection in dialysis patients and kidney transplant recipients in Central Brazil and also to analyze the virus genotypes distribution, a total of 123 patients including 98 on hemodialysis, 13 on continuous ambulatory peritoneal dialysis treatment, and 12 who received kidney transplantation were interviewed in one unit of dialysis treatment in Goiânia city. Blood samples were collected and serum samples tested for GBV-C/HGV RNA by polymerase chain reaction. Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis. Eighteen samples were GBV-C/HGV RNA-positive, resulting in an overall prevalence of 14.6% (95% CI: 9.2-21.7). A high positivity for GBV-C/HGV RNA was observed in patients who had received kidney transplant (16.7%), followed by those on hemodialysis (15.3%), and peritoneal dialysis (7.7%). RFLP analysis revealed the presence of genotypes 1, 2, and 3 of GBV-C/HGV; more precisely, 9 (50%) samples were found belonging to the 2b subtype, 4 (22%) to the 2a subtype, 3 (17%) to genotype 1, and 2 (11%) to genotype 3. The present data indicate an intermediate prevalence of GBV-C/HGV infection among dialysis patients and kidney transplant recipients in Central Brazil. Genotype 2 (subtype 2b) seems to be the most prevalent GBV-C/HGV genotype in our region.

Improvement in secondary hyperparathyroidism due to drug adherence monitoring in dialysis patients.

BACKGROUND: Poor medication adherence is a frequent cause of treatment failure but is difficult to diagnose. In this study we have evaluated the impact of measuring adherence to cinacalcet-HCl and phosphate binders in dialysis patients with uncontrolled secondary hyperparathyroidism. METHODS: 7 chronic dialysis patients with iPTH-levels >= 300 pg/ml despite treatment with >= 60 mg cinacalcet-HCl were included. Medication adherence was measured using the "Medication Events Monitoring System" during 3 months, followed by another 3-month period without monitoring. The adherence results were monthly discussed with the patients, as well as strategies to improve them. RESULTS: During monitoring, the percentage of prescribed doses taken was higher for cinacalcet-HCl (87.4%) and sevelamer (86.3%) than for calcium acetate (76.1%), as was the taking adherence (81.9% vs. 57.3% vs. 49.1%) but not the percentage of drug holidays (12.3% vs. 4.5% vs. 3.6%). Mean PO4 levels (from 2.24 +/- 0.6 mmol/l to 1.73 +/- 0.41 mmol/l; p = 0.14) and Ca++ x PO4 product (4.73 +/- 1.43 to 3.41 +/- 1.04 mmol2/l2; p = 0.12) improved and iPTH-level improved significantly from 916 +/- 618 pg/ml to 442 +/- 326 pg/ml (p = 0.04), without any change in medication. However, as drug monitoring was interrupted, all laboratory parameters worsened again. CONCLUSIONS: Assessment of drug adherence helped to document episodes of non-compliance and helped to avoid seemingly necessary dose increases.

Optimal and continuous anaemia control in a cohort of dialysis patients in Switzerland.

BACKGROUND: Guidelines for the management of anaemia in patients with chronic kidney disease (CKD) recommend a minimal haemoglobin (Hb) target of 11 g/dL. Recent surveys indicate that this requirement is not met in many patients in Europe. In most studies, Hb is only assessed over a short-term period. The aim of this study was to examine the control of anaemia over a continuous long-term period in Switzerland. METHODS: A prospective multi-centre observational study was conducted in dialysed patients treated with recombinant human epoetin (EPO) beta, over a one-year follow-up period, with monthly assessments of anaemia parameters. RESULTS: Three hundred and fifty patients from 27 centres, representing 14% of the dialysis population in Switzerland, were included. Mean Hb was 11.9 +/- 1.0 g/dL, and remained stable over time. Eighty-five % of the patients achieved mean Hb &gt;or= 11 g/dL. Mean EPO dose was 155 +/- 118 IU/kg/week, being delivered mostly by subcutaneous route (64-71%). Mean serum ferritin and transferrin saturation were 435 +/- 253 microg/L and 30 +/- 11%, respectively. At month 12, adequate iron stores were found in 72.5% of patients, whereas absolute and functional iron deficiencies were observed in only 5.1% and 17.8%, respectively. Multivariate analysis showed that diabetes unexpectedly influenced Hb towards higher levels (12.1 +/- 0.9 g/dL; p = 0.02). One year survival was significantly higher in patients with Hb &gt;or= 11 g/dL than in those with Hb &lt;11 g/dL (19.7% vs 7.3%, p = 0.006). CONCLUSION: In comparison to European studies of reference, this survey shows a remarkable and continuous control of anaemia in Swiss dialysis centres. These results were reached through moderately high EPO doses, mostly given subcutaneously, and careful iron therapy management.

Influence of protein intake and muscle mass on survival in chronic dialysis patients

Introduction: Some studies suggest that high body mass index (BMI) confers survival advantage in dialysis patients, but BMI does not differentiate muscle from fat mass, and the survival advantage conferred by its increase seems to be limited to patients with high muscle mass. Thus, discriminating body components when evaluating nutritional status and survival is highly important. This study evaluated the influence of nutritional parameters on survival in patients on chronic dialysis. Subjects and methods: Anthropometry, bioimpedance, biochemistry, and dietary recall were used to investigate the influence of nutritional parameters on survival in 79 prevalent patients on chronic dialysis. Results: Protein intake <1.2 g/kg/day and creatinine <9.7 mg/dL were independent predictors of mortality in all patients. Regarding dialysis method, protein intake <1.2 g/kg/ day was predictive of mortality among hemodialysis patients, and percent standard mid-arm muscle circumference <80% was identified as a risk factor among peritoneal dialysis patients. Conclusion: Higher muscle mass, possibly favored by a higher protein intake, conferred survival advantage in dialysis patients.

Identification and antimicrobial susceptibility of Staphylococcus from home-treated peritoneal dialysis patients

Staphylococcus aureus is the main agent of infections during peritoneal dialysis (PD). The presence of S. aureus in the nasal cavity has been extensively studied and suggested as a risk factor of dialysis-related infections, whereas coagulase-negative Staphylococcus (CNS) species are frequently considered part of the normal human microbiota. The aim of this study was to identify Staphylococcus in the nasal cavity, pericatheter skin and peritoneal effluent from PD patients, as well as to evaluate the antimicrobial activity evolution in vitro. Thirty-two chronic PD patients were observed during 12 months and had nasal and pericatheter skin samples collected for culture. When peritonitis was detected, samples were also collected from the peritoneal effluent for culture. The activity of several antimicrobial drugs (penicillin G, oxacillin, cephalothin, ofloxacin, netilmicin and vancomycin) against different Staphylococcus species was measured by using the agar drug diffusion assay (Kirby-Bauer method). Staphylococcus was separated into S. aureus, S. epidermidis and other CNS species in order to determine the in vitro resistance level. S. epidermidis resistance to oxacillin progressively increased during the study period (p < 0.05). Resistance to ofloxacin was inexpressive, whereas resistance to netilmicin and vancomycin was not detected. of the oxacillin-resistant species (n = 74), 83% were S. epidermidis, 13% other CNS and 4% S. aureus (p < 0.05). Regarding multidrug resistant strains (n = 45), 82% were S. epidermidis, 13% other CNS, and 5% S. aureus (p < 0.05). This study shows the relevance of resistance to oxacillin and CNS multi-drug resistance, particularly concerning S. epidermidis, in PD patients.

Prolactin and zinc in dialysis patients

The objectives of the present study were to investigate the frequencies of hyperprolactinemia and hypozincemia in patients undergoing hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), the associations between blood levels of zinc (Zn2+) and hormones, and dietary zinc intake amount and its relation to zincemia. We studied 28 patients (14 HD and 14 CAPD) who had their blood levels of Zn2+, prolactin (PRL), parathyroid hormone (PTH), and gonadotropins (LH, FSH) evaluated. Thirteen patients had dietary nutrient amounts evaluated from a 3-d nutritional record. Hyperprolactinemia occurred in 29% patients (HD = CAPD), hypozincemia in 62% (20% HD and 42% CAPD), and low dietary Zn2+ intake in 90% of patients. No correlation among blood concentration of Zn2+ and PRL, PTH, LH, and FSH were observed in the two modalities of dialysis or between zincemia and Zn2+ ingestion. We concluded that the occurrence of hyperprolactinemia and hypozincemia were not related to dialysis modality and that zincemia did not reflect the observed low dietary intake of Zn2+.

Associations between bioelectrical impedance parameters and cardiovascular events in chronic dialysis patients

Purpose: Malnutrition and fluid overload contribute to the poor cardiovascular prognosis of dialysis patients. Since bioelectrical impedance analysis is an option for the evaluation of body composition and for the monitoring of hydration state, it may assist in the identification of subjects at high cardiovascular risk. The objective of this study was to evaluate the association between bioelectrical impedance parameters and cardiovascular events. Methods: The association between bioelectrical impedance parameters and fatal and non-fatal cardiovascular outcome was evaluated in 145 dialysis patients. Results: The mean age of the population studied was 54.9 ± 15.4 years, 49.7 % were males, and 35.9 % had diabetes. Forty (27.6 %) patients developed cardiovascular events during the 16 months (8; 32) of follow-up. Comparison of patients with and without cardiovascular events revealed higher extracellular mass/body cell mass (ECM/BCM) and extracellular water/total body water ratios and higher C-reactive protein levels in the former. Survival analysis showed that an ECM/BCM ratio >1.2 and a phase angle <6° were associated with poor cardiovascular prognosis. Among nondiabetic patients, these parameters and capacitance were independently associated with cardiovascular events, suggesting that poor nutritional status and fluid overload are associated with the occurrence of these events. Conclusions: Phase angle, capacitance and ECM/BCM ratio are valuable parameters for the evaluation of cardiovascular prognosis, supporting the use of bioelectrical impedance for the clinical assessment of dialysis patients. © 2012 Springer Science+Business Media Dordrecht.