Hemodialyzed Research Articles

Outbreak of Ralstonia spp. and Burkholderia spp. Catheter-Related Bloodstream Infection in Hemodialysis Unit

The Ralstonia species (RB) and Burkholderia species (BB) are bacteria responsible for nosocomial infections in frail patients such as hemodialyzed (HD) patients. Here, we report how we managed an outbreak caused by RB and BB that occurred in a dialysis unit. From the 7th to the 16th of April 2021, an infection due to RB and BB occurred in 7 out of 39 (17.9%) HD patients with central venous catheter (CVC). Disinfectants, CVC-lock therapy solutions, water by reverse osmosis unit (ROW) and dialysis concentrates were cultured, including the biofilm from the loading plastic tubes (LPTs) that connect the hemodialysis consoles (HCs) to the ROW delivery line. The antibiotic treatment was successful for all patients. RB and BB were isolated in the biofilm of 11/37 LPTs. Three out of 11 positive LPTs were associated with the infected patients. The ROW delivery line was modified to provide a whole disinfection with the HCs connected, avoiding the risk of new contamination of the LPTs. A filtration module of 0.01 mm was added prior to the ROW delivery line. Our experience suggests that outbreaks sustained by unusual bacteria such as RB and BB should be promptly investigated to treat the infected patients with the appropriate therapy and to identify the possible source of infection, making the needful changes to achieve a safer dialysis unit.

Gut microbiota associations with chronic kidney disease: insights into nutritional and inflammatory parameters.

The gut barrier, comprising gut microbiota, plays a pivotal role in chronic kidney disease (CKD) progression and nutritional status. This study aimed to explore gut barrier alterations in hemodialyzed (HD) patients, non-HD (NHD) CKD patients, and healthy volunteers. Our cross-sectional study enrolled 22 HD patients, 11 NHD patients, and 11 healthy volunteers. We evaluated fecal microbiota composition (assessed via bacterial 16S rRNA gene sequencing), fecal IgA levels, surrogate markers of gut permeability, serum cytokines, appetite mediators, nutritional status, physical activity, and quality of life. HD patients exhibited significant alterations in fecal microbiota composition compared to healthy volunteers, with observed shifts in taxa known to be associated with dietary patterns or producing metabolites acting on human host. In comparison to healthy volunteers, individuals with HD patients exhibited elevated levels of inflammatory markers (CRP, IL-6 and TNF-α), glucagon-like peptide-2, and potential anorexigenic markers (including leptin and peptide YY). NHD patients had increased levels of CRP and peptide YY. Overall fecal microbiota composition was associated with height, soft lean mass, resting energy expenditure, handgrip strength, bone mineral content and plasma albumin and TNF-α. Compared to healthy volunteers, HD patients have an altered fecal microbiota composition, a higher systemic inflammation, and a modification in plasma levels of appetite mediators. While some differences align with previous findings, heterogeneity exists likely due to various factors including lifestyle and comorbidities. Despite limitations such as sample size, our study underscores the multifaceted interplay between gut microbiota, physiological markers, and kidney function, warranting further investigation in larger cohorts.

#4562 OUTBREAK OF RALSTONIA SPP AND BURKHOLDERIA SPP CATHETER-RELATED BLOODSTREAM INFECTION IN A HAEMODIALYSIS UNIT

Abstract Background and Aims Ralstonia (RB) and Burkholderia (BB) species are environmental Gram-negative bacilli responsible for several nosocomial infections in immunocompromised or frail patients. RB and BB may contaminate medical devices because of their ability to survive in a biofilm and with low nutrient requests. Reports of infection outbreaks due to RB and BB are very few and only in sporadic cases, the source of contamination was identified. We describe here: i) how we managed an outbreak of bacteremia caused by RB and BB occurred in our dialysis unit, ii) what we have done to identify the source of infection and iii) the countermeasures we adopted to reduce the risk of new events. Method From 7 to 16 April 2021, 6 out of 39 (15.4%) hemodialyzed (HD) patients with a long-term indwelling central venous catheter (CVC) developed symptoms related to infection. Blood cultures revealed the presence of RB and BB. Thus, a prompt check of the blood cultures of all HD patients with CVC was performed. Blood samples were incubated in an automated microbial detection system (VIRTUO BIOMERIEUX) and subsequently, blood positive samples were inoculated in Chocolate and Columbia blood Agar plates. In addition, a microbiological analysis of disinfectants, drugs used in dialysis unit and samples collected from the reverse osmosis water unit (ROW) and from the ROW delivery line were performed. None of the samples obtained from the ROW and from the ROW delivery line resulted positive. Thus, a microbiological analysis of the biofilm attached on the loading pipes (LP) and on the loading plastic tubes (LPT) that connect the hemodialyzer consoles (HC) to the ROW delivery line were performed. Briefly, LTP were subjected to ultrasound sonication at 30-40 KHz (BactoSonic-Bandelin), to disrupt the bacterial biofilm. The material obtained from sonication was cultured. Bacteria was identified by an automated mass spectrometry (MALDI-TOF VITEK®MS, Biomerieux). Results Bacteremia due to RB and BB was confirmed in 7 out of 39 (17.9%) of the hemodialyzed patients with a long-term indwelling CVC. 1 out of 7 was asymptomatic. Baseline characteristics of the 6 symptomatic patients were: mean age 68±16 years; mean C-reactive protein 4.48±1.3 mg/dl; mean procalcitonin 13.27±11.07 ng/ml; mean body temperature 37.9±1.4°C. The antibiotic therapy was decided according to antibiogram and included meropenem and ciprofloxacin. CVC were removed in all infected patients between 6 to 11 days from the diagnosis. Concomitantly, a new one was placed. None of the HD patients with arterio-venous fistulae developed bacteremia. RB and BB were isolated in the biofilm of 11 out of 37 LPT. Thus, we modified the ROW delivery line in order to set up a scheduled chemical and physical disinfections of the ROW delivery line with the hemodialysis consoles connected avoiding the risk of new contamination of the LPT and loading pipes. Briefly, on alternate months the whole system that include ROW delivery line (PE-Xa Medical Device, Fresenius Medical Care), loading pipes, LPT and hemodialysis consoles are disinfected by hot water (90°C) produced by a water heater (AquaB plus HF, Fresenius Medical Care) and by chemical disinfectant, 5% peracetic acid according to the protocols made by the console fabricant. In addition, we added to the reverse osmosis system a filtration module of 0.01 μm (AquaUF, Fresenius Medical Care) prior to the ROW delivery line, Figure 1. Awaiting for the modification of the ROW delivery line, the patients with CVC were dialyzed using a portable water treatment unit. After more than 14 months from the modification of the whole system for production and delivery of ROW none of the hemodialyzed patients developed infection by RB and BB. Conclusion Our experience suggests that infection outbreak by unusual bacteria such as RB and BB could be successful treated using antibiotic therapy. Nevertheless, in dialysis unit the source of infection should be investigated in order to adopt the countermeasures necessary to reduce the risk of new infections.

Durability of Humoral and Cellular Immunity after an Extended Primary Series with Heterologous Inactivated SARS-CoV-2 Prime-Boost and ChAdOx1 nCoV-19 in Dialysis Patients (ICON3).

The durability of a three-dose extended primary series of COVID-9 vaccine in dialysis patients remains unknown. Here, we assessed dynamic changes in SARS-CoV-2-specific humoral and cell-mediated immunity at baseline, 3 months, and 6 months after the extended primary series in 29 hemodialyzed (HD), 28 peritoneal dialyzed (PD) patients, and 14 healthy controls. Participants received two doses of inactivated SARS-CoV-2 vaccine followed by a dose of ChAdOx1 nCoV-19 vaccine. At 6 months, median anti-RBD IgG titers (IQR) significantly declined from baseline in the HD (1741 (1136–3083) BAU/mL vs. 373 (188–607) BAU/mL) and PD (1093 (617–1911) BAU/mL vs. 180 (126–320) BAU/mL) groups, as did the mean percent inhibition of neutralizing antibodies (HD: 96% vs. 81%; PD: 95% vs. 73%) (all p < 0.01). Age and post-vaccination serological response intensity were predictors of early humoral seroprotection loss. In contrast, cell-mediated immunity remained unchanged. In conclusion, humoral immunity declined substantially in dialysis patients, while cell-mediated immunity remained stable 6 months after the extended heterologous primary series of two inactivated SARS-CoV-2/ChAdOx1 nCoV-19 vaccine. A booster dose could be considered in dialysis patients 3 months after this unique regimen, particularly in the elderly or those with a modest initial humoral response.

BALKAN ENDEMIC NEPHROPATHY, PULSE WAVE VELOCITY AND INCREASED TELOMERE LENGTH-ASSOCIATED CARDIOVASCULAR MORTALITY IN PATIENTS UNDERGOING CHRONIC HEMODIALYSIS

Objective: Balkan endemic nephropathy (BEN) is characterized with later onset, milder forms of hypertension and lower pulse wave velocity (PWV)). We hypothesized that telomere length (TL) would be longer in BEN patients and associated with lower PWV and less cardiovascular (CV) mortality. Design and method: On total 124 hemodialysed (HD) patients (68 BEN, 56 non-BEN; 48.4% men; 65 ± 14 years) were enrolled and followed-up for 25 months. Blood pressure and PWV were determined before mid-week dialysis. TL was determined by telomere restriction fragment analysis. Results: Age-sex adjusted TL was significantly longer in the BEN group (7.19 vs 6.79; p &lt; 0.001) despite being significantly older. In the BEN group TL was associated with PWV (beta = -0.373, p &lt; 0.05), and in the non-BEN group with age (beta = -0.680, p &lt; 0.01). In the full-adjusted model of multivariate linear regression analyses significant predictors of TL were systolic BP/PWV, and age in the BEN and the non-BEN group, respectively. BEN patients died significantly less frequently from CV events than non-BEN patients (p &lt; 0.001) and lived significantly longer (log-rank p = 0.04). Patients who died had significantly shorter TL than survivors (p &lt; 0.001). In the Cox Regression analysis older age, diagnosis of non-BEN and shorter TL were determinants of shorter survival in the entire cohort. In the BEN group shorter TL was the only determinant of shorter survival (HR 0.11 [95% CI 0.03, 0.35]). To analyze the diagnostic value of TL for CV mortality we used ROC analysis that revealed TL &lt; 6.21 Kb to be useful for prediction of CV mortality in patients undergoing chronic HD. Conclusions: Shorter TL is associated with CV mortality in patients undergoing chronic HD. BEN patients had longer TL and longer survival than other ESKD patients. PWV was significant predictor of TL in BEN patients. This study confirmed our hypothesis that BEN is associated with slower vascular aging.

Immunogenicity of ChAdOx1 nCoV-19 vaccine after a two-dose inactivated SARS-CoV-2 vaccination of dialysis patients and kidney transplant recipients

Vaccination with inactivated SARS-CoV-2 virus produces suboptimal immune responses among kidney transplant (KT), peritoneal dialyzed (PD), and hemodialyzed (HD) patients. Participants were vaccinated with two-dose inactivated SARS-CoV-2 vaccine (V2) and a third dose of ChAdOx1 nCoV-19 vaccine (V3) at 1–2 months after V2. We enrolled 106 participants: 31 KT, 28 PD, and 31 HD patients and 16 controls. Among KT, PD, and HD groups, median (IQR) of anti-receptor binding domain antibody levels were 1.0 (0.4–26.8), 1092.5 (606.9–1927.2), and 1740.9 (1106–3762.3) BAU/mL, and percent neutralization was 0.9 (0–9.9), 98.8 (95.9–99.5), and 99.4 (98.8–99.7), respectively, at two weeks after V3. Both parameters were significantly increased from V2 across all groups (p < 0.05). Seroconversion and neutralization positivity rates in PD, HD, and control groups were 100% but were impaired in KT patients (39% and 16%, respectively). S1-specific T-cell counts were increased in PD and HD groups (p < 0.05) but not in KT patients. The positive S1-specific T-cell responder rate was > 90% in PD, HD, and control groups, which was higher than that in KT recipients (74%, p < 0.05). The heterologous inactivated virus/ChAdOx1 nCoV-19 vaccination strategy elicited greater immunogenicity among dialysis patients; however, inadequate responses remained among KT recipients (TCTR20210226002).

The Mutual Contribution of 3-NT, IL-18, Albumin, and Phosphate Foreshadows Death of Hemodialyzed Patients in a 2-Year Follow-Up.

Patients with chronic kidney disease (CKD), especially those who are hemodialyzed (HD), are at significantly high risk of contracting cardiovascular disease and having increased mortality. This study aimed to find potential death predictors, the measurement of which may reflect increased mortality in HD patients, and then combine the most promising ones in frames of a simple death risk assessment model. For this purpose, HD patients () with acute myocardial infarction in the last year (HD group) and healthy people (control group) as a comparative group () were included in the study. Various laboratory determinations and non-invasive cardiovascular tests were performed. Next, patients were followed for two years, and data on cardiovascular (CV) deaths were collected. On this basis, two HD groups were formed: patients who survived (HD-A, ) and patients who died (HD-D, ). To model HD mortality, 21 out of 90 potential variables collected or calculated from the raw data were selected. The best explanatory power (95.5%) was reached by a general linear model with four variables: interleukin 18, 3-nitrotyrosine, albumin, and phosphate. The interplay between immuno-inflammatory processes, nitrosative and oxidative stress, malnutrition, and calcium-phosphate disorders has been indicated to be essential in predicting CV-related mortality in studied HD patients. ClinicalTrials.gov Identifier: NCT05214872.

Analysis of Experiences in Preventing COVID-19 in Hemodialysis Centers of the North of Poland before the Era of Vaccination.

Background: The appearance of very contagious SARS-CoV-2 variants and waning vaccine immunity may indicate the need to return to using universal methods of preventing the spread of COVID-19. Methods: We performed a multicenter retrospective cohort survey study to describe the methods used in dialysis units to prevent and control the spread of SARS-CoV-2 and also the association between these methods and the incidence of COVID-19 among hemodialyzed (HD) patients before the era of vaccination. The study population included all maintenance HD patients (n = 1569) in 14 dialysis units in the Pomeranian Voivodeship. Results: The group of 352 patients (199 men, 153 female) were confirmed for COVID-19. The absolute cumulative incidence in the studied period was 22.4%. It varied widely by dialysis units, ranging from 9.4% to 36.9%. Universal preventive methods were applied by all units. Different additional methods were implemented in some stations with varying frequency (36–86%). In order to quantify the scale of the applied additional preventive methods, we calculated a summary prevention index (PI), i.e., one point for one additional method. Lower incidence was found in centers applying dialysis in isolation of patients hospitalized due to diseases requiring hospitalization (17.42% ± 6.89 vs. 26.54 ± 6.34; p = 0.028) and higher incidence in medium-size dialysis centers (ANOVA F: p = 0.017). Significant inverse correlation between PI and incidence was demonstrated as well (r = −0.759; p = 0.002). Conclusions: The higher the number of implemented preventive measures, the lower the risk of COVID-19 infection in HD patients. Among applied procedures the isolation of hospitalized patients is of significant importance. The measures proved to be effective in prevention before the vaccination era should be continued, as the threat of SARS-CoV-2 still exists.

Analytical evaluation of the Nittobo Medical tartrate resistant acid phosphatase isoform 5b (TRACP-5b) EIA and comparison with IDS iSYS in different clinically defined populations.

Tartrate-resistant acid phosphatase, isoform 5b (TRACP-5b) is a bone resorption marker not influenced by renal function or food intake. TRACP-5b can be measured with Nittobo Medical enzymatic-immunoassay and IDS-iSYS automated immunoassay. We evaluated the Nittobo assay and established reference ranges for a Western-European population. We compared Nittobo and IDS results in different well-defined clinical populations. We established the limits of detection and quantification (LOD-LOQ), linearity, imprecision and the reference ranges in 119 males, 50 women (<45 years) and 120 women (>60 years) for TRACP-5b with the Nittobo assay. We compared both assays in 30 hemodialyzed (HD), and 40 stage 3-5 patients suffering from chronic kidney disease (CKD), 40 patients suffering from rheumatoid arthritis andosteoporosis and 80 post-menopausal women. We measured TRACP-5b, β-crosslaps (β-CTX), bone alkaline phosphatase (B-ALP) and PTH in 20 hemodialyzed (HD) and 40 CKD patients. LOD and LOQ were 0.02 and 0.35 U/L. CV ranged from 8.3 to 4.3% (2/5 samples presenting CV>desirable CV). Method was linear up to of 11.3 U/L. Upper and lower limits of normality were 0.8-7.6 U/L in men, 0.9-4.7 U/L in women <45 and 0.9-7.1 U/L in women >60. The regression equation between the 2 methods was Nittobo=1.13 (95% CI: 1.09-1.16)×iSYS-0.4 (95% CI:-0.5;-0.3). TRACP-5b and b-ALP were in their respective reference ranges for most of CKD and HD patients. That was not the case for β-CTX, which increased with decreasing eGFR. Nittobo TRACP-5b presents interesting analytical features and a good concordance with IDS iSYS. These methods could thus potentially be harmonized.

Persistent Post-COVID-19 Syndrome in Hemodialyzed Patients-A Longitudinal Cohort Study from the North of Poland.

Background: After recovery from COVID-19, patients frequently face so-called “Post-COVID-19 Syndrome” defined by clusters of persistent symptoms lasting for >12 weeks which may arise from any system in the body. The long-term health consequences of COVID-19 in maintenance hemodialyzed (HD) patients remain to be investigated. Methods: In this longitudinal cohort study we described the health consequences in HD patients requiring hospitalization due to COVID-19. They were interviewed three and six months (M3 and M6) after discharge with a series of standardized questionnaires. Results: Of 144 HD patients discharged from the 7th Naval Hospital in Gdansk, 79 participants were enrolled, 39 m (49.4%) and 40 f (50.6%) with a median age of 70.0 (64.0–76.5) and an HD vintage of 40 months (17.5–88). After discharge, 93.7% and 81% reported at least one persistent symptom at M3 and M6, respectively. The most common symptoms were fatigue or muscle weakness (60.76% and 47.04%) and palpitations (40.51% and 30.14%). Dyspnea with an mMRC scale grade of at least 1 was reported by 21.5% before infection, and by 43.03% and 34.25% at M3 and M6, respectively. A decrease in the quality of life was reported in all domains of the EQ-5D-5L questionnaire but mainly in the pain/discomfort and anxiety dimensions. Mean EQ-VAS scores were 69.05, 61.58 and 64.38, respectively. Conclusion: Our study showed that HD patients may still experience persistent symptoms six months after recovery from COVID-19, which can further reduce their already poor health-related quality of life. This study highlights the need for long-term follow-up on these patients for diagnostic and rehabilitation programs.

MO801SAFETY AND EFFICACY OF DENOSUMAB IN HEMODYALISED PATIENTS UP TO 48 MONTHS TREATMENT FOLLOW-UP

Abstract Background and Aims Osteoporosis in hemodialysed (HD) patients with Chronic Kidney Disease - Mineral Bone Disorder (CKD-MBD) is a debilitating clinical condition with complex therapeutic management. In fact, most of the drugs commonly used to counteract osteoporosis are generally contraindicated when Glomerular Filtration Rate (GFR) is lower than 30 ml/min. Denosumab (DMab) is a monoclonal antibody approved for the treatment of osteoporosis and does not require dose adjustment in case of impaired renal function. For this reason, since 2014 this drug has been used by nephrologists for the treatment of osteoporotic patients also in hemodialysis. Although the interest and diffusion in this specialized clinical field are growing, only few data are still available in literature. The aim of the study was to evaluate the efficacy and safety of denosumab in long-term therapies in hemodialysed patients. Method Since November 2013, a total of 19 hemodialysed patients have been treated with denosumab annually (4) or semi-annually (15) for up to 48 consecutive months. During the course of therapy, the laboratory parameters of osteo-mineral metabolism were monitored, and Qualitative UltraSonography (QUS) or Computerized Bone Mineralometry (CBM) were used alternatively, every 30 months and every 2 years, respectively (depending on guidelines recommendation for both radiological methods and timing). Results 7/19 patients completed at least 30 months of follow-up, observing a substantial stability of blood calcium and phosphorus values, against a reduction in the mean values of B-CrossLaps and ostase (respectively from 2975.32 to 1852.25 pg/ml and from 28.13 to 11.93 mcg/L). Comparison of QUS exams demonstrated improved T-score (-4.71 to -4.17) and reduced fracture risk (13% to 8%). The results of the CBMs confirmed the stability of the bone disease at the spine and the improvement of the Tscore at the femoral level (from -3.5 to -3). It should be noted that in our samples two patients achieved the longest observation period (48-month follow-up in continuous therapy), in which the stability of bone damage was observed at CBM compared to the start of treatment. Only one fracture has been recorded. Conclusion We underline that close biochemistry monitoring and careful evaluation of the therapeutic procedures before and after DMab administration helped us to minimise and promptly correct adverse effects due to hypocalcemia. In addition we are particularly satisfied to report in most patients a significant reduction of pain and an improvement of mobility. The results collected are consistent with acceptable safety and demonstrated efficacy of denosumab in hemodialysis patients.

Is Preptin a New Bone Metabolism Parameter in Hemodialysis Patients?

Background: Preptin is a bone-anabolic pancreatic peptide hormone. Its role in bone metabolism has been studied in rats and in patients with diabetes, but its levels and significance in bone metabolism in hemodialyzed (HD) patients is unknown. Methods: The relationships between preptin and anthropometric and biochemical parameters related to bone metabolism were studied in 73 patients on chronic hemodialysis (48 males, 25 females; mean age of 57 years; HD vintage of 69.7 months). Of these subjects, 36 patients had diabetes or impaired glucose tolerance (DM/IGT), and 37 patients had normal glucose tolerance (NGT). Dual-energy X-ray absorptiometry of the femoral neck and lumbar spine were also performed. Results: No differences were observed in preptin levels between DM/IGT and NGT HD patients. Preptin was positively correlated with HD vintage (r = 0.312, p = 0.007). Negative correlations between preptin and bone mineral density (BMD), T-score, and Z-score in the lumbar spine (L2-L4) were observed (r = −0.319, p = 0.009; r = −0.341, p = 0.005; r = −0.375, p = 0.002). Preptin was positively correlated with parathormone (PTH) levels (r = 0.379, p < 0.001) and osteocalcin levels (r = 0.262, p = 0.027). Conclusions: The results indicate that preptin may reflect on bone and mineral metabolism disturbances seen in HD patients. The significant correlation of preptin with PTH and osteocalcin suggests that preptin may be important in indirect measurement of bone turnover in HD patients.

Cytokine and Chemokine mRNA Expressions after Mycobacterium tuberculosis-Specific Antigen Stimulation in Whole Blood from Hemodialysis Patients with Latent Tuberculosis Infection

There have been few reports on the kinetics of hemodialyzed (HD) patients’ immune responses in latent tuberculosis infection (LTBI). Therefore, in the present study, messenger ribonucleic acid (mRNA) expression levels of nine immune markers were analyzed to discriminate between HD patients with LTBI and healthy individuals. Nine cytokines and chemokines were screened through relative mRNA expression levels in whole blood samples after stimulation with Mycobacterium tuberculosis (MTB)-specific antigens from HD patients with LTBI (HD/LTBI), HD patients without LTBI, and healthy individuals, and results were compared with the QuantiFERON-TB Gold In-Tube (QFT-GIT) test. We confirmed that the C-C motif chemokine 11 (CCL11) mRNA expression level of the HD/LTBI group was significantly higher than the other two groups. Especially, the CCL11 mRNA expression level of the >0.7 IU/mL group in the QFT-GIT test was significantly higher than the <0.2 IU/mL group in the QFT-GIT test and the 0.2–0.7 IU/mL group in the QFT-GIT test (p = 0.0043). The present study reveals that the relative mRNA expression of CCL11 was statistically different in LTBI based on the current cut-off value (i.e., ≥0.35 IU/mL) and in the >0.7 IU/mL group. These results suggest that CCL11 mRNA expression might be an alternative biomarker for LTBI diagnosis in HD patients.

Neutrophil-Lymphocyte Ratio (NLR) Reflects Myocardial Inhomogeneities in Hemodialyzed Patients.

Introduction Cardiovascular diseases (CVDs) are a leading cause of death in chronically hemodialyzed (HD) patients. In this group, inflammation exerts significant impact on the prevalence of CVD morbidity and mortality. Spatial QRS-T angle is an independent and strong predictor of CV events, including sudden cardiac death (SCD), both in general population and HD patients. Pathogenesis of widened QRS-T angle is complicated and is not well established. Objectives The study is aimed at evaluating whether inflammation process can contribute to the wide QRS-T angle. Patients and Methods. The retrospective study was performed on 183 HD patients. The control group consisted of 38 patients. Demographic, biochemical, vectorcardiographic, and echocardiographic data were evaluated in all patients. Inflammation process was expressed as neutrophil-lymphocyte ratio (NLR), as well as C-reactive protein (CRP). Results Both NLR (3.40 vs. 1.95 (p < 0.0001)) and spatial QRS-T angle (50.76 vs. 93.56 (p < 0.001)) were higher in the examined group, compared to the control group. Similarly, CRP was higher in the examined group than in the control group (8.35 vs. 4.06 (p < 0.001), respectively). The QRS-T angle correlated with NLR, CRP, some structural echocardiographic parameters, parathormone (PTH), and calcium (Ca) concentrations. Multiple regression analysis showed that NLR is an independent QRS-T angle predictor (r = 0.498, p = 0.0027). The ROC curve analysis indicated the cut-off point of NLR equaled 4.59, where the sensitivity and specificity were the highest for predicting myocardial inhomogeneities expressed as widened QRS-T angle. Conclusion The NLR, as an inflammation marker, may indicate myocardial inhomogeneities in HD patients.

The percentage of non-oxidized PTH concentration remains stable over a period of 1 year in hemodialyzed patients

IntroductionNon-oxidized (n-ox) PTH could better reflect PTH activity. We have evaluated the evolution of n-ox PTH and intact PTH (iPTH) in hemodialyzed (HD) patients over a period of 1 year. Material and methodsWe measured iPTH and n-ox PTH in 66 stable HD patients and we measured iPTH and n-ox PTH at baseline and after 1, 3, 6 and 12 months. We considered that no significant changes in iPTH and n-ox PTH occurred if two consecutives measurements of iPTH and n-ox PTH for the same patient remained in the baseline value ±43%. We also considered that changes over time were concordant if both values of the same patients increased or decreased together (in the same direction) by more than 43%. ResultsThe median [p25; p75] was 229.4 [1.5,4; 352.5] pg/mL for iPTH and 24.4 [15,1; 38.7] pg/mL for n-ox PTH. N-ox PTH fraction represented 11.3 [9.0; 13.7]% of the total iPTH and the ratio n-oxPTH/iPTH ranged from 5.1 to 35.7%. After 1 year, 84% of the patients presented a perfect concordance of the evolution of the 2 moieties and no severe discordance was noticed. ConclusionsThe percentage of n-ox PTH is stable over time in stable HD patients.

Physical activity increases the resistin concentration in hemodialyzed patients without metabolic syndrome.

BackgroundResistin (RES) concentration increases in end-stage renal disease patients. However, there have been no studies defining the role of physical activity in RES concentrations in hemodialyzed (HD) patients. This study was aimed to determine metabolic and inflammatory effects, including RES, of 4-week supervised rehabilitation program in HD patients, with or without metabolic syndrome (MS).MethodsThe study was completed by 28 patients aged 56.9±13.3 years who were HD for 50.6±73.4 months, and 30 controls aged 61.5±8.3 years with normal renal function. Both the groups were divided into two subgroups with respect to MS. Individualized supervised rehabilitation program based on physiotherapy, including exercises, was provided to each subject for 4 weeks. Baseline and post-intervention complete blood count, glycated hemoglobin (HbA1c) and levels of serum RES, leptin, adiponectin, cystatin C, erythropoietin, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6, transforming growth factor- β1, plasminogen activator inhibitor-1 homocysteine, insulin, albumin, parathyroid hormone (PTH), and phosphorus were measured.ResultsCompared to controls, HD patients showed higher baseline leucocytes count and higher serum concentrations of RES, leptin, cystatin C, hs-CRP, TNF-α, homocysteine, phosphorus, PTH while hemoglobin, glucose, and albumin concentrations. A positive correlation between serum albumin and RES concentrations was observed in HD patients. Post-intervention RES increase was observed in HD patients without MS (post-intervention 34.22±8.89 vs baseline 30.16±11.04 ng/mL; P=0.046) while no change was observed in patients with MS and in the control group.ConclusionMS modifies a RES response to the rehabilitation program in HD patients.

Arterial Stiffness in Balkan Endemic Nephropathy, an Environmental Form of Aristolochic Acid Nephropathy.

Balkan endemic nephropathy (BEN), an environmental form of aristolochic acid nephropathy is characterized with later onset and milder forms of hypertension (HT). Thus, we hypothesized that arterial stiffness progresses slower in BEN patients resulting in lower CV mortality. A total of 186 hemodialysed (HD) patients (90 BEN, 96 non-BEN; 67.3 + 13.0 years) were enrolled and followed-up for 25 months. Brachial blood pressure (BP) and pulse wave velocity (PWV) were determined before mid-week dialysis. BEN patients were older (72.1 ± 37.1 vs. 62.8 ± 15.1; p < 0.001), had shorter duration of HT prior commencement of HD than non-BEN patients (36 vs. 84 months; p < 0.001). There were no differences in BP, but BEN patients were treated with less antihypertensive drugs (p < 0.01). BEN patients had lower PWV values at baseline and at the end of follow-up period despite being chronologically older (p < 0.001). Baseline PWV > 10 m/s was associated with higher risk for CV mortality (aHR 1.8 [1.4, 2.4]). In multivariate analyses BEN was predictor of lower PWV. During the follow-up period significantly less CV deaths were observed in BEN vs. on-BEN patients (12 vs. 31; p = 0.001). CV mortality adjusted for other risk factors was significantly lower in BEN group (aHR 0.2 [0.1, 0.5]). Overall BEN patients had longer mean survival time on HD (22.3 vs. 18.2 months; p < 0.001). Observed slower vascular aging (i.e., lower PWV) in BEN patients compared to other ESRD patients is related to the later onset of HT and milder stages of HT during predialytic clinical course and better control of BP and phosphate during HD.

Moving from the second to the third generation Roche PTH assays: what are the consequences for clinical practice?

Background The determination of parathyroid hormone (PTH) is essential for exploring phosphocalcic disorders especially in patients with renal failure. At present, second or third generation PTH assays are available on the market from Roche Diagnostics as well as from others companies but the lack of standardization has complicated the interpretation. Methods We wanted to assess the clinical impact by measuring the PTH levels with the two generations concomitantly on different groups of populations including 46 healthy, 103 pre-dialyzed and 73 hemodialyzed (HD) patients. Results In healthy subjects, the PTH concentrations were not different whatever the generation used, whereas beyond 200 pg/mL, we reported an overestimation of the second generation PTH. In patients with chronic kidney disease (CKD) stage 3-5 the observed differences between the two generations increase with increasing PTH levels and decreasing glomerular filtration rate (GFR). Classification according to the kidney disease: improving global outcomes (KDIGO) revealed a high percentage of discordant results between the two generations (κ coefficient <0.20). These discrepancies are clinically relevant as PTH levels remain the cornerstone for diagnosis and treatment of the CKD-mineral and bone disorder (CKD-MBD). Conclusions The introduction of a new PTH assay generation in clinical practice should be carried out with caution.

Elevated Circulating Osteoprotegerin Levels in the Plasma of Hemodialyzed Patients With Severe Artery Calcification.

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-β, hepatocyte growth factor, fibroblast growth factor 23, osteonectin (ON), osteopontin, osteoprotegerin, and osteocalcin. CCA-IMT and the presence of atherosclerotic plaques was assessed by ultrasound. Fragments of radial artery obtained during creation of HD access were prepared for microscopy and stained for calcifications with alizarin red. RAC was detected in 34 patients (58%). In multiple regression adjusted for dialysis status, TNFRII, ON and Framingham risk score (FRS) were identified as the independent predictors of OPG. Serum OPG above the median value of 7.55 pmol/L significantly predicted the presence of RAC in simple logistic regression (OR 5.33; 95%CI 1.39-20.4; P = 0.012) and in multiple logistic regression adjusted for FRS, dialysis status and CCA-IMT values (OR 6.56; 95%CI 1.06-40.6; P = 0.036). OPG levels above the median were associated with higher CCA-IMT values (1.02 ± 0.10 vs. 0.86 ± 0.13; P < 0.001) and predicted the presence of atherosclerotic plaques in carotid artery (OR 14.4; 95%CI 2.84-72.9; P < 0.001), independently of FRS, dialysis status and RAC. In this study, elevated serum OPG levels correlated with higher CCA-IMT, the presence of atherosclerotic plaques and the severity of the RAC independently of each other. During follow-up, 25 patients (42%) died, including 21 due to CV causes. In multiple Cox regression, OPG above the median predicted overall survival independently of dialysis status, Framingham risk score, CCA-IMT above the median value, and the presence of atherosclerotic plaques in CCA, but not independently of RAC. We postulate that circulating OPG may play a dual role as a marker for both medial arterial calcification and atherosclerosis, hence it seems to be a valuable tool for assessing CV risk in patients with CKD. OPG might be an early indicator of all-cause mortality in CKD patients with advanced medial arterial calcification.

Ultrafiltration rate and diabetes as useful indicators of cardiovascular-related death in hemodialysis patients below 60 years of age

Background: The survival rate of elderly hemodialyzed (HD) patients is commonly thought to be poor. In a prospective, single center, non-interventional, observational study, the cause of all-cause and cardiovascular (CV) and heart failure (HF) mortality in this patient group were examined and compared with a younger cohort (below 60 years). Material/Methods: The study included 223 patients (90 women and 133 men) with age ranging from 34.5 to 75.0 years treated with HD. Median duration of HD was 70.0 months (24.0-120.0). Mortality data was collected over a period of six years. We divided patients into groups: &lt;60 (n=123), ≥60 years (n=100), and with (n=33) and without DM type 2 (n=190). Results: During a six-year follow-up, 100 patients (44.8%) died, including 83 (37.2%) patients who died due to CV reasons. Median follow-up was 2015.0 days (946.0-2463.0) with the median time to death of 1166.0 days (654.5-1631.0). The factors negatively affecting patients’ survival in univariate Cox regression analysis included for all-cause mortality were: inter-dialytic weight gain (IDWG) (hazard ratio [HR]=1.60; p=0.01), ultrafiltration (UF) rate (HR=3.63; p=0.012) for group &lt;60 years; for CV death: UF rate (HR=4.20; p=0.03), DM (HR=5.11; p=0.002) for group &lt;60 years; for HF death: mellitus type 2 (DM) (HR=2.93; p=0.027) for group ≥60 years). In a multivariate Cox regression analysis for patients &lt;60 years, the UF rate was the only independent predictor of all-cause mortality (HR 3.63 (1.34-9.67); p=0.011). Both DM (HR 4.91 (1.71-14.10); p=0.003) and UF rate (HR 3.62 (1.04-12.61); p=0.044) were independent predictors of CV-related mortality in patients &lt;60 years. Conclusions: The UF rate can be a simple, useful indicator of higher long-term all-cause and CV mortality in HD patients &lt;60 years of age. Also, DM may be a predictor of CV–related mortality in younger HD patients.