Arterial stiffness: hemodialysis versus hemodiafiltration.

BACKGROUND AND AIMS: Arterial stiffness seems to be influenced by the dialysis method, but studies are sparse and the results discordant. High substitution volume online hemodiafiltration appears to have beneficial cardiovascular effects in dialysis patients, but its effects on arterial stiffness are not investigated. We aimed to analyze arterial stiffness parameters in high substitution volume post-dilution online hemodiafiltration and compare results to high-flux hemodialysis. METHODS: We studied arterial stiffness parameters using the oscillometric method (Arteriograph IrDA, TensioMed, Budapest, Hungary) in 23 non-diabetic patients on high substitution volume online postdilution hemodiafiltration and 23 non-diabetic patients on high-flux hemodialysis. Dialysis vintage was at least 6 months in all subjects. RESULTS: Hemodiafiltration-treated patients showed a more favorable arterial stiffness profile. Pulse wave velocity was significantly higher in hemodialysis compared to hemodiafiltration patients (10.39±2.29 m/s vs 9.0±1.7 m/s, p=0.026). Augmentation indexes and the diastolic reflection area were also significantly elevated hemodialysis patients compared to hemodiafiltration patients. CONCLUSIONS: High substitution volume online postdilution hemodiafiltration could have a beneficial effect on arterial stiffness and should be assessed in properly sized controlled trials.

Osteoprotegerin and uremic osteoporosis in chronic hemodialysis patients.

INTRODUCTION: Osteoprotegerin (OPG) is a powerful inhibitor of osteoclast activity, and it plays an important role in bone metabolism. In hemodialysis (HD) patients, the relationship between OPG and bone mineral density (BMD) is important, but remains unclear yet. The study objective was to assess the OPG role related to uremic osteoporosis in HD patients. METHODS: This cross-sectional study has been realized on a cohort of 63 chronic HD patients. INCLUSION CRITERIA: elderly prevalent HD patients with an age over 55 years old. EXCLUSION CRITERIA: previous bone disease or previous renal transplant; neoplasia; parathyroidectomy, hormone replacement therapy. The data regarding demographical and clinical characteristics, including treatments for mineral and cardiovascular complications, were recorded. Serum OPG and mineral markers levels were measured. BMD was assessed by calcaneus quantitative ultrasound; it measured broadband ultrasound attenuation, speed of sound (SOS) and stiffness index (STI). RESULTS: The high OPG levels were associated with higher bone mineral density (OPG-SOS P = 0.003; R = 0.37; OPG-STI P = 0.03; R = 0.28). Malnutrition, anemia and advanced age correlated with bone demineralization. Males had higher bone density parameters than females. In patients treated with vitamin D (P = 0.005), the BMD was increased comparing to patients without these treatments. CONCLUSIONS: OPG levels had directly correlated with bone mineral density parameters. Our study further confirms the critical role of OPG in the pathogenesis of uremic osteoporosis in ESRD. Whether the increased circulant OPG protect against bone loss in patients undergoing HD remains to be established.

Mineral and bone disorders, morbidity and mortality in end-stage renal failure patients on chronic dialysis.

BACKGROUND AND AIM: In spite of numerous interventions, the control of mineral disturbances remains poor in end-stage renal failure (ESRF) patients. Chronic kidney disease - mineral and bone disorders (CKD-MBD) represent an important cause of mortality and morbidity. The aim of this study is to analyze the relationship between mineral and bone disorders (MBD) and their components impact on all-cause mortality and cardiovascular (CDV) mortality and morbidity in chronic dialysis patients. METHODS: This prospective study was carried out in a cohort of 92 randomly selected patients with ESRF treated with hemodialysis (HD) and peritoneal dialysis (PD). The data regarding demographic and clinical characteristics were recorded, including vascular disease (coronary, cerebral, peripheral). The follow-up lasted 40 months and the final evaluation included the number and causes of deaths, CDV events and disease. Serum Ca, P, ALP, iPTH, albumin, cholesterol, urea and creatinine levels were measured. The plain radiographic films of hands and pelvis evaluated all bone abnormalities suggestive of renal osteodystrophy (ROD) and peripheral vascular calcification (VC). RESULTS: All-cause annual mortality represented 9.25% in HD and 9.09% in PD patients. The CDV mortality represented almost 44% in HD patients and 66% in PD patients from all deaths. There was a high prevalence of CDV diseases and events. High and low serum P levels were associated with a worse survival rate. Hypercalcaemia was associated with high risk for CDV events in HD patients. In PD patients, the relationship between increased ALP levels and all-cause mortality was significant. Other mineral markers were not predictive of the outcome in the studied patients. In the HD patients the severity of VC was associated with all-cause and CDV mortality, and with CDV events. Male gender, hypercholesterolemia, decreased URR, albumin and creatinine were identified as risk factors for all-cause mortality. The diabetics had higher death rates. Low dialysis efficacy represented a risk factor for mortality and CDV diseases and events. In PD patients, low albumin induced a higher death rate. In PD patients the death rate was similar to HD patients. CONCLUSION: All-cause mortality was higher than in general population, but lower than the chronic dialysis patients' mortality reported in other studies. The death rates in HD and PD patients were similar. VC and serum P levels influenced the outcome in the HD patients - increased the risk for all-cause and CDV mortality, but also for CDV events. ALP levels influenced outcome in PD patients. There were no significant differences between HD and PD patients regarding outcome.

Survival after parathyroidectomy in chronic hemodialysis patients with severe secondary hyperparathyroidism.

INTRODUCTION: The life for end-stage renal disease patients has remarkably improved in the last years. Although mineral and bone disorders remain as unsolved complication, in severe secondary hyperparathyroidism (sHPT), the ultimate treatment is parathyroidectomy (PTX). It is an old treatment, but there are still insufficient data regarding survival after PTX. The study goals were to compare 2-year mortality and morbidity after PTX in surgically versus medically treated sHPT and to compare the efficacy and safety in subtotal versus total PTX in a cohort of patients receiving hemodialysis (HD). METHODS: This prospective, longitudinal study was carried out on a cohort of chronic HD patients with severe sHPT (iPTH over 700 pg/ml). Among the overall HD population, 26 patients underwent PTX. This group was compared to a control group treated with specific drugs. Laboratory parameters, specific symptoms and mortality were registered after 24 months of follow-up for each group. The subgroups of subtotal and total PTX patients were also compared. RESULTS: All average values of mineral markers were significantly reduced after PTX, as a proof that surgical treatment was effective. The reduction in mineral markers and the improvement in symptoms and mortality rates were similar after total and subtotal PTX. Bone pain was significantly lower in patients after PTX than in those drug treated (p = 0.0005), but not muscle weakness and itching. Survival at 2 years was better in patients surgically treated (PTX) despite significantly higher mean baseline values of iPTH, Ca and ALP compared to patients medically treated (p = 0.03). CONCLUSIONS: We compared clinical and laboratory outcomes in HD patients with severe sHPT. Mortality, bone pain and mineral markers were improved by PTX. Total and subtotal PTX had similar clinical outcomes.

DNA methylation: hemodialysis versus hemodiafiltration.

Aberrant DNA methylation is an emerging characteristic of chronic kidney disease including dialysis patients. It appears to be associated to inflammation. We compared the global DNA methylation status in 10 control subjects compared to 80 dialysis patients (N = 40 on-line hemodiafiltration, N = 40 high-flux hemodialysis) in relation to the dialysis technique and inflammation. Whole blood DNA methylation was assessed with a 5-mc DNA enzyme linked immunosorbent assay Kit. Global DNA methylation was higher in hemodialysis (HD) compared to on-line hemodiafiltration (HDF) patients (0.045 vs. 0.039; P < 0.0001) and controls (0.045 vs. 0.0284; P = 0.0002 for HD; 0.039 vs. 0.0284; P = 0.0254 for on-line HDF). To study the influence of the dialysis technique on DNA methylation we divided dialysis patients according to the median value of 5-mC. DNA methylation was highest in inflamed patients on hemodialysis. The dialysis technique was the only independent predictor of global DNA methylation in dialysis patients. On-line HDF could be associated with a favorable DNA methylation profile.

FGF-23, vascular calcification, and cardiovascular diseases in chronic hemodialysis patients.

INTRODUCTION: Chronic hemodialysis (HD) patients have bad prognosis and cardiovascular diseases (CVD) represent their main threatening complication. Fibroblast growth factor (FGF-23) has been associated with all kinds of evil consequences, including cardiovascular morbidity, but some studies demonstrated the contrary. Therefore, it is important to know whether FGF-23 is associated with cardiovascular risk or protection. The purpose of this study was to assess the links between FGF-23 and intimal vascular calcification (VC) and with the presence of CVD in chronic HD patients. PATIENTS AND METHODS: This study was carried out on a cohort of randomly selected 88 prevalent HD patients. We recorded demographical, clinical, and biochemical data, including FGF-23. VC was evaluated on carotid ultrasound. CVD were registered. RESULTS: The mean age was 59.68 ± 14.49 years, HD vintage was 59.61 ± 52.39 months, and 20 patients were diabetic (22.72 %). VC was present in 54 patients (61.4 %) and 25 patients (28.4 %) had CVD. FGF-23 correlated positively with HD vintage (r = 0.37; p < 0.001) and iPTH (r = 0.21; p = 0.048). FGF-23 did not correlate with VC score. Patients with CVD were older (p = 0.006), had lower FGF-23 (p = 0.008), higher VC score (p = 0.009), lower Hb (p = 0.008), albumin (p = 0.003), and creatinine (p = 0.03). Low FGF-23 was identified as a risk factor for CVD. CONCLUSION: We report on a novel association between low FGF23 and CVD in chronic HD patients and a lack of correlation of FGF-23 with VC. FGF-23 could play a role in cardiovascular protection that remains to be confirmed in larger studies.

The influence of vitamin E supplementation on erythropoietin responsiveness in chronic hemodialysis patients with low levels of erythrocyte superoxide dismutase.

About 12-15 % of hemodialysis patients have a poor response to recombinant human erythropoietin (rHuEPO). The aim of this prospective study was to examine the influence of oxidative stress and vitamin E supplementation on rHuEPO responsiveness in chronic hemodialysis patients. Sixty-five hemodialysis patients treated with rHuEPO were studied. Those with iron deficiency, blood loss, malignancy, vitamin B12 and folate deficiency, severe hyperparathyroidism, liver cirrhosis, and congestive heart failure were excluded. Twenty-one healthy volunteers served as a control group. Malondialdehyde, carbonyl proteins, erythrocyte superoxide dismutase (SOD), ceruloplasmin, and serum antioxidant capacity were measured. Values of SOD > 150 U/ml were considered as normal. Patients with SOD < 150 U/ml were divided in two groups: group A (n = 11): treated with vitamin E 400 mg/day (600 IU/day) for 8 weeks; group B (n = 13): not treated. A third, group C consisted of patients with normal SOD. rHuEPO doses (U/kg/week) were recorded. rHuEPO responsiveness index was calculated as rHuEPO U/week/hematocrit. A poor response was defined as a rHuEPO responsiveness index >200. SOD positively correlated with hemoglobin (p = 0.0018, R = 0.337) and negatively with rHuEPO responsiveness index (p = 0.0122, R = 0.319). Vitamin E-treated patients from group A exhibited significantly increased hemoglobin levels as compared to initial values (10.5 ± 0.3 vs. 8.6±0.4, p = 0.002). In comparison with group B, the vitamin E-treated patients displayed a higher hemoglobin (10.5 ± 0.3 vs. 9.4 ± 0.3, p = 0.04), had a lower rHuEPO dose (85.7 ± 7.4 vs. 136.8 ± 13.8, p = 0.025), and a significantly improved rHuEPO responsiveness (rHuEPO responsiveness index 177.9 ± 28.6 vs. 314.1 ± 34.0, p = 0.006). Patients from group A significantly improved their rHuEPO responsiveness after vitamin E therapy as compared to baseline (rHuEPO responsiveness index 177.9 ± 28.6 vs. 271.7 ± 30.3, p = 0.034). We conclude that lower values of SOD correlate with lower hemoglobin, higher rHuEPO dose and poor response to rHuEPO in chronic hemodialysis patients. Vitamin E supplementation significantly improves rHuEPO responsiveness, increases hemoglobin level, and decreases rHuEPO dose.

High-tone external muscle stimulation in endstage renal disease: effects on quality of life in patients with peripheral neuropathy.

OBJECTIVE: High-tone external muscle stimulation (HTEMS) has been shown to ameliorate painful peripheral neuropathy of dialysis patients. We hypothesized that HTEMS could also lead to improved parameters of health-related quality of life (HRQOL). METHODS: 25 end-stage renal disease (ESRD) patients (17 men/8 women, mean age 62.2 ± 14.2 years) were enrolled for the study. For evaluation of HRQOL the short form SF-36 was used. In addition, the Hospital Anxiety and Depression Scale (HADS) and the pain severity score were investigated. HTEMS was applied intradialytically for 1 hour, 3 times a week. Its effect was evaluated just before the beginning and both 6 and 12 weeks after onset of this study. RESULTS: SF-36 showed a significant effect of time for the subscales of physical role functioning and social functioning. A marginal significant positive trend could be observed for physical functioning. The pain symptom questionnaire sum scores improved significantly after 12 weeks. The HADS did not change significantly. CONCLUSION: The data indicate that intradialytic HTEMS treatment of ESRD patients with peripheral neuropathy ameliorates various components of physical health.

Variation of clinical and laboratory features in chronic dialysis patients treated with high-flux hemodialysis after switching to online hemodiafiltration.

PURPOSE: The study of online hemodiafiltration (HDF) benefits over high-flux hemodialysis (HD) raises great interest. The purpose was to compare clinical and laboratory parameters in patients treated with HD who were switched to HDF. METHODS: Forty-eight HD patients (study group) were switched to HDF, while other 521 patients remained on HD as a control group. During last 6 HD months and during first year of HDF, we determined in both groups the following parameters: monthly-weekly dialysis time, systolic and diastolic blood pressure, body mass index (BMI), interdialytic body weight gain (IBWG), blood flow rate (Qb), weekly erythropoietin-stimulating agents dose (EPO), single-pool Kt/V, calcium, phosphorus (P), hemoglobin and normalized protein catabolic ration (nPCR), plus every 3 months--albumin, parathormone (PTH), ferritin and transferrin saturation (TSAT). In both groups, parameters in the last 6 HD months were compared to those in the first 6 months and, respectively, to those in the first year of HDF. RESULTS: In the study group, albumin and nPCR were significantly higher in the HD period not only compared to the first 6 months of HDF, but also compared to the first year of HDF. IBWG and P were higher with HD compared to the first year of HDF, but not with the first 6 months. PTH, Kt/V, Qb and EPO were higher in both HDF periods. In the control group, albumin was significantly higher in the first 6 months after the switch, but it was significantly lower in the first year. BMI, ferritin, PTH, Kt/V, Qb, TSAT and weekly dialysis time were higher in both HDF periods, while nPCR, EPO, SBP and DBP were lower. IBWG and Hb rose only during the first year after the switch, while P was lower in the first year, but not in the first 6 months. CONCLUSIONS: Nutrition, assessed by albumin, nPCR and BMI, was not improved by HDF compared to HD. With HDF, Kt/V and phosphorus control were better, similar results were observed in the control group. A larger EPO dose was needed with HDF for maintaining a similar hemoglobin level.

276G>T Polymorphism of the ADIPOQ Gene Influences Plasma Adiponectin in Type 2 Diabetes Patients but Is Not Predictive for Presence of Type 2 Diabetes in a Caucasian Cohort from Romania.

BACKGROUND: Previous reports associated ADIPOQ 276G>T polymorphism with plasma adiponectin levels and diabetes. Our objective was to study this polymorphism in type 2 diabetes (T2D) Romanian patients and to assess its influence on plasma adiponectin levels; possible link to prevalence of T2D was also addressed. DESIGN: Case control studyMaterial and Methods: Consecutive T2D patients, age and sex matched controls were genotyped for the 276 ADIPOQ locus. Medical history, laboratory evaluation, plasma adiponectin were assessed. OUTCOMES: 105 T2D patients and 48 controls were included. Adiponectin was higher in controls (17.04±3.02 µg/ml) than in T2D patients (10.32±1.16 µg/ml), difference failed to reach significance (p=0.06). Genotype distribution wasn't different between T2D patients and controls. 44 (41.90%) of T2D patients had GG genotype, 51 (48.57%) GT and 10 (9.52%) TT genotype. Adiponectin was higher (19.03±3.46 µg/ml) in diabetic TT allele carriers than in GT (9.96±1.76 µg/ml) or GG patients (8.71±1.60 µg/ml) p=0.003. In controls, 28 (58.33 %) subjects were carriers of the GG genotype, 16 (33.33%) had GT genotype and 4 (8.33%) had TT genotype. There weren't significant differences in the studied parameters between different genotypes in the control group. Logistic regression disclosed age p=0.0001 (OR 1.086; CI 1.041/1.133), waist circumference p=0.00049 (OR 1.084; CI 1.036/1.135), adiponectinemia p=0.036 (OR 0.963; CI 0.929/0.998) but not genotype as predictors for the presence of diabetes. CONCLUSION: Presence of the TT allele at the 276 locus of the ADIPOQ gene is associated with higher plasma adiponectin levels in type 2 diabetes patients. Plasma adiponectin, and not genotype at the 276 locus is predictive for the presence of T2D.

Intercellular adhesion molecule, plasma adiponectin and albuminuria in type 2 diabetic patients.

AIMS: Our study addressed the influence of early inflammatory stages of diabetic kidney disease: leukocyte adhesion and monocyte activation (as assessed by intercellular leukocyte adhesion molecule-ICAM-1 and monocyte chemoatractant protein-MCP-1) on the degree of albuminuria. Plasma levels of adiponectin, a possible anti-inflammatory counteracting mechanism, were also studied in correlation to the above-mentioned cytokines. METHODS: 79 consecutive type 2 diabetic outpatients and 46 controls were included. Routine laboratory analysis, urinary albumin to creatinine ratio (uACR), plasma adiponectin, plasma ICAM-1 and urinary MPC-1 were assessed. RESULTS: In multiple regression ICAM-1 (p=0.004) and adiponectin (p=0.04) were the main determinants of uACR. Plasma adiponectin positively correlated to ICAM-1 (p=0.03, r=0.24). In albuminuric patients (uACR ≥30 mg/g) plasma adiponectin was significantly higher compared to normoalbuminuric ones (uACR <30 mg/g). In albuminuric patients the main determinants of uACR were plasma ICAM-1 and adiponectin. In multiple regression ICAM-1 is the only one that retains statistical significance (p=0.02). Urinary MCP-1 did not correlate to uACR. CONCLUSIONS: In our type 2 diabetic patients, plasma levels of ICAM-1 and adiponectin are predictive for albuminuria. Urinary MCP-1 does not correlated to uACR. Plasma adiponectin positively correlates to adhesion molecule ICAM-1 in our cohort.

Vascular calcifications and renal osteodystrophy in chronic hemodialysis patients: what is the relationship between them?

INTRODUCTION: Vascular calcifications (VCs) and renal osteodystrophy (ROD) are frequently seen together and represent the major causes of morbidity and mortality in hemodialysis (HD) patients. Some studies suggest a pathogenic link between them, but there is no consensus as yet regarding this issue. The main objective of our study was to establish whether there is any relation between VCs and ROD in our HD patients. We evaluated the prevalence of VCs and ROD and the relationship between VCs and some clinical and biochemical characteristics of HD patients. METHODS: We examined radiological signs of VCs and ROD on hands and pelvis bone radiographs in 81 chronic HD patients, and we calculated a VC score on this basis. RESULTS: We found a significant relation between radiological signs of ROD and those of VC (P = 0.019). The patients with ROD had a higher mean VC score (P = 0.02). By linear regression, the VC score correlated directly with serum calcium (Ca), phosphorus (P), intact parathyroid hormone (iPTH) and CaxP product and inversely with serum albumin. The logistic regression model revealed that ROD, male gender and treatment with calcium salts were predictive of VCs development. There were no associations between VCs and age, HD vintage, diabetes, dialysate Ca concentration, vitamin D treatment, spKt/V, URR and C-reactive protein (CRP) levels. CONCLUSION: There seems to be a pathogenetic link between bone and artery diseases in chronic HD patients. Both VCs and ROD have a high prevalence. ROD, male gender and treatment with calcium salts are risk factors for VCs.

Once-every-2-weeks and once-weekly epoetin beta regimens: equivalency in hemodialyzed patients.

BACKGROUND: Currently, less frequent than once-weekly subcutaneous epoetin administration regimens were shown to be equally effective and safe as once-weekly schedules in stable predialysis and peritoneal dialysis patients. Bioequivalency of once-every-2-weeks and once-weekly subcutaneous administration of the same total dose of epoetin beta for the maintenance phase of anemia treatment in stable iron-replete long-term hemodialysis patients therefore was investigated prospectively. METHODS: Two hundred seven stable selected hemodialysis patients without diabetes, acute illness, significant inflammation, malnutrition or hyperparathyroidism administered once-weekly subcutaneous epoetin beta and preserving stable hemoglobin levels between 10 and 12 g/dL (100 and 120 g/L; difference between maximum and minimum of 3 subsequent levels

The success story of peritoneal dialysis in Romania: analysis of differences in mortality by dialysis modality and influence of risk factors in a national cohort.

BACKGROUND: This report describes the status of renal replacement therapy (RRT), particularly continuous ambulatory peritoneal dialysis (CAPD), in Romania (a country with previously limited facilities), outlines the fast development rate of CAPD, and presents national changes in a European context. METHODS: Trends in the development of RRT were analyzed in 2003 on a national basis using annual center questionnaires from 1995 to 2003. Survival data and prognostic risk factors were calculated retrospectively from a representative sample of 2284 patients starting RRT between 1 January 1995 and 31 December 2001 (44% of the total RRT population investigated). RESULTS: The annual rate of increase in the number of RRT patients (11%) was supported mainly by an exponential development of the CAPD population (+600%); the hemodialysis (HD) growth rate was stable (+33%) and renal transplantation had a marginal contribution. The characteristics of both HD and PD incident patients changed according to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). There were significant differences between PD and HD incident populations, PD patients being significantly older and having a higher prevalence of diabetic nephropathy and baseline comorbidities, probably reflecting different inclusion policies. The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4 - 91.8] and 62.2% at 5 years (CI 59.4 - 65.0). The initial treatment modality did not significantly influence patients' survival. There was no difference in unadjusted technique survival during the first 2 years; afterwards, there was a clear advantage for HD, with more patients being transferred from PD to HD. Several factors seemed to significantly and negatively influence PD patients' survival (Cox regression analysis): male gender, lack of predialysis erythropoietin treatment, and initial comorbidities. Stratified analysis to discover the influence of these factors on patients' survival revealed that HD was associated with an increased risk of death in the younger nondiabetic end-stage renal disease population, regardless of other coexisting comorbid conditions. However, in older patients (>65 years) and in diabetics, regardless of the presence or absence of associated comorbid conditions, there was no significant difference in death rates between HD and PD patients. CONCLUSIONS: We report an impressive quantitative and qualitative development of CAPD in one of the rapidly growing Central and Eastern Europe countries. CAPD should be the method of choice for young nondiabetic end-stage renal disease patients. Improvement in predialysis nephrologic care and in transplantation rates is required to further ensure the ultimate success of the Romanian PD program.