High Plasma Angiopoietin-2 Levels Predict the Need to Initiate Dialysis within Two Years in Patients with Chronic Kidney Disease.

Volume status, congestion, endothelial activation, and injury all play roles in glomerular filtration rate (GFR) decline. In this study, we aimed to determine whether the plasma endothelial and overhydration markers could serve as independent predictors for dialysis initiation in patients with chronic kidney disease (CKD) 3b-5 (GFR < 45 mL/min/1.72 m2) and preserved ejection fraction. A prospective, observational study in a single academic center was conducted from March 2019 to March 2022. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were all measured. Lung ultrasound (US) B-lines, bioimpedance, and echocardiography with global longitudinal strain (GLS) were recorded. The study outcome was the initiation of chronic dialysis (renal replacement therapy) during 24 months of follow-up. A total of 105 consecutive patients with a mean eGFR of 21.3 mL/min/1.73 m were recruited and finally analyzed. A positive correlation between Ang-2 and VCAM-1 and BTP was observed. Ang-2 correlated positively with BNP, cTnI, sCr, E/e', and the extracellular water (ECW)/intracellular water (ICW) ratio (ECW/ICW). After 24 months, a deterioration in renal function was observed in 47 patients (58%). In multivariate regression analysis, both VCAM-1 and Ang-2 showed independent influences on risk of renal replacement therapy initiation. In a Kaplan-Meier analysis, 72% of patients with Ang-2 concentrations below the median (3.15 ng/mL) survived without dialysis for two years. Such an impact was not observed for GFR, VCAM, CCP, VEGF-C, or BTP. Endothelial activation, quantified by plasma levels of Ang-2, may play a key role in GFR decline and the need for dialysis initiation in patients with CKD 3b, 4, and 5.

Chemokines and Cytokines Profiles in Patients with Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis: A Preliminary Study.

The damage to small vessels in AAV and inflammatory reactions are accompanied by the release of various chemokines and cytokines. Using a flow cytometry technique, we assessed the levels of specific cytokines, namely IL-1ß IL-6, IL-8, IL-10, IL12p70, and TNF, and chemokines, IFN-α, IP-10, and MIG in the serum from 9 healthy volunteers and 20 AAV patients, where 11 of the patients were not treated and evaluated at the time of diagnosis and 9 were already diagnosed and taking CY + GCS. The obtained results were then compared considering the activity of the disease, the type and titre of the ANCA antibodies, the inflammatory status, and the kidneys' condition. Amongst others, the IL-6, IL-8, IL-10, TNF, and MIG levels were much higher in the serum of AAV patients than in healthy controls, whereas the level of IL-1ß was higher in healthy volunteers. Additionally, the levels of IL-6, IL-10, IP-10, and MIG negatively correlated with the eGFR level, while the level of IFN-α positively correlated with the titre of PR3-ANCA. As most of the molecules are implicated in trafficking primed neutrophils towards small vessels, looking for links between the levels of these cytokines/chemokines and the clinical symptoms of AAV may facilitate the diagnosis and predict the progression of the disease.

Artificial neural network - an effective tool for predicting the lupus nephritis outcome.

BACKGROUND: Lupus nephropathy (LN) occurs in approximately 50% of patients with systemic lupus erythematosus (SLE), and 20% of them will eventually progress into end-stage renal disease (ESRD). A clinical tool predicting remission of proteinuria might be of utmost importance. In our work, we focused on predicting the chance of complete remission achievement in LN patients, using artificial intelligence models, especially an artificial neural network, called the multi-layer perceptron. METHODS: It was a single centre retrospective study, including 58 individuals, with diagnosed systemic lupus erythematous and biopsy proven lupus nephritis. Patients were assigned into the study cohort, between 1st January 2010 and 31st December 2020, and eventually randomly allocated either to the training set (N = 46) or testing set (N = 12). The end point was remission achievement. We have selected an array of variables, subsequently reduced to the optimal minimum set, providing the best performance. RESULTS: We have obtained satisfactory results creating predictive models allowing to assess, with accuracy of 91.67%, a chance of achieving a complete remission, with a high discriminant ability (AUROC 0.9375). CONCLUSION: Our solution allows an accurate assessment of complete remission achievement and monitoring of patients from the group with a lower probability of complete remission. The obtained models are scalable and can be improved by introducing new patient records.

Subphenotypes of ANCA-associated vasculitis identified by latent class analysis.

OBJECTIVES: ANCA-associated vasculitides (AAV) are a heterogeneous group of rare diseases with unknown aetiology and the clinical spectrum ranging from life-threatening systemic disease, through single organ involvement to minor isolated skin changes. Thus, there is an unmet need for phenotype identification, especially among patients with granulomatosis with polyangiitis (GPA). Patients with microscopic polyangiitis (MPA) seem to be clinically much more uniform. Recently, three subcategories of AAV have been proposed and described as non-severe AAV, severe PR3-AAV, and severe MPO-AAV. METHODS: In line with these attempts, we decided to use an unbiased approach offered by latent class analysis (LCA) to subcategorise GPA and MPA in a large cohort of Polish AAV patients included in a multicentre POLVAS registry. RESULTS: LCA of our AAV group identified a four-class model of AAV, including previously proposed three subphenotypes and revealing a fourth (previously not described) clinically relevant subphenotype. This new subphenotype includes only GPA patients, usually diagnosed at a younger age as compared to other groups, and characterised by multiorgan involvement, high relapse rate, relatively high risk of death, but no end-stage kidney disease. CONCLUSIONS: Based on multiple clinical and serological variables, LCA methodology identified 4-class model of AAV. This newly described fourth class of AAV may be of clinical relevance and may require prompt diagnosis and aggressive treatment due to the multiorgan involvement, high risk of relapse and marked mortality among these relatively young GPA subjects.

Carotid artery tortuosity may pose a problem during insertion of the tunneled catheter for hemodialysis.

Tortuosity of the carotid artery is usually an asymptomatic vascular abnormality and is discovered accidentally during cerebral angiography. These vascular changes may aggravate surgical procedures in the neck region. We described a technique of permanent catheter insertion in patients with renal graft failure in whom renal replacement therapy was necessary. Severe tortuosity of cervical arteries may make this procedure more difficult, necessitating a special technique, that is, full image monitoring.

Dialysis Catheter Insertion with Extended Ultrasound Monitoring.

INTRODUCTION: Dialysis catheter insertion is a routine procedure performed when there is necessity of urgent renal replacement therapy initiation. Due to limited access, higher costs, and long waiting times for fluoroscopy, alternative visualization methods are introduced into clinical practice. One of the most promising is transthoracic echocardiographic monitoring of guide-wire introduction. OBJECTIVE: The feasibility of the technique was verified by nephrologists inserting dialysis catheters. METHODS: A single center prospective trial was performed (NCT03727581). Introduction of guide-wire was monitored with ultrasound to confirm correct position of the wire in the inferior vena cava (IVC) or right atrium (RA). The study group included 30 patients, 19 males and 11 females, 25-83 years old. RESULTS: It was possible to obtain a good picture of IVC in the majority of patients. In 20 (66.7%) cases, IVC view was excellent; in 9 (30%) cases, was fair; and in 1 (3.3%) patient, we failed to visualize IVC. The guide-wire was identified in IVC in 12 (42.8%) patients, in another 9 (32.1%) patients guide-wire was visible in IVC after withdrawing and advancing it, and in RA in 6 (21.4%) patients. Catheters were successfully placed in 29 (96.7%) patients. CONCLUSIONS: Detection of the guide-wire confirms correct course of the procedure and increases the safety of catheter insertion without fluoroscopy.

Dialysis membranes: A 2018 update.

Dialysis membranes are the basic element of a hemodialyzer. Synthetic and natural materials characterized by various fiber arrangements are used in their production. The most up-to-date ones are made of synthetic polymers such as polyamide, phosphatidylserine (PS), polyacrylonitrile-based fiber (PAN), polyarylethersulfone, polyethersulfone, or polymethylmethacrylate. Dialysis membranes are characterized by the ability to remove uremic molecules, which can be divided into small water-soluble compounds, protein-bound compounds and larger "middle molecules". Newer membranes such as medium cut off membranes (MCO) allow the removal of a wider spectrum of uremic molecules, which reduces the risk of late complications of dialysis. Dialysis membranes are used in therapy methods such as low flux, high flux or HDx therapy. An important aim in dialysis membrane development is to increase their biocompatibility. Insufficient biocompatibility can result in complement activation or platelet activation, which can lead to an increased risk of cardiovascular complications. The aim of the study is to discuss the latest reports on dialysis membranes.

Dialysis-Related Parameters Influence Remodeling in the Venous Part of the Native Arteriovenous Fistula.

BACKGROUND: The aim of this study was to evaluate the association of hemodynamic parameters related to hemodialysis and antropometric parameters of patients with changes in the venous part of the arteriovenous fistula (AVF) at points of needling. METHODS: Two hundred forty-two hemodialysis (HD) patients (60.3% men), with median age 65 (interquartile range [IQR] 56-75) years, on HD treatment for a median of 49 (IQR 20-88) months with functioning fistula were recruited for the study. The history of vascular access, comorbidity, antropometric (body mass index, body surface area, and body composition), and dialysis-related parameters were analyzed. The cross-sectional area of upper extremity vessels were measured using ultrasound and included 2 points: A (arterial point for blood aspiration) and V (venous point for returning the blood after purification). The difference between A and V (A-V) was calculated. RESULTS: The median cross-sectional area of A was larger than V (1.04 [IQR 0.58-1.7] vs. 0.74 cm2 [IQR: 0.41-1.39], P <0.0001). The median difference between A and V (A-V) was 0.17 cm2 and positively correlated with mean blood flow (Qb), effective Kt/V, and time of AVF use. Other analyzed factors had no influence on A-V. In the multivariate analysis, the independent factor increasing the difference (A-V) was mean blood flow measured during HD sessions. CONCLUSIONS: The needling and utilization of AVF for hemodialysis may affect vein anatomy, namely causing dilatation at the arterial point and narrowing at venous point of AVF. We suggest that blood pump velocity of the dialysis machine may have an impact on these changes, but practical importance of these findings has to be elucidated. The significance of (A-V) factor in the prognosis of fistula complications should be further studied and confirmed in the prospective trials.

The snuffbox fistula should be preferred over the wrist arteriovenous fistula.

OBJECTIVE: The snuffbox arteriovenous fistula (SBAVF) is the most distal native vascular access. Although published data show a favorable outcome, the SBAVF is not strongly recommended by the guidelines. The present study compared the patency of SBAVFs and wrist AVFs (WAVFs). METHODS: All 416 AVFs created by the same nephrologist from March 2006 to October 2014 were reviewed. From 416 procedures, 47 SBAVFs and 77 WAVFs with vessels suitable for a SBAVF were selected. RESULTS: Although vessel diameters used for construction of the SBAVFs were smaller than those used for WAVFs, the outcome of vascular access was similar. At 18 months, primary patency was 72% for SBAVF and 65% for WAVF (P = .48), and secondary patency was 93% for SBAVF and 94% for WAVF (P = .89). CONCLUSIONS: In our experience, a SBAVF performs as well as a WAVF up to 18 months after creation. We suggest favoring SBAVF, especially in young patients without comorbidities, as the primary vascular access.

The Level of Anxiety and Depression in Dialysis Patients Undertaking Regular Physical Exercise Training--a Preliminary Study.

BACKGROUND/AIMS: The aim of the study was to evaluate the effects of a six-month physical training undertaken by haemodialysis (HD) patients, on the depression and anxiety. METHODS: Patients with end stage renal disease (ESRD) were recruited from the dialysis station at the Department of Nephrology and Transplantation Medicine in Wroclaw. Physical training took place at the beginning of the first 4-hours of dialysis, three times a week for six months. A personal questionnaire, Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) were used in the study. RESULTS: A total of 28 patients completed the study: 20 were randomised to endurance training and 8 were randomised to resistance training. Statistical analysis of depression and anxiety at the initial (t1) and final examination (t2) indicated a significant reduction in depression and anxiety, particularly anxiety as a trait (X2) in the whole study group. The change in anxiety as a state correlated with the disease duration, duration of dialysis and the initial level of anxiety as a state (t1X1). The change in anxiety as a trait significantly correlated with age and the initial level of anxiety (t1X2). CONCLUSIONS: Undertaking physical training during dialysis by patients with ESRD is beneficial in reducing their levels of anxiety and depression. Both resistance and endurance training improves mood, but only endurance training additionally results in anxiety reduction.

Balloon Dilatation for Removal of an Irretrievable Permanent Hemodialysis Catheter: The Safest Approach.

Long-term hemodialysis catheter dwell time in the central vein predisposes to fibrin sheath development, which subsequently causes catheter malfunction or occlusion. In very rare cases, the catheter can be overgrown with fibrin and rigidly connected with the vein or heart structures. This makes its removal almost impossible and dangerous because of the possibility of serious complications, namely vein and heart wall perforation, bleeding, or catheter abruption in deep tissues. We describe two cases in which standard retrieval of long-term catheters was not possible. Balloon dilatation of catheter lumens was successfully used to increase the catheter diameter with simultaneous tearing of the fibrin sheath surrounding it. This allowed the catheter to be set free safely. Based on this experience, we present recent literature and our point of view.

External dilator-assisted banding for high-flow hemodialysis arteriovenous fistula.

Creation of arteriovenous fistula (AVF) may lead to left ventricle hypertrophy and predispose for development or worsening of heart failure. It was postulated to reduce access blood flow if exceeded 2 L/min or cardiac index was higher than 3.0 L/min/m(2). Numbers of techniques decreasing flow were described. The major disadvantage was the complexity of procedure and necessity of intraoperative flow measurement needed to establish desired flow. The technique of dilator-assisted banding with no endovascular catheterization is presented. After blunt dissection non absorbable thread was placed around vessel and tied over the dilator. Then the dilator was gently removed and blood flow was confirmed by palpation. We performed 12 banding procedures. Mean brachial blood flows were 3733.2 ± 826.2 mL/min preoperatively and 1461.2 ± 337.7 mL/min after surgery. Mean flow reduction was 2272.2 ± 726.9 mL/min. The external dilator-assisted banding is a feasible method for vascular access flow reduction without necessity of endovascular catheterization.

Treatment of renal ANCA-associated vasculitides.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of small vessel vasculitides which commonly affect the kidneys, manifesting as rapidly progressive glomerulonephritis. In this review, we present different treatment methods (e.g. cyclophosphamide, rituximab, plasma exchange) used for remission induction and maintenance in renal AAV. We also discuss treatment options in relapsing and refractory disease and for patients with end-stage renal disease due to AAV. In addition, we enumerate the various risk factors associated with relapsing and refractory disease, quality of life impairment and decreased renal and patient survival in AAV. Finally we present information on new, potentially applicable agents which can further help modify the disease course, thereby leading to increased patient survival.

Use of Plastic Needles for Early Arteriovenous Fistula Cannulation.

BACKGROUND: The native arteriovenous fistula (AVF) needs maturation before it can be used. Needling done before time may result in haematoma formation, miscannulation or even access loss. METHODS: This retrospective study included 20 patients with AVFs punctured with fluoroplastic dialysis catheters within 30 days after access creation and 19 historical controls. RESULTS: The time to first puncture was 2-29 days for the study group and 1-26 days for the control group. The incidences of haematoma were 16.7 and 48 per 1,000 dialysis sessions for plastic and metal needles, respectively. Estimated primary functional fistula survival at 3, 6 and 12 months were 95, 90 and 74% for the study group and 79, 67 and 60% for the control group (p = 0.106), respectively. CONCLUSIONS: Use of plastic needles enables safe AVF cannulation. If applied judiciously, it can minimize or even avoid catheter use.

Different body fluid volumes measured by single- and multi-frequency bioelectrical impedance analyzers in overweight/obese renal patients.

INTRODUCTION: Bioelectrical impedance analysis (BIA) is an affordable, non-invasive and fast alternative method to assess body composition. The purpose of this study was to compare two different tetrapolar BIA devices for estimating body fluid volumes and body cell mass (BCM) in a clinical setting among patients with kidney failure. METHODS: All double measurements were performed by multi-frequency (MF) and single-frequency (SF) BIA analyzers: a Body Composition Monitor (Fresenius Medical Care, Germany) and BIA-101 (Akern, Italy), respectively. All procedures were conducted according to the manufacturers' instructions (dedicated electrodes, measurement sites, positions, etc). Total body water (TBW), extracellular water (ECW), intracellular water (ICW) and BCM were compared. The study included 39 chronic kidney disease patients (stage III-V) with a mean age of 45.8 ± 8 years (21 men and 18 women) who had a wide range of BMI [17-34 kg/m2 (mean 26.6 ±5)]. RESULTS: A comparison of results from patients with BMI <25 vs ≥25 revealed a significant discrepancy in measurements between the two BIA devices. Namely, in the group with BMI <25 (n=16) acceptable correlations were obtained in TBW (r 0.99; p<0.01), ICW (0.92; p<0.01), BCM (0.68; p<0.01), and ECW (0.96 p<0.05), but those with BMI ≥25 (n=23) showed a discrepancy (lower correlations) in TBW (r 0.82; p<0.05), ICW (0.78; p<0.05), BCM (0.52; p<0.05), and ECW (0.76; p<0.01). CONCLUSIONS: Since estimates of TBW, ICW and BCM by the present BIA devices do not differ in patients with BMI <25, they might be interchangeable. This does not hold true for overweight/obese renal patients.

[Vascular access in diabetic patients. Are these patients "difficult"?]. / Dostep naczyniowy u chorych na cukrzyce. Czy sa to chorzy problematyczni?

Diabetics with stage V chronic kidney disease (CKD) on hemodialysis (HD) are considered as "difficult patients", because of problems with creation of the vascular access. There is controversy regarding the results and recommendations for preparation of the vascular access in these patients. The aim of this retrospective study was to evaluate the results of creating different types of arteriovenous fistula (AVFs) in consecutive series of patients starting dialysis treatment. The analysis was performed in 741 patients (385 females and 356 males), average age 61.4±7 years, who started dialysis treatment in our department between January 2005 and December 2012. Native AVFs were created in all patients. No patients received an AVF requiring synthetic graft material. The number of patients with diabetic nephropathy was 166 (22.4%). Among them, 30 (18%) had type 1 diabetes and 136 (82%) type 2. In this group the occurrence of calcification in the forearm artery was estimated on the basis of physical examination, Allan's test, Doppler ultrasound and forearm X-ray. In a subgroup of patients with atherosclerotic changes in the arterial system the frequency of failed AVFs was analyzed. These results were compared with the group without diabetes. The number of procedures necessary for successfu AVF creation and type of access was counted in both groups. The assessment of the procedure frequency and AVF location in diabetic and in non-diabetic patients was made by χ² test with Yates correction. In the group of 166 patients with diabetes, in 100 cases (60%) atherosclerotic changes in forearm arteries were observed. In a subgroup of 30 patients with type 1 diabetes atherosclerosis was observed in 17 adults (57%). In this subgroup creation of a suitable forearm AVF in the first procedure in 9 patients was possible and in the other 8 cases the atherosclerotic changes necessitated repeated procedures and were an important obstacle to create the AVF. In the subgroup of 136 patients with type 2 diabetes, atherosclerosis in the forearm artery was observed in 83 cases (61%). In this subgroup the creation of a native AVF was possible in 40 patients during the first procedure and in 43 cases additional intervention was needed, but only in 8 cases was atherosclerosis the cause of fistula failure. Generally, among 166 patients only in 16 cases (10%) did atherosclerosis present an important obstacle for AVF creation, but the number of necessary procedures to create one functioning AVF was significantly greater in this population (2 v 2.7, p=0.0001). A functioning AVF in patients with diabetes was found significantly frequently in the arm localization in comparison to non-diabetic patients (4.3 v 2%, p=0.0478). Atherosclerotic changes in forearm arteries in diabetic patients appear in 60% of hemodialysis patients and make it difficult to create an AVF only in 10% of diabetic patients, but it is possible to create a native AVF in 90% of diabetic patients, although this requires more procedures. In patients with diabetes, AVF in the wrist region should be preferred.

[Intentional and Non-Intentional Distortion of Research Findings]. / Swiadome i nieswiadome znieksztalcanie wyników badan naukowych.

The flood of scientific information increases the risk of research findings distortion. The authors brought attention to the possible pitfalls of statistical inference in biomedical research. Due to intentional or non-intentional errors in study design and size, data collection and inappropriate statistical analysis some of research findings are false or exaggerated. Researchers excessively motivated to publish all possible study results sometimes seek any possible way to achieve p-value less than 0.05. False-positive study results can be obtained in underpowered studies, excessive flexibility in study designs and participants recruitment, probing different control groups, creating special subgroups or changing statistical tests.

Consider use of a collateral venous circuit before abandoning the arteriovenous fistula--the experience of a complex vascular access case.

We describe a 65-year-old woman with diabetes on hemodialysis maintenance, with a number of complications associated with high-flow arteriovenous fistula (AVF, anastomosis between brachial artery and medial vein of the forearm) requiring an extended diagnostic and individual approach. The patient was admitted to our hospital because of pain, edema of the limb, hand ischemia, and infection caused by steal syndrome. To reduce fistula flow, banding of the proximal cephalic vein was performed. Simultaneously because of necrosis, amputation of the fifth finger was necessary. Following this procedure, the cephalic vein on the arm thrombosed. The fistula was patent through the collateral circuit, which was diagnosed in detail during the late course. A long course of antibiotics and sessions in a hyperbaric chamber allowed limb rescue. Single-needle dialysis was carried out because of problems in finding an appropriate second place. After an episode of bleeding from the puncture site caused by ulceration, we were forced to search for an alternative needling point. On the basis of ultrasound scans, an anatomic schema of the blood circuit was created. The fistula demonstrated flow from the brachial artery resulting in retrograde flow in the section of the cephalic vein distal to the anastomosis in the upper forearm. This was then seen to drain in an antegrade direction via the median vein of the forearm after the 2 vessels connected in the mid forearm. Using the diagram, 2 alternative places for needling were found and it allowed the adequate hemodialysis to be continued. Complex and complicated cases associated with native AVF could be resolved using simple diagnostic tools to preserve the fistula use for hemodialysis. Both clinical examination and ultrasound scan with the Doppler option appear to be valuable methods for finding the optimal cannulation place.

Changes of Dissociative Properties of Hemoglobin in Patients with Chronic Kidney Disease.

Background: The ability of hemoglobin to bind and dissociate oxygen is crucial in delivering oxygen to tissues and is influenced by a range of physiological states, compensatory mechanisms, and pathological conditions. This may be illustrated by the oxyhemoglobin dissociation curve (ODC). The key parameter for evaluating the oxygen affinity to hemoglobin is p50. The aim of this study was to evaluate the impact of hemodialysis on p50 in a group of patients with chronic kidney disease (CKD). An additional goal was to assess the correlation between p50 and the parameters of erythropoiesis, point-of-care testing (POCT), and other laboratory parameters. Methods: One hundred and eighty patients (106 male, 74 female), mean age 62.5 ± 17 years, with CKD stage G4 and G5 were enrolled in this cross-sectional study. Patients were divided into two groups, including 65 hemodialysis (HD) patients and 115 patients not receiving dialysis (non-HD). During the standard procedure of arteriovenous fistula creation, blood samples from the artery (A) and the vein (V) were taken for POCT. The causes of CKD, as well as demographic and comorbidity data, were obtained from medical records and direct interviews. Results: The weekly dose of erythropoietin was higher in HD patients than in non-HD patients (4914 ± 2253 UI vs. 403 ± 798 UI, p < 0.01), but hemoglobin levels did not differ between these groups. In the group of non-HD patients, more advanced metabolic acidosis (MA) was found, compared to the group with HD. In arterial and venosus blood samples, the non-HD group had significantly lower pH, pCO2 and HCO3-. This group had a higher proportion of individuals with MA with HCO3- < 22 mmol/L (42% vs. 24%, p < 0.01). The absolute difference of p50 in arterial and venous blood was determined using the formula Δp50 = (p50-A) - (p50-V). Δp50 was significantly higher in the HD group in comparison to non-HD (0.08 ± 2.05 mmHg vs. -0.66 ± 1.93 mmHg, p = 0,02). There was a negative correlation between pH and the p50 value in arterial (pH-A vs. p50-A, r = -0.56, p < 0.01) and venous blood (pH-V vs. p50-V, r = -0.45, p < 0.01). In non-HD patients, hemoglobin levels correlated negatively with p50 (r = -0.29, p < 0.01), whereas no significant relation was found in HD patients. Conclusions: The ODC in pre-dialysis CKD (non-HD) patients is shifted to the right due to MA, and this is an additional factor influencing erythropoiesis. Hemodialysis restores the natural differences in hemoglobin's dissociation characteristics in the arterial and venous circulation.

A review and recommendations for oral chaperone therapy in adult patients with Fabry disease.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and ß or pharmacological oral chaperone migalastat. Migalastat is a low-molecular-mass iminosugar, that reversibly binds to active site of amenable enzyme variants, stabilizing their molecular structure and improving trafficking to the lysosome. Migalastat was approved in the EU in 2016 and is an effective therapy in the estimated 35-50% of all patients with FD with amenable GLA gene variants. This position statement is the first comprehensive review in Central and Eastern Europe of the current role of migalastat in the treatment of FD. The statement provides an overview of the pharmacology of migalastat and summarizes the current evidence from the clinical trial program regarding the safety and efficacy of the drug and its effects on organs typically involved in FD. The position paper also includes a practical guide for clinicians on the optimal selection of patients with FD who will benefit from migalastat treatment, recommendations on the optimal selection of diagnostic tests and the use of tools to identify patients with amenable GLA mutations. Areas for future migalastat clinical research have also been identified.