[Show abstract][Hide abstract] ABSTRACT: The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes.
Full-text · Article · Oct 2015 · Physiological research / Academia Scientiarum Bohemoslovaca
[Show abstract][Hide abstract] ABSTRACT: Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex, HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50+/-0.45 vs 2.11+/-0.35 micromol/l, P<0.01) and was lower comparing to Group II (P<0.01), SC and EPC also decreased (2816+/-600 vs 2071+/-480 cells/ml resp. 194+/-87 to 125+/-67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05).
No preview · Article · Nov 2014 · Physiological research / Academia Scientiarum Bohemoslovaca
[Show abstract][Hide abstract] ABSTRACT: Early versus later start of dialysis is still a matter of debate. Low-protein diets have been used for many decades to delay dialysis initiation. Protein-restricted diets (0.3-0.6 g protein/kg/day) supplemented with essential amino acids and ketoanalogues (sVLPD) can be offered, in association with pharmacological treatment, to motivated stage 4-5 chronic kidney disease (CKD) patients not having severe comorbid conditions; they probably represent 30-40% of the concerned population. A satisfactory adherence to such dietary prescription is observed in approximately 50% of the patients. While the results of the studies on the effects of this diet on the rate of progression of renal failure remain inconclusive, they are highly significant when initiation of dialysis is the primary outcome. The correction of uremic symptoms allows for initiation of dialysis treatment at a level of residual renal function lower than that usually recommended. Most of the CKD-associated complications of cardiovascular and metabolic origin, which hamper both lifespan and quality of life, are positively influenced by the diet. Lastly, with regular monitoring jointly assumed by physicians and dietitians, nutritional status is well preserved as confirmed by a very low mortality rate and by the absence of detrimental effect on the long-term outcome of patients once renal replacement therapy is initiated. On account of its feasibility, efficacy and safety, sVLPD deserves a place in the management of selected patients to safely delay the time needed for dialysis.
Full-text · Article · Sep 2013 · Seminars in Dialysis
[Show abstract][Hide abstract] ABSTRACT: A high body mass index (BMI) is associated with lower mortality in patients undergoing hemodialysis. Short-term weight gains and losses are also related to lower and higher mortality risk, respectively. The implications of weight gain or loss may, however, differ between obese individuals and their nonobese counterparts.
The Current Management of Secondary Hyperparathyroidism: A Multicenter Observational Study (COSMOS) is an observational study including 6797 European hemodialysis patients recruited between February 2005 and July 2007, with prospective data collection every 6 months for 3 years. Time-dependent Cox proportional hazard regressions assessed the effect of BMI and weight changes on mortality. Analyses were performed after patient stratification according to their starting BMI.
Among 6296 patients with complete data, 1643 died. At study entry, 42% of patients had a normal weight (BMI, 20-25 kg/m(2)), 11% were underweight, 31% were overweight, and 16% were obese (BMI ≥30 kg/m(2)). Weight loss or gain (<1% or >1% of body weight) was strongly associated with higher rates of mortality or survival, respectively. After stratification by BMI categories, this was true in nonobese categories and especially in underweight patients. In obese patients, however, the association between weight loss and mortality was attenuated (hazard ratio, 1.28 [95% confidence interval (CI), 0.74 to 2.14]), and no survival benefit of gaining weight was seen (hazard ratio, 0.98 [95% CI, 0.59 to 1.62]).
Assuming that these weight changes were unintentional, our study brings attention to rapid weight variations as a clinical sign of health monitoring in hemodialysis patients. In addition, a patient's BMI modifies the strength of the association between weight changes with mortality.
Full-text · Article · Sep 2013 · Clinical Journal of the American Society of Nephrology
[Show abstract][Hide abstract] ABSTRACT: Hyperphosphatemia has been associated with higher mortality risk in CKD 5 patients receiving dialysis. Here, we determined the association between the use of single and combined phosphate-binding agents and survival in 6797 patients of the COSMOS study: a 3-year follow-up, multicenter, open-cohort, observational prospective study carried out in 227 dialysis centers from 20 European countries. Patient phosphate-binding agent prescriptions (time-varying) and the case-mix-adjusted facility percentage of phosphate-binding agent prescriptions (instrumental variable) were used as predictors of the relative all-cause and cardiovascular mortality using Cox proportional hazard regression models. Three different multivariate models that included up to 24 variables were used for adjustments. After multivariate analysis, patients prescribed phosphate-binding agents showed a 29 and 22% lower all-cause and cardiovascular mortality risk, respectively. The survival advantage of phosphate-binding agent prescription remained statistically significant after propensity score matching analysis. A decrease of 8% in the relative risk of mortality was found for every 10% increase in the case-mix-adjusted facility prescription of phosphate-binding agents. All single and combined therapies with phosphate-binding agents, except aluminum salts, showed a beneficial association with survival. The findings made in the present association study need to be confirmed by randomized controlled trials to prove the observed beneficial effect of phosphate-binding agents on mortality.Kidney International advance online publication, 3 July 2013; doi:10.1038/ki.2013.185.
Full-text · Article · Jul 2013 · Kidney International
[Show abstract][Hide abstract] ABSTRACT: Introduction and Aims: Renal allograft recipients with thrombophilia are at higher risk for early allograft loss, microvascular occlusion and acute
rejection with major consequences for allograft survival. The aim of the present study was to evaluate the prevalence of prothrombotic
risk factors in patients awaiting renal transplantation and its contribution to patient and transplant outcomes.
Methods: All patients with a history of a thromboembolic event, early or recurrent vascular access thrombosis, family history of thrombosis,
or multiple miscarriages underwent laboratory screening for thrombophilia.
Results: Since the introduction of the screening for hypercoagulable risk factors, 156 candidates for renal transplantation underwent
laboratory evaluation. Eighty-eight patients (56%) exhibited at least one prothrombotic laboratory parameter, besides of isolated
hyperhomocysteinemia, which confirmed a thrombophilic state. Lupus anticoagulant, anticardiolipin and beta-2-glycoprotein
was present in 30%, 18% and 13%, and antithrombin III, protein C and protein S deficiencies in 11%, 8% and 10%, respectively.
Factor V Leiden mutation was present in only one patient and prothrombin gene G20210 mutation was not found. Among the 156
patients, 30 underwent renal transplantation and were followed for a median of 199 days (range, 9 – 418). All patients were
on triple immunosuppressive regimen compromising mycophenolate, tacrolimus and prednisone. Thrombophilia was identified in
16 (53%). Seventeen (57%) received perioperative anticoagulation with unfractionated heparin (9 patients with thrombophilia
and 8 without laboratory confirmed thrombophilia). Five (30%) of these patients developed perinephric hematomas. Three patients
with thrombophilia developed thrombotic complications (2 upper limbs deep-vein thrombosis and 1 allograft artery thrombosis)
and 1 patient without thrombophilia developed allograft vein thrombosis, p=0.35. Nine patients developed acute rejection (5 in the group with thrombophilia and 4 in the group without thrombophilia,
p=0.87). Mean glomerular filtration rate was similar between thrombophilic and non-thrombophilic patients in the last follow-up
(54±27 vs. 47±22 mL/min/1.73m², p=0.35). One graft loss and 1 patient death were observed in each group.
Conclusions: Prothrombotic risk factors, especially antiphospholipid antibodies, are highly prevalent in patients awaiting renal transplantation
with a clinical or familial history suggestive of thrombophilia, including early and recurrent vascular access failure. Despite
pre-transplant screening and perioperative treatment and/or monitoring, thrombotic and bleeding complications are still frequent
Full-text · Article · May 2013 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Background
Chronic kidney disease-mineral and bone disorders (CKD-MBD) are important complications of CKD5D patients that are associated with mortality.MethodsCOSMOS is a multicentre, open cohort, prospective, observational 3-year study carried out in haemodialysis patients from 20 European countries during 2005-07. The present article describes the main characteristics of the European dialysis population, the current practice for the prevention, diagnosis and treatment of secondary hyperparathyroidism and the differences across different European regions.ResultsThe haemodialysis population in Europe is an aged population (mean age 64.8 ± 14.2 years) with a high prevalence of diabetes (29.5%) and cardiovascular disease (76.0%), and 28.7% of patients have been on haemodialysis more than 5 years. Patients from the former Eastern countries are younger (59.3 ± 14.3 versus 66.0 ± 13.9), having a lower proportion of diabetics (24.1 versus 30.7%). There were relevant differences in the frequency of measurement of the main CKD-MBD biochemical parameters [Ca, P and parathyroid hormone (PTH)] and the Eastern countries showed a poorer control of these biochemical parameters (K/DOQI and K/DIGO targets). Overall, 48.0% of the haemodialysis patients received active vitamin D treatment. Calcitriol use doubled that of alfacalcidiol in the Mediterranean countries, whereas the opposite was found in the non-Mediterranean countries. The criteria followed to perform parathyroidectomy were different across Europe. In the Mediterranean countries, the level of serum PTH considered to perform parathyroidectomy was higher than in non-Mediterranean countries; as a result, in the latter, more parathyroidectomies were performed in the year previous to inclusion to COSMOS.Conclusions
The COSMOS baseline results show important differences across Europe in the management of CKD-MBD.
Full-text · Article · Nov 2012 · Nephrology Dialysis Transplantation
[Show abstract][Hide abstract] ABSTRACT: Chemical Structure and Molecular Weight Metabolism and Biology Quantification Method Plasma/Serumlevels in Uremic Patients and Healthy Subjects Toxicity and Clinical Relevance Therapeutic Methods to Remove the Toxins References
[Show abstract][Hide abstract] ABSTRACT: Background:
Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine are elevated in patients undergoing kidney transplantation and may contribute to vascular complications. In this study we tested the hypothesis that elevated asymmetric dimethylarginine can be reduced in patients after kidney transplantation by early regular physical exercise. Selected cytokines and metabolic parameters were also analysed.
Plasma samples for analysis of asymmetric dimethylarginine, adiponectin, leptin, soluble leptin receptor, resistin, visfatin, CRP, TNFα and selected metabolic parameters were obtained from randomly selected sixty eight patients after kidney transplantation who agreed to participate in a supervised aerobic exercise program for six months. Samples were collected before the training began (one month after surgery with stabilized graft function) and at six months after initiation. Sixty transplant patients matched for age, sex, HLA typing, duration of previous dialysis, history of cardiovascular disease and immunosupression regimen who did not exercise regularly and did not participate in the training program were examined as controls.
There were no differences in elevated asymmetric dimethylarginine levels between both groups before the training program began. After six months of exercise, asymmetric dimethylarginine concentration in the exercising group I significantly decreased (3.5 ± 0.45 vs 2.11 ± 0.35 µmol/L, P < 0.01) and was also significantly lower comparing to non-exercising group II (2.11 ± 0.23 vs 3.25 ± 0.34 µmol/L, P < 0.01). We found significant changes in exercising group I: adiponectin (15.4 ± 6.6 vs 22.3 ± 6.2 mg/mL, P < 0.01), leptin (51.3 ± 11.2 vs 20.3 ± 9.2 ng/L, P < 0.01), soluble leptin receptor (24.6 ± 8.4 vs 46.1 ± 11.4 U/mL, P < 0.01), resistin (20.8 ± 10.1 vs 14.6 ± 6.4 mg/mL, P < 0.025) and visfatin (1.8 ± 0.2 vs 1.2 ± 0.01 ng/mL, P < 0.05). Blood lipids, HbA1c, CRP and TNFα were also affected by the training program.
Elevated asymmetric dimethylarginine level, selected adipocytokines and proinflammatory cytokines in patients after kidney transplantation were significantly influenced by early regular exercise. This regimen may decrease cardiovascular risk in patients after kidney transplantation.
No preview · Article · Sep 2012 · Vnitr̆ní lékar̆ství
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is increasingly common, and there is an increasing awareness that every strategy should be used to avoid complications of CKD. Restriction of dietary protein intake has been a relevant part of the management of CKD for more than 100 years, but even today, the principal goal of protein-restricted regimens is to decrease the accumulation of nitrogen waste products, hydrogen ions, phosphates, and inorganic ions while maintaining an adequate nutritional status to avoid secondary problems such as metabolic acidosis, bone disease, and insulin resistance, as well as proteinuria and deterioration of renal function. This supplement focuses on recent experimental and clinical findings related to an optimized dietary management of predialysis, dialysis, and transplanted patients as an important aspect of patient care. Nutritional treatment strategies are linked toward ameliorating metabolic and endocrine disturbances, improving/maintaining nutritional status, as well as delaying the renal replacement initiation and improving outcomes in CKD patients. A final consensus states that dietary manipulations should be considered as one of the main approaches in the management program of CKD patients and that a reasonable number of patients with moderate or severe CKD benefit from dietary protein/phosphorus restriction.
No preview · Article · Mar 2012 · Journal of Renal Nutrition
[Show abstract][Hide abstract] ABSTRACT: Introduction: Matrix-metalloproteinases (MMPs) play an important role in cardiovascular (CV) disease. Changes in the serum levels of MMPs have been reported in both dialysis patients and renal transplant recipients, most often in matrix-metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively), and pregnancy-associated plasma protein A (PAPP-A). The aim of our study was to determine whether the changes in serum MMP levels, as documented in patients scheduled for renal transplantation (RTx) and at one year post-RTx, are affected by the type of dialysis treatment and its duration. Methods: The serum levels of MMP-2, MMP-9, PAPP-A were determined prior to RTx and at 12 months post RTx in 239 patients [172 men, 67 women, age 53 (22-80) years]. A control group was made up by 22 healthy individuals [10 men, 12 women, age 51 (22-76) years]. Serum MMP levels were determined using ELISA. Our definition of subclinical atherosclerosis used the Belcaro score as measured by carotid ultrasound. Glomerular filtration rate (GFR; ml/min/1,73 m2) was measured as creatinine clearance and MDRD. Results: Serum PAPP-A levels prior to RTx (time 0) were increased as compared with controls (p < 0.001). An effect of the type of dialysis was most pronounced particularly prior to RTx, with CAPD patients showing higher MMP-2 compared with HD-treated patients (332.7 ± 108 vs 234 ± 49.2 ng/ml; p < 0.05). By contrast, PAPP-A levels in CAPD patients were lower than in HD-treated patients (13.2 ± 4.9 vs. 21.4 ± 10.3; p < 0.001). Dialysis duration shows a significant correlation with pre-RTx PAPP-A levels (r = 0.310; p < 0.01). Pre-RTx serum levels of MMP-9 were comparable with those of controls, to be significantly increased at one year post-RTx (p < 0.001). The increased levels of MMP-9 at one-year post-RTx correlated significantly with graft function determined as MDRD (r = 0.3102; p < 0.01). Conclusion: An effect of the type of dialysis was particularly most pronounced before Rtx, with CAPD -treated patients found to have higher MMP-2 levels compared with HD-treated patients. By contrast, PAPP-A levels in CAPD patients were lower compared with HD-treated patients. Dialysis duration correlated with pre-RTx PAPP-A levels. A new finding is the correlation of increased MMP-9 levels at one year post-RTx with renal function determined as MDRD.
No preview · Article · Jan 2012 · Aktuality v Nefrologii
[Show abstract][Hide abstract] ABSTRACT: Introduction: A role in cardiovascular (CV) disease is played by soluble receptor for advanced glycation end products (sRAGE) and matrix metalloproteinases (MMPs). They belong to a group of non-traditional CV risk markers, and are also determined renal transplantation (RT). Matrix metalloproteinase PAPP-A (pregnancy associated plasma protein-A) and s-RAGE levels are elevated prior to RL to start declining after RT. Literary data about the serum levels of matrix metalloproteinases 2 and 9 (MMP-2and MMP-9) after RT are scanty. Aim: To determine the temporal sequence of changes in serum sRAGE and MMP levels over a one-year period post-RT, and to determine whether they correlate with preclinical atherosclerosis. Methods: Preclinical atherosclerosis was defined as a Belcaro score measured by carotid ultrasound. Serum MMP-2, MMP-9, PAPP-A, and sRAGE levels were determined before RT and at 3, 6, and 12 months post-RT in 142 patients (98 males, 44 females, age 48.7 [range, 22-76] years). A control group included 22 healthy individuals (10 males, 12 females, age 51.0 [range, 22-76] years). Serum MMP and sRAGE levels were determined using ELISA. Results: The serum levels of MMP-2 were lower compared with controls before RT (p < 0.05) and continued to decline after RT. By contrast. MMP-9 in patients awaiting RT was comparable to controls, rising after RT to be significantly increased at one year post-RT: median 602 vs 355ng/ml; p < 0.01. The increased levels of MMP-9 in the late post-RT period correlated significantly with preclinical atherosclerosis (p < 0.01). Serum sRAGE levels were elevated prior to RT to start decreasing after RT as graft function developed. When comparing subgroups with severe (Belcaro score > 2) and mild preclinical atherosclerosis (Belcaro score < 2), sRAGE levels were significantly decreased with severe-clinical atherosclerosis. Conclusion: Decreased sRAGE levels affording inadequate protection to patients exposed to the toxic action of advanced glycation end products can be regarded as a biomarker of CV risk in patients with advanced preclinical atherosclerosis. A novel finding is the increase in MMP-9 in the late post-RT period, correlating significantly with preclinical atherosclerosis and potentially serving as a marker of acute CV risk.
No preview · Article · Jan 2011 · Aktuality v Nefrologii