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BACKGROUND: The predictive value of coagulation markers for venous thromboembolism (VTE) in COVID-19 patients has been investigated with conflicting results. OBJECTIVE: Our aim was to investigate the correlation between biomarkers and VTE and the predictive value of D-dimer for VTE in hospitalized COVID-19 patients. METHODS: Complete blood count, inflammatory and coagulation biomarkers at admission were collected. VTE was defined as diagnosed pulmonary embolism or deep vein thrombosis. Events were defined as in-hospital death or ICU admission. Predictors of VTE were identified with Pearson prediction models. A ROC curve was constructed to assess the predictive value of D-dimer. RESULTS: 1651 participants were included, 111 VTE were identified. Events incidence was higher in the VTE group (49.5% vs 28.2%, p

Introduction: The role of extracorporeal myoglobin removal in the treatment of rhabdomyolysis-associated severe acute kidney injury (AKI) is not yet fully established. High cut-off (HCO) and medium cut-off (MCO) dialysis membrane and cytokine adsorber (CytoSorb®) have been used to this purpose in clinical practice. The data on comparative effectiveness of those methods are scarce. Methods: In this single-center retrospective study, we included patients with AKI and concomitant rhabdomyolysis (myoglobin >20,000 μg/L), who underwent at least one extracorporeal myoglobin removal procedure. The main outcome parameter was myoglobin reduction ratio, whereas albumin was assessed as a safety parameter. Results: We analyzed data for 15 patients, who underwent 28 procedures (13 HCO, 9 MCO, and 6 adsorber). Pre-treatment serum myoglobin levels were similar between the groups and myoglobin reduction was significant in HCO (p = 0.03) and MCO groups (p < 0.01) and borderline significant in adsorber group (p = 0.06). Reduction ratios were comparable between the groups (median 0.64 (inter-quartile range IQR 0.13–0.72), 0.54 (IQR 0.51–0.61) and 0.50 (IQR 0.37–0.62), respectively, p = 0.83). Both pre- and post-procedure serum albumin levels were significantly lower in the MCO group. However, with routine albumin substitution in the HCO group only, serum albumin remained stable during the procedures in all subgroups. Conclusions: Novel MCO membrane might represent the optimal mode of treatment of severe rhabdomyolysis-associated AKI, as it allows for efficient removal of myoglobin, avoids albumin supplementation and is associated with lower costs. For patients requiring cytokine removal, the adsorption capsule can simultaneously reduce cytokine and myoglobin levels.

Background. Systemic inflammatory response syndrome (SIRS) is a complex pathophysiologic response to several hostile stimuli. The excessive release of cytokines during SIRS often leads to a cytokine storm causing refractory hypotension and ultimately multiple organ failure with high mortality. Cytokine removal with hemoadsorption has emerged as a possible adjuvant therapy, but data on IL-6 reduction and clinical outcomes are scarce. We aimed to evaluate the effect of CytoSorb hemoadsorption on laboratory parameters and clinical outcomes in shocked patients with SIRS. Methods. We designed a retrospective analysis of all patients with SIRS treated with CytoSorb in intensive care units. Interleukin 6 (IL-6), hemodynamic parameters (mean arterial pressure – MAP and vasoactive inotropic score - VIS), pH and lactate levels at the beginning, after 6h, 12h, 24h and 48h of CytoSorb treatment were analyzed in the whole cohort and in a subgroup of patients with septic shock. Predicted and observed mortality rates were compared using Chi-squared test. Statistical significance was defined as p Results. After screening 147 patients, we included 118 patients with various etiologies of SIRS (septic shock 69%, SIRS after cardiac arrest 16%, SIRS after acute pancreatitis 6%, other 9%). In all but one patient CytoSorb was coupled with renal replacement therapy. During the observed period of 48 hours, a statistically significant decrease in IL-6 levels, increase in pH, increase in MAP and decrease in VIS was observed already from 6h onward. Reduction of lactate levels became statistically significant at 48 hours. In a subgroup of patients with septic shock, the results were similar, and PCT levels did decreased after 24 hours. Observed ICU and in-hospital mortalities in the whole group were lower than predicted by SOFA (61% vs 79%, p=0.005) and APACHE II (64% vs 78%, p=0.031). There were no serious complications attributed to CytoSorb treatment.Conclusions. Hemoadsorption with CytoSorb used in patients with SIRS of different etiologies was associated with a rapid decrease in IL-6 and hemodynamic improvement, with improved observed vs. predicted survival. These results need to be confirmed in a randomized study.

Background The morphological assessment of urinary erythrocytes (uRBC) is a convenient screening tool for the differentiation of nephrological (dysmorphic) and urological (isomorphic) causes of hematuria. Considering the morphological heterogeneity, this analysis is often perceived as difficult. There is no clear (inter)national consensus and there is a lack of external quality assessment programs. To gain insight into the heterogeneity within and between laboratories, we scrutinized the current state of this analysis in Dutch medical laboratories. Methods The laboratories, affiliated with the Dutch Foundation for Quality Assessment in Medical Laboratories, were invited to participate in a web-based survey, consisting of two questionnaires. The first one provided information about the institution and laboratory organization, and the second explored the variability in the morphological analysis of uRBC on the basis of categorization of 160 uRBC images. Statistical analysis was premised on binomial significance testing and principal component analysis. Results Nearly one third of the Dutch medical laboratories (65/191) with 167 staff members participated in the survey. Most of these laboratories (83%) were an integral part of secondary care. The statistical analysis of the evaluations of the participants in comparison to the consensus (three experts from two different medical laboratories) suggested a great degree of heterogeneity in the agreement. Nearly half of the participants consciously disagreed with the consensus, whereas one fifth demonstrated a random relationship with it. Conclusions In Dutch medical laboratories, results from morphological analysis of uRBC are heterogeneous, which point out the necessity for standardization and harmonization.

Background and aim Glomerular erythrocyturia (GlomEry) is usually associated with proliferative kidney diseases. In our retrospective cohort, we aimed to validate the predictive value of GlomEry criteria ≥ 40% dysmorphic erythrocytes (DysEry) or ≥ 5% acanthocytes (AcaEry) or at least 1 erythrocytic cast (CastEry) and of two new indices - the count of DysEry per high power field (HPF) and per microliter of urine (Stansfeld-Webb (SW)) method, for proliferative disease. Materials and methods We included patients with erythrocyturia from 2015 to 2016. Based on renal histology, we divided them into a proliferative and a non-proliferative disease group. Urine erythrocyte count was done using SW and urinary sediment examination was carried out by skilled nephrologists. Sensitivity, specificity, and cutoff values were determined using ROC curves. Results We included 90 patients (33% women), median age of 63 (IQR 51, 71) years. In the proliferative group, proteinuria was lower (2.4 vs. 6.6 g/day), and SW erythrocyturia was higher (174 (IQR 60, 353) vs. 44 (IQR 20, 67) × 106/L) than in the non-proliferative group. The threshold to differentiate between the proliferative and non-proliferative group was determined at ˃ 43% of DysEry (sensitivity 73%, specificity 79%, AUC 0.808) and at ˃ 2% AcaEry (sensitivity 71%, specificity 56%, AUC 0.647). No significant difference in CastEry was found between groups. Among tested parameters, the calculated number of DysEry/HPF > 6.7 (sensitivity 77%, specificity 92%, AUC 0.878), followed by DysEry/SW > 28 × 106/L (sensitivity 76%, specificity 86%, AUC 0.879), discriminated those two groups best. Conclusion In concordance with known GlomEry criteria, > 43% of DysEry predicted proliferative kidney disease, whereas CastEry did not, and AcaEry predicted poorly. The best predictor of proliferative glomerular disease was DysEry/HPF, closely followed by DysEry/SW.

Background and Aims Severe rhabdomyolysis often causes acute kidney injury (AKI). If severe, AKI significantly reduces myoglobin removal through the kidneys. Given molecular size of myoglobin, extracorporeal removal using newer hemodialysis membranes and adsorption techniques is possible, although its role on clinically significant outcomes is not yet fully established. We aimed to compare the efficacy of high cut-off (HCO) membrane, medium cut-off (MCO) membrane and Cytosorb® adsorber on myoglobin removal. Method In this retrospective study we included 15 patients with AKI and concomitant rhabdomyolysis with severely increased myoglobin (>20.000 µg/L), who underwent at least one extracorporeal procedure with the intention of extracorporeal myoglobin removal. There were 28 procedures performed: 13 HCO (Theralite®, Gambro) dialysis, 9 MCO (Theranova®, Gambro) dialysis and 6 adsorber (Cytosorb®, Cytosorbents) procedures. Serum myoglobin and albumin levels were recorded from the time frame of up to 12 hours prior to and up to 12 hours after the index procedure and reduction rates (RR) for myoglobin were calculated. Albumin levels were compared before and after procedure as a safety parameter. Results Treatment duration differed significantly and was the longest for Cytosorb® adsorber (median 11 h) and the shortest for MCO membrane (median 5 h). Pre-treatment serum myoglobin levels were comparable across the groups. Reduction in myoglobin during procedure was significant for HCO and MCO and borderline significant in adsorber group, with respective median RR of 0.64, 0.54 and 0.50 (p = 0.83). Routine albumin substitution was implemented only in HCO group, but serum albumin levels were stable in all subgroups. Conclusion In this preliminary observational study we found comparable effectiveness of a novel MCO and ‘standard’ HCO dialysis membrane for serum myoglobin removal in patients with severe AKI. Cytokine adsorber showed borderline effectiveness, but the number of procedures in this group was small. MCO dialysis is associated with lower costs and no need for albumin supplementation and therefore might be the optimal mode of treatment of severe rhabdomyolysis-associated AKI. For patients with multiorgan failure requiring cytokine removal and severe myoglobinemia, hemoadsorption can reduce cytokine and myoglobin levels simultaneously.

Background Treatment of idiopathic membranous nephropathy with rituximab was introduced more than a decade ago following experimental data that suggested involvement of B-cell-mediated reactions in its pathogenesis. It was a logical step towards a more selective therapy with less severe side effects as compared to the recommended first-line immunosuppressive therapy with corticosteroids and different immunosuppressant drugs. Methods We retrospectively analyzed the anonymous data of patients who were treated with rituximab for idiopathic membranous nephropathy at our institution from January 2006 to July 2016. Daily proteinuria and serum creatinine were analyzed 3, 6, 9, and 12 months after rituximab application. The patients were divided into 4 groups according to proteinuria. We separately analyzed remission rates in the whole group and in groups with different quantity of daily proteinuria. Other history data and laboratory parameters were also compared within different groups of patients. Results The study involved 29 rituximab treatments in 26 patients: 7 (26.9%) female and 19 (73.1%) male patients. In 16 out of 29 treatment cases (55.1%), patients had been previously treated with cyclophosphamide and steroids, or cyclosporine with low dose of steroids, or both. In 72.4% of patients, antiphospholipase A2 receptor antibodies were present. In 2 cases of treatment (6.9%), patients received rituximab 375 mg/m2 of body surface area in 3 and 4 weekly doses, respectively. In all other cases, repeated rituximab applications were given as needed according to the levels of circulating CD-20 B-cells. The total remission rate in our cohort of patients was 37.9% (11 out of 29 cases). The average serum creatinine in the group of patients who achieved remission was significantly lower than in the group without remission (86.5 vs. 155.5 µmol/L, p = 0.003). There was no difference in the duration of the disease prior to treatment with rituximab between the groups (53.6 and 56.4 months, respectively). The remission rate was highest in the group with daily proteinuria less than 4 g per day (83.3%). There were no remissions in the group of patients with daily proteinuria more than 12 g per day. Conclusion The remission rate after rituximab treatment in our cohort of patients with idiopathic membranous nephropathy was lower than in other studies. The reason for this is possibly the application of a single dose of rituximab in the majority of patients, which might have been insufficient in patients with higher proteinuria. .

Association of higher serum levels of uremic toxins and inflammatory markers with poorer physical performance is understudied. We measured the six-minute walk test (6MWT), 10 repetition sit-to-stand test (STS-10), handgrip strength (HGS), and Human Activity Profile (HAP) questionnaire score in 90 prevalent hemodialysis patents, with low comorbidity to reduce the potential confounding of concomitant disease. Midweek pre-dialysis serum levels of asymmetric dimethyl-arginine (ADMA), &beta, 2-microglobulin (B2M), high-sensitivity C-reactive protein (hs-CRP), indoxyl sulfate (IS), insulin-like growth factor 1 (IGF-1), interleukin 6 (IL-6), myostatin, and urea were analyzed as predictor parameters of physical performance measures in adjusted models. Serum levels of most measured toxins were not significantly related to performance, except for ADMA, which was significantly related to poorer performance in the STS-10 test (B = 0.11 &plusmn, 0.03 s, p &lt, 0.01). Higher hs-CRP was associated with poorer results in the 6MWT (B = &minus, 2.6 &plusmn, 0.97 m, p &lt, 0.01) and a lower HAP score (B = &minus, 0.36 &plusmn, 0.14, p = 0.01). There were no other significant associations found. We conclude that inflammation may be a more important pathway to physical impediment than uremic toxemia. This suggests that there is a large physical rehabilitation potential in non-inflamed uremic patients.

BACKGROUND Complex and longstanding bone disease superimposed by harmful influences of immunosuppression is the reason for increased risk of bone fracture in kidney transplant recipients. The aim of our study was to analyze the incidence and prevalence of nonvertebral bone fractures and early (in the first post-transplant year) clinical and laboratory risk factors for suffering bone fracture in the long-term post-transplant period. METHODS Clinical and laboratory data as well as bone mineral density (BMD) measurements of 507 first kidney transplant recipients who were transplanted in the period from 1976 to 2011 were analyzed. RESULTS The mean age of included patients was 54.3 ± 12.0 years, there were 45% females, and mean time on renal replacement treatment prior to transplantation was 63.4 ± 43.6 months. The average observation time post-transplant was 9.7 years (1.4 - 36.3 years). Post-transplant, 64 (12.6%) patients suffered 89 nonvertebral fractures (44 patients suffered 1 fracture, 15 patients 2 fractures, and 5 patients 3 fractures). Patients with fractures had significantly lower late BMD of femoral neck in the period of 1 - 10 years post-transplant, had osteopenia and osteoporosis more frequently in the same time period, and higher serum alkaline phosphatase in the first year post-transplant. 13 patients (13/64, 20.3%) had major fractures. Patients with major fractures were significantly older than patients with no major fractures and had lower serum albumin. Frequency of treatment with bisphosphonate, calcium, or phosphate did not differ between the groups. Vitamin D supplement (active form in 98% of cases) was prescribed more frequently in the group without fractures, but this was not statistically significant. CONCLUSION Fracture rate in our transplant patient population was comparable to that reported in the literature. Except for a higher level of serum total alkaline phosphatase in the fracture group, we found no other early laboratory risk factors for bone fractures. BMD at the femoral region 1 - 10 years after kidney transplantation but not BMD at the time of transplantation was a risk factor for nonvertebral fractures. Osteopenia and osteoporosis in the post-transplant period were found to be a fracture risk factor. .

BACKGROUND We present a case of acute rhabdomyolysis in the setting of interferon-β treatment and concomitant pomelo juice ingestion, with concern of possible pharmacological interaction, which has not yet been described in the literature. CASE PRESENTATION A young Caucasian female with multiple sclerosis on chronic therapy with interferon-β presented with acute rhabdomyolysis after mild exercise and concomitant ingestion of pomelo extract. After stopping the suspected drugs, the signs of rhabdomyolysis diminished, the subsequent course was favorable. CONCLUSIONS The most probable cause of rhabdomyolysis in our patient could have been the combination of interferon effect, which down-regulates P450 expression, with inhibition of the P450 activity by furanocoumarin derivatives from pomelo juice. Therefore, patients treated with drugs that have a possible interaction with inhibitors of cytochrome P450 should be warned against pomelo ingestion. .