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Introduction Roxadustat is an orally administered hypoxia-inducible factor prolyl hydroxylase inhibitor being developed for the treatment of anemia of chronic kidney disease (CKD). This European, phase 3, randomized, open-label, active-controlled study investigated efficacy and safety of roxadustat in patients with end-stage kidney disease on dialysis for at least 4 months. Methods Patients were randomized to switch from an erythropoiesis-stimulating agent (ESA) (epoetin alfa or darbepoetin alfa) to roxadustat three times/week or to continue their previous ESA. Roxadustat and ESA doses were adjusted to maintain hemoglobin within 10.0–12.0 g/dL during the treatment period (day 1 up to 52–104 weeks). Primary endpoints were hemoglobin change from baseline (CFB) to the average of weeks 28–36 without rescue therapy and hemoglobin CFB to the average of weeks 28–52 regardless of rescue therapy. Treatment-emergent adverse events (TEAEs) were assessed descriptively. Results Of 1081 screened patients, 836 were randomized and received treatment (roxadustat, n = 415; ESA, n = 421). The least squares means (95% CI) of the treatment difference (roxadustat − ESA) for hemoglobin CFB to weeks 28–36 (without rescue therapy) and CFB to weeks 28–52 (regardless of rescue therapy) were 0.235 (0.132, 0.339) g/dL and 0.171 (0.082, 0.261) g/dL, respectively, demonstrating non-inferiority of roxadustat to ESA (non-inferiority margin of − 0.75 g/dL). The proportions of patients who achieved target hemoglobin without rescue therapy during weeks 28–36 were 84.2% (roxadustat) and 82.4% (ESA). Roxadustat was superior to ESA in decreasing LDL cholesterol from baseline to the average of weeks 12–28. Serious TEAEs occurred in 50.7% (roxadustat) and 45.0% (ESA) of patients. Common TEAEs in both treatment groups included hypertension, arteriovenous fistula thrombosis, headache, and diarrhea. Conclusion Roxadustat was non-inferior to ESAs in maintaining hemoglobin levels in this cohort of patients with anemia of CKD on dialysis for at least 4 months who were previously treated with ESAs. Observed TEAEs were consistent with previous studies. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01904-6.

Introduction This integrated phase 3 analysis examined efficacy and cardiovascular safety for roxadustat vs erythropoiesis-stimulating agents (ESAs) in dialysis-dependent patients. Methods Efficacy and safety results from four phase 3, randomized, open-label studies comparing roxadustat to ESAs (PYRENEES, SIERRAS, HIMALAYAS, ROCKIES) in dialysis-dependent patients with anemia of chronic kidney disease (CKD) were evaluated by study, pooled population and in two subgroups: incident dialysis and stable dialysis. The primary efficacy endpoint per study was hemoglobin change from baseline (CFB) to weeks 28–36 using least-squares mean difference (LSMD) without rescue therapy. Pooled safety endpoints included time to major adverse cardiovascular event (MACE; myocardial infarction, stroke, and all-cause mortality [ACM]) and MACE+ (MACE plus congestive heart failure or unstable angina requiring hospitalization), ACM, and treatment-emergent adverse events (TEAEs). MACE and MACE+ were evaluated for non-inferiority at 1.8 and 1.3 margins using hazard ratios (HRs) and 95% confidence intervals (CIs). TEAEs were descriptively summarized. Results In total, 4714 patients were randomized (2354 roxadustat; 2360 ESA). Hemoglobin CFB to weeks 28–36 achieved non-inferiority for roxadustat vs ESA in each study. Roxadustat was non-inferior to ESA for risks for MACE and MACE+ in the entire cohort (MACE: HR 1.09, 95% CI 0.95–1.26; MACE+ : HR 0.98, 95% CI 0.86–1.11) and similar to the incident dialysis and stable dialysis subgroups; ACM results were consistent with MACE and MACE+ (HR 1.13, 95% CI 0.95–1.34). TEAEs were generally comparable between groups. Conclusion Roxadustat improved hemoglobin similarly to ESA while demonstrating comparable cardiovascular and overall safety profiles in a wide spectrum of dialysis-dependent patients with anemia of CKD. Roxadustat represents an oral alternative to ESAs for achieving a target hemoglobin for anemia of CKD in dialysis-dependent patients. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01903-7.

Background Roxadustat is an orally active hypoxia-inducible factor prolyl hydroxylase inhibitor for the treatment of chronic kidney disease (CKD) anemia. Methods This Phase 3, multicenter, randomized, double-blind, placebo-controlled study examined patients with Stages 3–5 CKD, not on dialysis (NCT01887600). Patients were randomized (2:1) to oral roxadustat or placebo three times weekly for 52–104 weeks. This study examined two primary efficacy endpoints: European Union (European Medicines Agency)—hemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that increased from baseline (BL) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or ≥2.0 g/dL in patients with BL Hb ≤8.0 g/dL, without rescue therapy, during the first 24 weeks of treatment; US Food and Drug Administration—change in Hb from BL to the average Hb level during Weeks 28–52, regardless of rescue therapy. Secondary efficacy endpoints and safety were examined. Results A total of 594 patients were analyzed (roxadustat: 391; placebo: 203). Superiority of roxadustat versus placebo was demonstrated for both primary efficacy endpoints: Hb response [odds ratio = 34.74, 95% confidence interval (CI) 20.48–58.93] and change in Hb from BL [roxadustat – placebo: +1.692 (95% CI 1.52–1.86); both P, Graphical Abstract

Background and Aims Randomised clinical trials evaluating anaemia correction using erythropoietin-stimulating agents (ESAs) in chronic kidney disease (CKD) patients have demonstrated an association between ESA use and increased risk of cardiovascular (CV) complications and mortality. Although the mechanism for this increased risk remains unclear, possibilities include rapid rates of rise (ROR) in haemoglobin (Hb), exposure to high ESA dose and dose escalation, a high Hb target range, and off-target effects of ESAs. Thus, current recommendations generally state that Hb levels should be maintained between 10 and 12 g/dL. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor (HIF-PHI), is used for the treatment of anaemia of CKD; roxadustat stimulates endogenous production of erythropoietin and enhances iron availability, thereby supporting red blood cell production. In this pooled analysis, we explored the relationship between 1) achieved Hb levels and 2) preliminary data for ROR of Hb and subsequent incidence rates of CV events in non–dialysis-dependent (NDD) CKD patients who received roxadustat. Method We analysed pooled data from four phase 3 studies in NDD patients (placebo-controlled: ALPS, ANDES, OLYMPUS; ESA-controlled: DOLOMITES) with anaemia of CKD who received any dose of roxadustat. The reported events occurred during the treatment period and within 7 days of the last dose of roxadustat. Incidence rates of adjudicated major adverse CV events (MACE: all-cause mortality [ACM], myocardial infarction, and stroke), MACE+ (MACE plus heart failure and unstable angina requiring hospitalisation), and ACM were examined relative to 1) most recent Hb level before the event and 2) the preliminary data for ROR of Hb within the 4 weeks of treatment immediately prior to the event. Results Overall, 2709 patients were randomised and received roxadustat. Incidence rates of MACE, MACE+, and ACM were 3- or 4-fold higher in patients with lower reported Hb levels (Hb 2 g/dL in Hb within the 4-week period prior to the event compared to those with a change of ≤2 g/dL within the same period (Table). However, it should be noted that patient-exposure years (PEY) were low for the subgroup of patients with ROR >2 g/dL (∼3.3% of overall PEY), and patients with a decreasing Hb were included in the ≤2 g/dL/4 weeks subgroup. Conclusion In this analysis of roxadustat-treated patients with NDD CKD, incidence rates of MACE, MACE+, and ACM were lower in patients who achieved target Hb levels of 10-12 g/dL compared with patients who achieved Hb

Background and Aims Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, induces a coordinated erythropoietic response by increasing endogenous erythropoietin levels and improving iron metabolism. This analysis was performed to examine the consistency of efficacy and cardiovascular safety results for roxadustat vs placebo or darbepoetin alfa (DA) in patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD). Method Results from three phase 3, double-blind studies comparing roxadustat with placebo (ALPS, ANDES, OLYMPUS) with anaemia and stage 3-5 NDD CKD were pooled and assessed for consistency with results of an open-label study comparing roxadustat with DA (DOLOMITES) in predominantly European patients. The primary efficacy endpoint was haemoglobin (Hb) response, defined as (a) Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or (b) Hb CFB by ≥2.0 g/dL in patients with Hb ≤8.0 g/dL irrespective of and without rescue therapy for placebo-controlled (assessed for superiority) and DA-controlled (assessed for non-inferiority) studies, respectively. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 using least squares mean difference (LSMD) without rescue therapy. The key safety endpoints of major adverse cardiovascular event (MACE, comprising death, myocardial infarction, and stroke) and MACE+ (MACE plus hospitalization with heart failure or unstable angina) were adjudicated in all studies. MACE and MACE+ for roxadustat vs placebo or DA were compared in the intention-to-treat sample using a Cox proportional hazards model. Results In total, 4886 patients were randomised in placebo-controlled (2386 roxadustat, 1884 placebo) and DA-controlled (323 roxadustat, 293 DA) studies. Baseline characteristics of patients treated with roxadustat vs placebo and roxadustat vs DA were similar: baseline Hb (placebo, 9.10 vs 9.10 g/dL; DA, 9.55 vs 9.55 g/dL) and iron repletion (placebo, 59.9% vs 59.8%; DA, 56.3% vs 51.9%). Roxadustat was superior to placebo for Hb response without rescue therapy (80.2% vs 8.7%; difference of proportion [DOP], 71.50%; 95% CI, 69.40-73.51) and noninferior to DA (89.5% vs 78.0%; DOP, 11.51%; 95% CI, 5.66-17.36). Mean Hb CFB (Weeks 28-36) achieved superiority in pooled analysis vs placebo (LS mean, 1.91 vs 0.14; LSMD, 1.77; 95% CI, 1.69-1.84; P Conclusion Roxadustat corrected Hb more effectively than placebo and comparably to DA in patients with anaemia and stage 3-5 NDD CKD. Cardiovascular safety was comparable between roxadustat and DA and placebo.

Background and Aims Roxadustat regulates erythropoiesis and iron metabolism through hypoxia-inducible factor prolyl hydroxylase inhibition. This regional analysis evaluated efficacy and safety for roxadustat versus placebo/darbepoetin alfa (DA) in NDD CKD patients with anaemia. Method Results from three, double-blind phase 3 studies comparing roxadustat to placebo (ALPS, ANDES, OLYMPUS) in patients with anaemia and stage 3-5 NDD CKD were pooled and evaluated alongside results of an open-label study comparing roxadustat to DA (DOLOMITES) in the same population. Efficacy outcomes were compared in three regions (Europe, US, and other) in placebo-controlled studies (PCS) and two regions (Western Europe/Israel and Central/Eastern Europe) in the DA-controlled study (DCS). The primary efficacy endpoint in Europe was haemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb >8.0 g/dL or as CFB ≥2.0 g/dL in patients with Hb ≤8.0 g/dL. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 without rescue therapy (intravenous iron, red blood cell [RBC] transfusion, or erythropoiesis-stimulating agent [ESA] for PCS; RBC transfusion or ESA [roxadustat only] for DCS). Incidence of treatment-emergent adverse events (TEAEs) was summarised descriptively in two regions in PCS (Europe and non-Europe) and two regions in DCS (Western Europe/Israel and Central/Eastern Europe). Results A total of 4886 patients were randomised (2709 roxadustat; 1884 placebo; 293 DA). A significantly greater proportion of patients in all regions who received roxadustat had a Hb response without rescue therapy vs placebo (Europe: 77.9% vs 16.5%, difference of proportion [DOP] 61.4%, 95% CI: 56.5-66.2; US: 75.4% vs 8.3%, DOP 67.2%, 95% CI: 62.7-71.6; and other: 83.4% vs 5.5%, DOP 78.0%, 95% CI: 75.4-80.5) and a numerically greater proportion in both regions vs DA (Western Europe/Israel: 93.9% vs 83.5%, DOP 10.4%, 95% CI: 1.2-19.6; Central/Eastern Europe: 86.5% vs 75.4%, DOP 10.9%, 95% CI: 3.6-18.3). Mean Hb CFB was significantly greater with roxadustat vs placebo in Europe (2.01 vs 0.37 g/dL, LSMD 1.70, 95% CI: 1.55-1.84), US (1.80 vs 0.21 g/dL, LSMD 1.67, 95% CI: 1.53-1.82), and other (1.80 vs 0.06 g/dL, LSMD 1.77, 95% CI: 1.64-1.89) (all P Conclusion In patients with anaemia and stage 3-5 NDD CKD, roxadustat was more effective than placebo for correcting Hb and generating Hb response without rescue therapy in Europe, the US, and other countries. It was similarly effective as DA for correcting Hb and generating a Hb response without rescue therapy in Western Europe/Israel and Central/Eastern Europe. The incidence of select TEAEs was comparable and relatively low in all regions.

Introduction After kidney transplantation (KTx) in patients with diagnosed cancers, calcineurin inhibitor tacrolimus (TAC) is replaced by sirolimus or everolimus (EV). Objective The objective of the study was to compare the lipid metabolism parameters, KTx function, and glucose and hemoglobin (Hgb) levels in patients treated with EV to those on TAC. Material and Methods The retrospective study included 114 patients: 54 (17 women and 37 men) aged 57.6 years (18-77 years) treated with EV and 60 (18 women and 42 men) aged 49.6 years (20-77 years) treated with TAC as a control group. Their total cholesterol (TC), triglycerides (TG), fasting glucose (FG), serum creatinine (SCr), Hgb, and estimated glomerular filtration rate (eGFR) were assessed. In the patients treated with EV, the above values were evaluated before conversion, as well as 12 and 24 months following the switch and were evaluated once in the group treated with TAC. Results In the EV-treated group, the mean preconversion values after 12 and 24 months were as follows: TC 5.06, 6.59, and 5.98 mmol/L; TG 1.90, 2.48, and 2.20 mmol/L; FG 94.95, 97.85, and 104.05 mg/dL; SCr 1.46, 1.44, and 1.56 mg/dL; Hgb 12.46, 12.83, and 13.36 g/dL; and eGFR 50.3, 50.6, and 50.5 mL/min/1.73 m2. In the patients on TAC, the authors obtained the following values: TC 4.6 mmol/L; TG 1.87 mmol/L; glucose 104.13 mg/dL; SCr 1.51 mg/dL; Hgb 13.96 g/dL; and eGFR 56.6 mL/min/1.73 m2. Conclusions After conversion from TAC to EV, increased values of TC and TG were observed after 1 year, while the increased values of TC, TG, SCr, Hgb, and FG were observed after 2 years.

Introduction Post-transplant lymphoproliferative disorder (PTLD) is a serious, life-threatening complication in organ transplant patients receiving immunosuppressive therapy. The risk factors include Epstein-Barr virus infection and a cumulative dose of the immunosuppression. Case Report We present a 5-year follow-up case of a 28-year-old patient with PTLD in the gastrointestinal tract. In the ninth month after kidney transplant, the patient was hospitalized for pain in the abdomen and diarrhea. Physical examination demonstrated tenderness in the area of the cecum, and colonoscopy revealed ulcerations in the large intestine. Polymorphic lymphoma (PTLD) was found in the collected samples. The patient received monotherapy treatment with anti-CD20 antibodies, resulting in complete remission of disease, confirmed by computed tomography scan and colonoscopy. Conclusion PTLD may have a different clinical course and should be considered in the differential diagnosis of patients after organ transplant.

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.

Introduction: The diagnosis and classification of chronic kidney disease (CKD) are based on the glomerular filtration rate value. The simplest way to evaluate glomerular filtration rate is to estimate it based on serum creatinine concentration using one of many specific mathematical formulas. None of the formulas created for this purpose are perfect. Differences in eGFR values are frequently observed in specific stages of chronic kidney disease by KDIGO classification based on different formulas. Aim: The aim of the study is to compare the eGFR value in patients previously diagnosed with CKD treated in the Outpatient Nephrology Unit of the University Hospital in Krakow using the selected formulas. Material/Methods: The study was performed in a group of 882 patients (392 women, 490 men) aged 65.0 ± 14.8 years. GFR values were estimated using Bjornsson, the abbreviated MDRD, and CKD-EPI formulas. These values were then compared according to chronic kidney disease stage and age groups: above and below 60 years. Results: The mean eGFR value was for Bjornsson formula- 47.2 ± 21.1 ml/min/1.73m2, abbreviated MDRD formula- 38.8 ± 15.2 ml/min/1.73m2, and CKD-EPI formula- 37.7 ± 15.9 ml/min/1.73m2. There was a large concordance in eGFR values obtained using the CKD-EPI and abbreviated MDRD formulas in every stage of chronic kidney disease and in both age groups. The Bjornsson formula significantly increased the number of patients in early stages of CKD, G1 - 33 vs 2 (abbreviated MDRD) and 6 (CKD-EPI), G2- 186 vs 70 (abbreviated MDRD) and 69 (CKD-EPI). Conclusions: CKD-EPI and abbreviated MDRD formulas have a similar usefulness in GFR value estimation in patients with diagnosed chronic kidney disease. Lower eGFR values achieved using abbreviated MDRD formula and CKD-EPI equation in comparison with Bjornsson’s formula may result in an increased number of patients diagnosed with CKD.

In Doppler echocardiography, testing left ventricular outflow tract (LVOT) gradient in the supine position (as is done in everyday practice) does not reflect the pathophysiology of this dynamic abnormality during the daily activities that trigger the symptoms (eg, syncope). LVOT obstruction is a dynamic phenomenon, strongly dependent on the left ventricular cavity size, geometric configuration of hypertrophy, load variability, contractility, and mitral apparatus abnormalities. LVOT gradient may develop not only in hypertrophic cardiomyopathy but also in various heart diseases. Recent investigations show that LVOT gradient should be measured also in the standing position. Here, we report the case of patient after renal transplantation, who developed LVOT gradient during orthostatic test. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:616-620, 2017.

Introduction: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end-stage renal disease (ESRD). There is an ongoing search for novel biomarkers of CV disease in this population. Objectives: We aimed to investigate the associations of matrix proteoglycans (PGs) and glycosaminoglycans (GAGs), collagen, and arterial calcifications with selected serum and plasma markers of endothelial dysfunction, inflammation, oxidative stress, and bone turnover in patients with ESRD. Patients and methods: We enrolled 47 adult patients (32 men) with stage 5 CKD. The following parameters were investigated: fibrinogen, soluble thrombomodulin (sTM), plasminogen activator inhibitor 1 (PAI-1), stromal cell-derived factor 1α (SDF-1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high-sensitivity C-reactive protein (hs-CRP), ferric reducing ability of plasma, 2,2-diphenyl-1-picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin-A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor β (TGF-β), hepatocyte growth factor, secreted protein acidic and rich in cysteine, as well as matrix metalloproteinase 2. Radial artery specimens were stained with alizarin red for calcifications, alcian blue for PGs and GAGs, and sirius red for collagen. Results: We observed positive correlations between PG and GAG, collagen, and calcification staining. The most intense (grade 3) alcian blue staining was significantly correlated with diabetes as well as higher levels of Ca×Pi product, hs-CRP, fibrinogen, SDF-1α, PAI-1, and sTM. However, PAI-1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca×Pi product, and hs-CRP levels. Conclusions: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF-1α, PAI-1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers. biomarkers end‑stage renal disease glycosaminoglycans plasminogen activator inhibitor 1 proteoglycans

Purpose The high prevalence of cardiovascular morbidity and mortality among patients with chronic kidney disease (CKD) is observed especially in those undergoing dialysis. Osteoprotegerin (OPG) and its ligands, receptor activator of nuclear factor kappa-B ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) have been associated with cardiovascular complications. Our aim was to study their role as cardiovascular risk factors in stage 5 CKD patients. Patients and methods OPG, RANKL and TRAIL concentrations were measured in 69 hemodialyzed CKD patients and 35 healthy volunteers. In CKD patients, cardiovascular dysfunction was assessed with aortic pulse wave velocity (AoPWV), carotid artery intima-media thickness (CCA-IMT), coronary artery calcium score (CACS) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) serum concentrations. Cardiovascular and overall mortality data were collected during a 7-years follow-up. Results OPG plasma concentrations were higher in CKD patients comparing to controls. Total soluble RANKL was lower and OPG/RANKL ratio higher in patients. Soluble TRAIL concentrations did not differ between the groups and OPG/TRAIL ratio was higher in CKD patients. OPG and OPG/TRAIL positively predicted long-term mortality (all-cause and cardiovascular) in CKD patients. OPG positively correlated with AoPWV, CCA-IMT and NT-proBNP whereas OPG/TRAIL with AoPWV and NT-proBNP. Described relationships were independent of classical and non-classical cardiovascular risk factors, with exception of age. Conclusions Our study confirmed the role of OPG as a biomarker of cardiovascular dysfunction and a predictor of mortality in stage 5 CKD. OPG/TRAIL ratio can be proposed as a predictor of cardiovascular dysfunction and mortality.

BACKGROUND Immunosuppressive medications often cause posttransplant hyperlipidemia. The effects of cyclosporine (CsA) and tacrolimus (Tac) on lipid profile is well-known; however, there are very few studies related to the effect of these immunosuppressants on fatty acids (FA) of phosholipids fraction (PL) in renal transplant recipients (RTR). We sought to analyze the FA profile in PL fraction of RTR treated with Tac or CsA. METHODS The study included 65 renal transplant patients on CsA (n = 24, group I) or Tac (n = 41, group II), and 14 healthy controls. Individual serum FA concentrations were measured by gas chromatography. Chemstation software was used to analyze the data. RESULTS No differences between studied groups and controls were noted for monounsaturated FA, polyunsaturated n-3 FA (PUFA n-3), PUFA n-6, or the ratio of PUFA n-6 to PUFA n-3. The following mean values of FA were significantly higher in the CsA-RTR and Tac-RTR as compared with controls: total FA (P < .01 in both cases), saturated FA (SFA; P < .02 in both cases), C12 (P < .003 in both cases), C18 (P < .003 in both cases), and C18:2 (P < .01 for CsA RTR; P < .02 for Tac RTR). No differences between the measurements in patients on CsA and in patients on Tac were noticed. Significant correlation between SFA and eGFR was observed only in the CsA RTR group (P

Background: Peritoneal dialysis (PD) solutions with reduced sodium content may have advantages for hypertensive patients; however, they have lower osmolarity and solvent drag, so the achieved Kt/V-urea may be lower. Furthermore, the increased transperitoneal membrane sodium gradient can influence sodium balance with consequences for blood pressure (BP) control.Study Design: Prospective, randomized, double-blind clinical trial to prove the noninferiority of total weekly Kt/V-urea with low-sodium versus standard-sodium PD solution, with the lower confidence limit above the clinically accepted difference of 0.5. Setting & Participants: Hypertensive patients (1 antihypertensive drug, including diuretics, or office systolic BP 130 mm Hg) on continuous ambulatory PD therapy from 17 sites.Intervention: 108 patients were randomly assigned (1:1) to 6-month treatments with either low-sodium (125 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 338-491 mOsm/L) or standard-sodium (134 mmol/L of sodium; 1.5%, 2.3%, or 4.25% glucose; osmolarity, 356-509 mOsm/L) PD solution.Outcomes: Primary end point: weekly total KtNurea; secondary outcomes: BP control, safety, and tolerability. Measurements: Total KtNurea was determined from 24-hour dialysate and urine collection; BP, by office measurement.Results: Total Kt/Vurea after 12 weeks was 2.53 +/- 0.89 in the low -sodium group (n = 40) and 2.97 +/- 1.58 in the control group (n = 42). The noninferiority of total KtNurea could not be confirmed. There was no difference for peritoneal KtNurea (1.70 +/- 0.38 with low sodium, 1.77 +/- 0.44 with standard sodium), but there was a difference in renal KtNurea (0.83 +/- 0.80 with low sodium, 1.20 +/- 1.54 with standard sodium). Mean daily sodium removal with dialysate at week 12 was 1.188 g higher in the low-sodium group (P Limitations: Broader variability of study population than anticipated, particularly regarding residual kidney function.Conclusions: The noninferiority of the low -sodium PD solution for total Kt/Vurea could not be proved; however, it showed beneficial clinical effects on sodium removal and BP. Am J Kidney Dis. 67(5):753-761. 2016 Fresenius Medical Care. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.orgIlicenses/by-nc-nd14.01).

Glomerular filtration rate plays a key role in the diagnosis of chronic kidney disease (CKD). In everyday practice GFR is estimated using equations based on serum creatinine. Commonly used abbreviated MDRD formula is not very precise in patients with mildly impaired renal function, underestimating eGFR when greater than 60 ml/min/1.73 m2. CKD-EPI formula, recommended by KDIGO, might be a good alternative in this situation. The aim of the study was to compare the prevalence of consecutive stages of CKD in the group of patients from Emergency Department having calculated eGFR according MDRD and CKD-EPI formulasThe retrospective study was performed in the group of 1,452 patients (762 women and 690 men aged 57.4 years ± 19.8 years). Estimated GFR (eGFR) was calculated based on MDRD and CKD-EPI formulas and the obtained results were analyzed according patients location in the consecutive group of CKD, used formulas, sex and age.The mean values of eGFR for both formulas were similar and for MDRD was 68.6 ± 22.3 ml/min/ 1.73 m2 while for CKD-EPI 69.18 ± 24.4 ml/ min/1.73 m2. The highest differences were observed in the early stages of CKD where the calculation of eGFR based on CKD-EPI vs MDRD formula gives an increase of population in stage G1 of CKD by 5.7% (342 vs 241 persons) and reduction by 7.8% (625 vs 737) in the stage G2.Both formulas have the similar value in the estimation of CKD. The differences concerning mainly G1 and G2 stages.

Acute kidney injury (AKI) is a frequent, serious and sometimes unreversable complication in patients with cardiovascular disease. The aim of the study was to evaluate the frequency of recovery renal function and commorbidities in patients with AKI complicating severe cardiovascular diseases.A retrospective analysis of 246 patients (157 men and 89 women aged 67.9 ± 14.8 years) with AKI in the course of severe cardiovascular diseases, hospitalized in intensive care units and words of nephrological profile in years 2000-2011 were performed. Analysis was based on surveys data collected by regional consultant on the field of nephrology. Based on these data precise information about recovery of renal function was present in 143 documents.In the studied group of 143 patients recovery of renal function was observed in 39 subjects (27.3%). Kidney dysfunction before AKI was observed in 116 patients from the whole study group (47.2%). Such commorbidities like: myocardial infarction, sudden cardiac arrest, diabetes, arterial hypertension, chronic obstructive pulmonary disease or performed operations and grade of biochemical disturbances had no significant influence on recovery of renal function. Complications observed during AKI and anemia negatively influenced on recovery of renal function (p0.001 and p = 0.007). Patients staying longer at hospital has more frequent recovery of renal function (p = 0.014).Probability of renal function recovery in patients with AKI in the course of severe cardio-vascular complications is low.

INTRODUCTION Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases.

INTRODUCTION Medial arterial calcification is common in patients with chronic kidney disease (CKD) and is considered a risk factor for morbidity and mortality. OBJECTIVES We aimed to evaluate the correlation between asymmetric dimethylarginine (ADMA) levels, radial artery calcification, and common carotid artery intima-media thickness (CCA‑IMT). PATIENTS AND METHODS The study included 51 patients with CKD, in whom an arteriovenous fistula for hemodialysis access was created to collect radial artery samples for a histological examination, and 33 healthy volunteers, in whom the reference concentrations of ADMA were assessed. The concentrations of creatinine, albumin, calcium, phosphate, fibroblast growth factor 23, osteoprotegerin (OPG), osteopontin (OPN), osteocalcin, secreted protein acidic and rich in cysteine, interleukin 6, interleukin 18, pentraxin 3, stromal cell‑derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP‑2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA‑IMT was assessed by ultrasonography. RESULTS Patients with CKD had higher ADMA levels than controls. Patients with ADMA levels above the median were older, had higher levels of phosphate, fibroblast growth factor 23, OPG, OPN, PTX3, sTNFRII, MMP‑2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log‑transformed (log)sTNFRII, MMP‑2, and SDF1α levels were independent predictors of log(ADMA). Patients with calcifications had higher ADMA levels. A similar correlation was observed between SDF1α and alizarin red staining grades 1 to 3. In logistic regression, ADMA levels positively predicted the presence of calcifications independently of age, hemodialysis status, Framingham risk score, and PTX3. CONCLUSIONS Circulating ADMA levels indicate medial arterial calcification in patients with CKD.

Diabetes mellitus and hyperlipidemia are frequently observed after organ transplantation. It is known that in these disorders the fatty acid metabolism is impaired. The aim of this study was to compare the fatty acid profile in the heart and renal transplant recipients who developed metabolic disorders since there is no such research available.The study included 55 patients treated with tacrolimus (Tac) after heart (n = 14; mean age: 60.4 ± 9.1) or renal (n = 41; mean age: 51 ± 13) transplantation. Diabetes and hyperlipidemia was present in 35.7% and 28.5% of heart transplant recipients, and 19.5% and 41% of renal transplant recipients. Concentrations of fatty acid in phospholipids fraction in serum were measured by gas chromatography.The concentration of C20:5 fatty acid was lower in heart transplant recipients, as compared to renal transplant recipients (p = 0.001), whereas the level of C20+C18:3 fatty acid and the ratio of n-6/n-3 was higher (p = 0.01; p = 0.03, respectively). The observed differences were not related to metabolic disorders. Negative correlation between C16:1 and eGFR was seen in heart transplant recipients (p = 001). In renal transplant recipients with metabolic disorders, the concentration of C20:5 was correlated positively whereas the n-6/n-3 ratio was correlated negatively with eGFR (p 0.001, p = 0.01, respectively). Hyperlipidemic renal transplant recipients had higher concentration of C20:2 (p = 0.02), C20:4 (p = 0.05), n-6 (0.04) and total fatty acid (p = 0.01) than patients without metabolic disorders.The fatty acid profile differs depending on the transplanted organ, but the differences are not related to the metabolic disorders. The role of fatty acid in kidney function varies between heart transplant recipients and renal transplant recipients and depends on type of fatty acid.

A retrospective study was conducted among 498 patients with urinary tract infections (UTI) referred to our department from January 2013 to December 2015. This study was performed to evaluate the etiology of UTI and the antibiotic susceptibility profile of Escherichia coli ( E. coli ) as the main etiological factor in different age groups. Urine samples were examined using standard microbiological methods. Three hundred sixty-three samples (72.9%) were identified as E. coli , of which 29 (8.0%) can produce extended-spectrum β-lactamases (ESBL). E. coli was highly sensitive to imipenem (100.0%), gentamicin (91.0%), nitrofurantoin (89.4%), amikacin (88.2%), piperacillin/ tazobactam (87.0%) and cephalosporins (79.7-89.5%). Low sensitivity was found in relation to fluoroquinolones (60.3-70.4%). E. coli was least sensitive to ampicillin (30.2%) and amoxicillin/clavulanic acid (49.9%). We observed a significant fall in susceptibility level to piperacillin/tazobactam (68.4% vs. 88.8%; p = 0.017), amikacin (61.1% vs. 90.7%; p = 0.001), gentamicin (70.0% vs. 93.2%; p = 0.002), cefalexin (41.2% vs. 83.3%; p < 0.001), cefotaxime (63.6% vs. 89.4%; p = 0.002), ceftazidime (61.9% vs. 85.6%; p = 0.008), cefepime (73.7% vs. 91.1%; p = 0.025), ciprofloxacin (54.1% vs. 72.2%; p = 0.024) and norfloxacin (40.5% vs. 62.5%; p = 0.011) among patients with catheter-associated UTI (CAUTI) compared to those with non-CAUTI. A similar susceptibility profile was observed between different age groups. In the longevity, E. coli showed a higher sensitivity to cephalosporins than in the young-old group. E. coli susceptibility to fluoroquinolones was low, which excludes them as a first-line drug in our department. Nitrofurantoin may be used as an alternative drug to carbapenems. Monitoring of susceptibility pattern is of great importance. A retrospective study was conducted among 498 patients with urinary tract infections (UTI) referred to our department from January 2013 to December 2015. This study was performed to evaluate the etiology of UTI and the antibiotic susceptibility profile of Escherichia coli (E. coli) as the main etiological factor in different age groups. Urine samples were examined using standard microbiological methods. Three hundred sixty-three samples (72.9%) were identified as E. coli, of which 29 (8.0%) can produce extended-spectrum β-lactamases (ESBL). E. coli was highly sensitive to imipenem (100.0%), gentamicin (91.0%), nitrofurantoin (89.4%), amikacin (88.2%), piperacillin/ tazobactam (87.0%) and cephalosporins (79.7–89.5%). Low sensitivity was found in relation to fluoroquinolones (60.3–70.4%). E. coli was least sensitive to ampicillin (30.2%) and amoxicillin/clavulanic acid (49.9%). We observed a significant fall in susceptibility level to piperacillin/tazobactam (68.4% vs. 88.8%; p = 0.017), amikacin (61.1% vs. 90.7%; p = 0.001), gentamicin (70.0% vs. 93.2%; p = 0.002), cefalexin (41.2% vs. 83.3%; p < 0.001), cefotaxime (63.6% vs. 89.4%; p = 0.002), ceftazidime (61.9% vs. 85.6%; p = 0.008), cefepime (73.7% vs. 91.1%; p = 0.025), ciprofloxacin (54.1% vs. 72.2%; p = 0.024) and norfloxacin (40.5% vs. 62.5%; p = 0.011) among patients with catheter-associated UTI (CAUTI) compared to those with non-CAUTI. A similar susceptibility profile was observed between different age groups. In the longevity, E. coli showed a higher sensitivity to cephalosporins than in the young-old group. E. coli susceptibility to fluoroquinolones was low, which excludes them as a first-line drug in our department. Nitrofurantoin may be used as an alternative drug to carbapenems. Monitoring of susceptibility pattern is of great importance.

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

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.

Background Chronic refractory hypotension (IDH, intradialytic hypotension) is a rare but serious problem encountered in patients on hemodialysis. Patients with chronic hypotension are often disqualified by transplant teams from renal transplantation. This is due to the possibility of an enormous risk of ischemic complications. Case presentation We describe a 44-year old female patient with severe refractory hypotension (mean BP 60/30 mmHg, the lowest 48/28 mmHg), which appeared after bilateral laparoscopic nephrectomy of the infected kidneys. The kidney transplantation from a deceased donor, with infusion of the two pressor amines (dopamine, dobutamine) was performed without technical complications and the blood pressure measurements were 100–120/70–80 mmHg. The immunosuppression regimen was tacrolimus (TAC) + mycophenolate mophetil (MMF) and steroids (GS). Pressor amines were discontinued on the 18th day after the transplantation. Because of delayed graft function, 4 hemodialysis treatments were performed. The patient was discharged from the hospital on the 22nd day with good function of the transplanted kidney (the concentration of serum creatinine 117 μmol/l). During one-year follow-up, the patient has been remaining stable with a very good graft function (serum creatinine 84 μmol/l) and normal blood pressure (115/70 mmHg). Conclusions Proper preparation and adequate perioperative treatment allowed for safely performing kidney transplantation in the patient with severe IDH.

Introduction Long -term use of immunosuppressant therapy makes kidney transplant recipients particularly susceptible to infections and skin cancers. Objectives The aim of the study was to evaluate the type and location of nonmelanoma skin cancers (NMSCs) in patients after kidney transplantation. Patients and methods The study included 486 patients (296 men and 190 women; mean age, 46.1 ±13.1 years) after deceased -donor kidney transplantation, most of whom received triple immunosuppressive therapy. Patients underwent skin examination. All suspicious lesions were thoroughly described in terms of their type, size, and location. Only patients with histologically confirmed malignancy were included in the study. Results Of all 486 patients, 25 were diagnosed with 53 NMSCs, including 39 basal cell carcinomas, 13 squamous cell carcinomas, and 1 case of Bowen's disease. The lesions were observed on the face (n = 34), upper limb (n = 8), neck (n = 6), and trunk (n = 5). Conclusions Most NMSCs were located on the sun -exposed areas, emphasizing the effect of ultraviolet radiation on the pathogenesis of skin cancers. The presence of lesions on the skin that had not been exposed to the sun indicates that a physical examination of the entire skin is necessary.

INTRODUCTION Infectious skin lesions are a common complication in renal transplant patients receiving immunosuppressive therapy. OBJECTIVES The aim of this study was to assess the prevalence and factors contributing to the development of viral skin infections in kidney transplant patients. PATIENTS AND METHODS The study included 486 patients, 296 men (60.9%) and 190 women (39.1%), aged 46.1 ±13.1 years, 74.3 ±52.1 months post‑transplantation, who remained mostly on triple immunosuppressive therapy. All skin lesions detected during the dermatological examination were described in detail, and the type, size, exact location, dependence on age, sex, and the used immunosuppressive therapy were established. Patients were followed for 5 years. RESULTS Infectious skin lesions of viral origin were diagnosed in 189 of 486 patients (38.9%). The most frequent infections were viral warts (38.5%), which were more common in older patients (47.6 vs. 45.0 years, P

INTRODUCTION Hepatocyte growth factor (HGF) is a regenerative protein involved in tissue protection and endothelial repair in response to injury. OBJECTIVES The aim of the study was to assess the effect of increased HGF levels on total and cardiovascular (CV) mortality in patients on peritoneal dialysis (PD) during 6‑year follow‑up. PATIENTS AND METHODS The study included 55 patients (mean age, 53 years; median duration of PD, 24 months). The ejection fraction (EF) and calcium score (CaSc) were measured. White blood cell (WBC) count and albumin, calcium (Ca), phosphorus (Pi), intact parathormone (iPTH), and high‑sensitivity C‑reactive protein (hsCRP) levels were measured. Serum levels of HGF, interleukin (IL) 6, and IL‑18 were determined using enzyme‑linked immunosorbent assays. RESULTS Of all patients, 45% died within 6 years, including 80% from CV complications. HGF significantly correlated with the total (hazard ratio [HR], 1.97; P = 0.03) and CV (HR, 2.04; P = 0.04) mortality in a univariate Cox regression model. This was confirmed by a multiple model including age, dialysis duration, residual renal function (RRF), albumin, Ca × Pi, EF, and CaSc (HR, 2.24; P = 0.02 and HR, 2.58; P = 0.02 for total and CV mortality, respectively). Factors negatively affecting patients' survival included WBC count, hsCRP, IL‑6, and CaSc, while higher albumin levels and EF were associated with longer overall survival. HGF positively correlated with WBC count (r = 0.30, P = 0.01), hsCRP (r = 0.25, P = 0.04), IL‑6 (r = 0.46, P = 0.0004), CaSc (r = 0.29, P = 0.03), and mean arterial pressure (r = 0.25; P = 0.04) and negatively with RRF (r = -0.31, P = 0.02). CONCLUSIONS Increased concentrations of proinflammatory cytokines and an association between HGF levels and CaSc may indicate higher total and CV mortality in patients on PD.

Dialysis treatment, which is one of the methods of renal replacement therapy, is without a doubt one of the milestones in the development of medicine over the last 100 years. The method dates back to 1913, when John Abel, Leonard Rowntree and Bernard Turner of the USA succeeded in developing the first haemodialysis machine and performed the pioneering experiments on dogs. The first human haemodialysis session was performed in Giessen, Germany by Georg Haas in 1924. One year before that, Georg Ganter, also in Germany, performed the first peritoneal dialysis in human. However, it is the Dutch Willem Kolff who, by general consent, takes the credit for being the pioneer of haemodialysis. During the Second World War, he designed his own haemodialysis machine and used it to save the life of his patient with acute renal failure. After the war, another artificial kidney was designed in Lund, Sweden by Nils Alwall and was first used for haemodialysis in 1946. The Lund clinic went on to become one of the major European dialysis centres, where a number of Polish doctors were trained, later transferring their experience onto the Polish ground. The group included Dr Zygmunt Hanicki of the 2nd Department of Internal Medicine at the Medical University in Krakow, who, in the years 1949–57, having received the prototype of the machine from Nils Alwall, published the first Polish papers on haemodialysis treatment followed by the results of the laboratory studies [1, 2] (Figure 1). Fig. 1. Dr Zygmunt Hanicki (1919–95) and a copy of the title page of the first Polish article on the artificial kidney written by him ‘The Artificial Kidney. Possibilities of Application and Attempt to Explain the Mechanism’ published ... The first haemodialysis session in Poland was performed in Poznan in 1958 by the team of Dr Kazimierz Bączyk from the 2nd Department of Internal Medicine headed by Prof. Jan Roguski. The Krakow centre was the fourth dialysis centre to be established in Poland with the first haemodialysis session performed there on 15 June 1962 under the supervision of Assistant Professor Zygmunt Hanicki. Drs Zbylut Twardowski and Przemyslaw Hirszel, Jozef Bogdal, Adam Wiernikowski and the nurse Marcelina Pacut also participated in the session. Although Alwall's machine was the first artificial kidney used in the centre, later, along with its growth, newer haemodialysis machines were introduced to meet the current trends. Moreover, Prof. Hanicki, the Head of the clinic, started the building of an all-new dialysis unit at the Department of Nephrology [3] (Figures 2 and ​and33). Fig. 2. More than 100-year-old building with the first dialysis unit of the Department of Nephrology inside (photo by Janusz Ostrowski). Fig. 3. During one of the first haemodialyses in the 2nd Department of Internal Medicine at the Medical Academy in Krakow. First left: Dr Zygmunt Hanicki, the founder of the centre, nurse Marcelina Pacut, Dr Zuzanna Pączek and Dr Jozef Bogdal ... Following Prof. Hanicki's retirement, his student, Assistant Professor Wladyslaw Sulowicz took over as the Head of the Department to continue the development of the Department of Nephrology which today is one of the largest and most modern centres of nephrology in Poland, providing all kinds of renal replacement therapy on the highest level. Nowadays, the clinic comprises: the Conservative Management Unit, Dialysis Patient Unit, Post-Renal Transplant Unit, Peritoneal Dialysis Unit, Haemodialysis Unit (41 dialysis stations), Intensive Care Unit, operating theatre, Outpatient Department of Nephrology and Post-Renal Transplant Outpatient Clinic, as well as ultrasonography, X-ray, gastroscopy and rehabilitation facilities [4]. The ‘Progress in Nephrology and Transplantation’ Conference and Educational Course by ERA-EDTA held in Krakow on 10–12 May 2012, and attended by renowned Polish and foreign nephrologists was the capstone of the 50 years' activity of the Department of Nephrology at the Collegium Medicum of the Jagiellonian University in Krakow. Juliusz Slowacki theatre was the venue for the Opening Ceremony of the event. The official part included the speeches by Prof. Wladyslaw Sulowicz—the Chief Organizer, Prof. Wojciech Nowak—Vice-Rector for Collegium Medicum at the Jagiellonian University, Prof. Jacek Majchrowski—the President of Krakow, Prof. Raymond Vanholder—the President of ERA-EDTA, Prof. Goce Spasovski—ERA-EDTA Chairman for Continuous Education, Prof. Andrzej Wiecek—ERA-EDTA Secretary and Treasurer, Prof. Marian Klinger—Member of the Board of ERA-EDTA and the National Specialist for Nephrology and Prof. Jacek Manitius—the President of the Polish Society of Nephrology. To complete the official inauguration, the opening lecture titled ‘The Doctor's Mission in Modern Medicine’ was given by Prof. Tomasz Guzik (Figures 4 and ​and55). Fig. 4. Main building of the Jagiellonian University in Krakow, Poland (photo by Janusz Ostrowski). Fig. 5. Title page of the programme of the conference. The first part of the scientific session was of historical and recollective character with the lectures given by doyens of the Polish nephrology: Prof. Franciszek Kokot, Prof. Zofia Wankowicz and Prof. Zbylut Twardowski. The other subjects discussed during the remaining sessions of the first day included disturbances in calcium and phosphate in patients with renal failure (Prof. Goce Spasovski, Prof. Markus Ketteler, Prof. Tilman Drueke and Prof. Michal Myśliwiec), performance of dialysis in elderly patients (Prof. Marian Klinger), obesity-related glomerulopathy (Prof. Andrzej Wiecek), disaster-related complications in nephrology (Prof. Raymond Vanholder), renal replacement therapy in acute renal failure in the course of acute poisoning (Prof. Miroslav Mydlik), dialysis adequacy (Dr James Tattersall), anaemia therapy (Prof. Dimitros Tsakiris) and carnitine system in haemodialysed patients (Prof. Vincenzo Savica) (Figure 6). Fig. 6. Pioneers of dialysis treatment in Poland. First left: Prof. Zofia Wankowicz and Prof. Zbylut Twardowski (photo by Janusz Ostrowski). The first session on the second day of the conference concentrated on renal transplantation with lectures given by Prof. Przemyslaw Hirszel, Dr Paul Harden and Prof. Magdalena Durlik. In the session ‘Meet the Expert’, the current trends in anaemia therapy, new options in dialysis therapy, the methods of Ca-P metabolism control in Chronic Kidney Disease and the ways to increase the number of kidney transplantations were addressed. The chairpersons of the sessions were respectively: Prof. Jolanta Malyszko, Prof. Ryszard Gellert, Prof. Zbigniew Hruby and Prof. Ryszard Grenda. The speakers giving lectures in the last session included: Prof. Boleslaw Rutkowski (Epidemiology of Chronic Kidney Disease), Prof. Guido Bellinghieri (Pain and Quality of Life in Uraemic Patients), Prof. Andrzej Ksiązek (Hypertension in Dialysis Patients—Pathogenesis and Treatment) and Prof. Jacek Manitius (Atrial Fibrillation in Dialysis Patients—Pathogenesis and Treatment). The Progress in Nephrology and Transplantation Conference was yet another international event prepared by the Krakow Centre of Nephrology, which has been successfully managed by Prof. Wladyslaw Sulowicz for nearly 25 years. Since the conference was attended by numerous domestic and foreign leaders in the field of nephrology, its professional and organizational level was extremely high; it is fitting that the 50th anniversary of the first haemodialysis took place in the former capital city of Poland—Krakow [5].

Acute kidney injury (AKI) is a frequent and serious complication in patients with cardiovascular disease. The aim of the study was to evaluate the risk of death in patients with AKI complicating severe cardiovascular diseases.A retrospective analysis of 246 patients surveys (157 men and 89 women aged 67.9 ± 14.8 years) with AKI in the course of severe cardiovascular diseases, hospitalized in intensive care units and words of nephrological profile in years 2000-2011 were performed.The majority of patients (95.9%) with AKI required hemodialysis treatment. The mortality rate in the study group was high and amounted to 69.5% and the recovery of renal function was observed in 39 patients (27.3%). Kidney disease before the onset of AKI was observed in 116 patients (47.2%). Patients with arterial hypertension have more frequently oligoanuria (p = 0.001), needs more hemodialysis sessions (p = 0.029) and stay longer in hospital (p = 0.012). In multivariate analysis, the occurrence of death depend on such factors as: the lack of recovery of renal function, bleeding from gastrointestinal tract, urinary tract infections, and other infectious and noninfectious complications.No recovery of renal function and comorbidity while AKI in the course of severe cardiovascular diseases increase the risk of death.

Patients with cardiovascular diseases are a group of increased risk of acute kidney injury (AKI). Mortality in this group of patients with AKI, especially treated in intensive care units, is very high. The aim of this study was to evaluate the clinical characteristic of patients with AKI complicated severe cardiovascular diseases.Retrospective evaluation of 246 questionnaire of patients with AKI in the course of severe cardiovascular diseases treated in the wards of nephrological profile from the malopolska and podkarpackie voivodships in the years 2000-2011 was performed.The group of patients consisted of 157 men and 89 women, with mean age 67.9 ± 14.8 years. The most common cause of AKI were: acute decompensated heart failure--24 (9.8%), chronic decompensated heart failure--94 (38.2%), cardiac arrest--29 (11.8%), myocardial infarction--48 (19.5%), CABG--12 (4.9%), cardiac valve implantation--14 (5.7), heart transplantation--4 (1.6%) and aortic aneurysm--21 (8.5%). Age distribution of patients with AKI revealed that most numerous group had 71-80 years. The most of patients (95.9%) with AKI were treated with hemodialysis. The mortality rate in the study group was very high (69.5%). Recovery of renal function was observed in 39 (27.3%) of patients. Signs of kidney disease before AKI was noted in 116 (47.2%) of patients.Patients with severe cardiovascular complications and AKI had high mortality rate instead of performed hemodialysis treatment.

With the development of kidney transplantation procedure the number of patients returning to dialysis after losing their graft function is gradually increasing. Early return to dialysis after an unsuccessful kidney transplantation is associated with a worse prognosis. Patients with end stage transplanted kidney failure may be qualified again for the treatment of both peritoneal dialysis or hemodialysis. They represent an increased risk of complications as compared to patients without a history of previous kidney transplantation because they usually have high commorbidity, receive immunosuppressive therapy and during re-qualification to dialysis usually have no efficient vascular access or peritoneal catheter implanted. Graft loss in the early stages after procedure, because of fulminant rejection, vascular thrombosis or lack of primary organ function is associated with immunosuppression withdrawal while leaving a failing kidney is an indication to maintain it in a reduced form. The indication for removal of an inefficient transplant after more than 12 months are: symptoms of its intolerance manifested by acute rejection, pain in the area of the graft, fever, severe anemia, increase of blood pressure and inflammatory markers. Removal of the graft may be associated with a temporary increase in immunization of the patient. Patients meeting the clinical conditions for transplantation should be considered for another kidney transplant as preemptive transplantation or as soon as possible after dialysis start. Although kidney retransplantation results are slightly worse when compared with the first transplant, it still has an advantage over dialysis.

The staging system of chronic kidney disease (CKD) classification plays an important role in patients stratification according to disease activity. The aim of the study was to evaluate the frequency of appearance of consecutive stages of chronic kidney disease based on simplified MDRD formula in patients with diagnosed CKD. Additionally, relationship between eGFR values and selected biochemical parameters and comorbidities were analyzed.The study was performed retrospectively in the group of 1176 patients (636 males and 540 females) aged between 17-98 years (mean 64.7) with creatinine level120 μmol/l and/or creatinine clearance90 ml/min/1.73 m2.The highest percentage of patients were designated to the 3rd CKD stage. There were positive correlations between eGFR and Hb, Ht, Fe, LDL-Ch, AspAT, HbA1c and negative correlations between eGFR and age, mean and systolic blood pressure, as well as with P, K, iPTH, and uric acid concentration. Patients with cardiovascular diseases had significaintly lower eGFR values as compare with patients without such complications, respectively: atrial fibrillation, arterial hypertension, chronic heart failure, ischaemic heart disease (p0.01), and myocardial infarction (p0.04).The highest percentage of patients with diagnosed CKD belong to the 3rd stage of disease. Patients with cardiovascular complications have significantly lower eGFR as compared with those without such disturbances.

Merkel cell carcinoma (MCC) is a rare, neuroendocrine tumour of the skin characterized by a very aggressive course. Firm, red-to-purple, typically non tender papules or nodules is a common of it's clinical manifestation. This carcinoma is more common among white Caucasians males in advanced age. The important risk factors for MCC are immunodeficiency or immunosuppression in patients after organ transplantation. MCC observed in organ recipients is associated with especially rapid progression as compared with general population and tendency to metastasis. Surgical excision of primary tumour with adequate margins and sentinel lymph node dissection with adjuvant radiotherapy improves regional control of disease and patients survival. Chemotherapy is usually used as a palliative treatment for advanced forms of the disease.

Background Patients who are receiving immunosuppressive treatment after kidney transplantation are at greater risk of developing new-onset diabetes after transplantation (NODAT). New biochemical markers that may contribute to a better assessment of the prognosis of renal failure for patients diagnosed with diabetes mellitus (DM) are needed. The aim of this study was to assess selected proinflammatory markers in patients after kidney transplantation depending on the prevalence of DM and to evaluate the predictive value of these cytokines. Methods A total of 82 patients were divided into 3 groups after kidney transplantation and were included in the analysis: group I, no DM; group II, DM diagnosed before transplantation; and group III, NODAT. Selected marker levels (platelet-derived growth factor, transforming growth factor β1, tumor necrosis factor receptor II [TNF-RII], and high-sensitivity interleukin-6 [IL-6 HS]) were assessed by using enzyme-linked immunosorbent assays. For summary endpoint, a return to dialysis treatment and/or death of the patient was adopted. Results Patients with NODAT were characterized by higher levels of IL-6 HS and body mass index. There were no statistically significant differences in the levels of other assessed markers among the 3 analyzed groups. The summary endpoint was observed in 16 cases (19.5%). Patients with summary endpoint during the observation time at baseline had higher levels of TNF-RII (7180 vs 4632 pg/mL; P = .0002) and IL-6 HS (4.58 vs 2.72 pg/mL; P = .033). Conclusions Levels of inflammatory markers in patients after kidney transplantation did not differ between groups with and without DM. In the study population, DM was not a significant risk factor for graft loss or death. Patients who experienced these complications at baseline were characterized by higher values of TNF-RII and IL-6 HS.

Aim: This study was carried out to evaluate the pharmacokinetic profile of α-dihydroergocryptine (CAS 14271-05-7, DHEC, Almirid®) in plasma and urine in patients with moderately to severely impaired renal function (creatinine clearance < 30 ml · min−1 · 1.73 m−2), following administration of single oral doses. Methods: This was an open, nonrandomised trial. Seven patients with chronic renal disease and six healthy subjects received a single dose of 20 mg DHEC. Blood and urine samples were taken at specified intervals up to 72 h after dosing. Concentrations of unchanged DHEC were determined by radio-immunoassay (RIA) and concentrations of unchanged DHEC plus pooled metabolites by enzyme-immunoassay (EIA), respectively. Results: In patients with impaired renal function, the mean Cmax and AUC(0–ȡ) values for unchanged DHEC were 2.1 (95 % confidence interval CI: 0.99 to 4.42) and 1.85 (95 % CI: 0.72 to 4.77) times larger than in controls. The 24-h urinary excretion was only 0.3 (95 % CI: 0.12 to 0.71) times that in healthy subjects. Similar findings were recorded for total DHEC plus metabolites. Conclusions: As treatment with DHEC is in general uptitrated starting with doses as low as 5 mg DHEC, which are then increased while accounting for individual effects both in terms of efficacy and tolerability, the observed range of effects of impaired renal function on DHEC’s pharmacokinetics does not suggest the need to revise this policy, although lower end-doses are likely to be achieved.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The transdermal dopamine agonist rotigotine has been shown to be an efficacious and well tolerated treatment for Parkinson's disease and restless legs syndrome in clinical trials. • The prevalence of Parkinson's disease and restless legs syndrome increases with age. • Renal function deteriorates with age and can influence drug treatment. • Many patients with end-stage renal disease experience restless legs syndrome. WHAT THIS STUDY ADDS • The pharmacokinetic profiles of the active substance, unconjugated rotigotine, were similar in healthy subjects and subjects with renal impairment. • The results suggest that no dose adjustments are required for transdermal rotigotine in subjects with different stages of chronic renal insufficiency including patients on haemodialysis. AIM To evaluate the influence of different stages of chronic renal insufficiency on the pharmacokinetics and safety/tolerability of the transdermally applied dopamine agonist rotigotine in an open label group comparison including 32 subjects (healthy, mild, moderate or severe impairment of renal function and patients with end-stage renal insufficiency requiring haemodialysis). METHODS All subjects received a single transdermal 10 cm2 patch (24 h patch-on period) containing 4.5 mg rotigotine (nominal drug release 2 mg 24 h−1). Main evaluations included relative bioavailability and renal elimination of rotigotine and its metabolites. RESULTS Point estimates for the ratios between the groups with moderate to severe renal impairment and healthy subjects for the pharmacokinetic parameters AUC(0,tlast) and Cmax for the active substance unconjugated rotigotine were near 1:0.88 for AUC and 0.93 for Cmax for moderate renal impairment, 1.14 and 1.18 for severe renal impairment and 1.05 and 1.25 for end-stage renal insufficiency requiring haemodialysis. There was no correlation of these parameters with creatinine clearance. The amount of unconjugated rotigotine excreted into urine and renal clearance decreased with increasing severity of renal insufficiency but had no observable effect on total clearance as the amounts excreted were below 1% of the administered dose. Occurrence of adverse events did not increase with the degree of renal insufficiency. CONCLUSIONS The pharmacokinetic profiles of unconjugated rotigotine were similar in healthy subjects and subjects with impaired renal function indicating that no dose adjustments are required for transdermal rotigotine in patients with different stages of chronic renal insufficiency including patients on haemodialysis.

Summary Background Carpal tunnel syndrome (CTS) is the most common complication of dialysis-related amyloidosis (DRA) developing in patients on long-term dialysis therapy. The aim of this study was to evaluate the incidence of CTS and identify factors influencing the development of CTS in patients on maintenance hemodialysis, as well as results of its surgical treatment. Material/Methods The study included 386 patients, among whom CTS was diagnosed in 40 patients (10.4%) on the basis of signs and physical symptoms, as well as by nerve conduction. The group of patients with CTS and the group of patients without CTS were compared according to age (mean 54.50 vs. 56.48 years) and duration of dialysis treatment. Initial analysis of CTS incidence by sex, presence of anti-HCV antibodies, and location of arterio-venous fistula (AV fistula) was undertaken. Results Duration of dialysis treatment was the statistically significant risk factor for the development of CTS (16.05 vs. 4.51 years; p