Pharmacokinetics, Safety, and Tolerability of Glepaglutide, a Long-Acting GLP-2 Analog, in Subjects with Renal Impairment.

BACKGROUND: Glepaglutide is a novel, ready-to-use, long-acting, glucagon-like peptide-2 (GLP-2) analog intended for the treatment of patients with short bowel syndrome (SBS). This study investigated the impact of renal function on the pharmacokinetics and safety of glepaglutide. METHODS: In this 3-site, non-randomized, open-label study, 16 subjects were enrolled: 4 with severe renal impairment (eGFR 15 to < 30 mL/min/1.73 m2), 4 with end stage renal disease (ESRD) not on dialysis (eGFR < 15 mL/min/1.73 m2), and 8 matching controls with normal renal function (eGFR ≥ 90 mL/min/1.73 m2). Blood samples were collected over a 14-day period following a single subcutaneous (SC) dose of glepaglutide 10 mg. Safety and tolerability were assessed throughout the study. The primary pharmacokinetic parameters were area under the curve between dosing and 168 h (AUC0-168 h) and the maximum plasma concentration (Cmax). RESULTS: There was no clinically relevant difference between subjects with severe renal impairment/ESRD and normal renal function with respect to total exposure (AUC0-168 h) and peak plasma concentrations (Cmax) of glepaglutide following a single SC dose. A single SC dose of glepaglutide 10 mg appeared safe and well tolerated in subjects with normal renal function and subjects with severe renal impairment or ESRD. No serious adverse events were reported, and no safety issues were identified. CONCLUSIONS: No difference in glepaglutide pharmacokinetics was seen between renal impaired and normal subjects. Based on this trial, dose adjustment appears not to be warranted in SBS patients with renal impairment. TRIAL REGISTRATION: The trial is registered at http://www. CLINICALTRIALS: gov (NCT04178447) and has the EudraCT number: 2019-001466-15.

Efficacy and Cardiovascular Safety of Roxadustat in Dialysis-Dependent Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies.

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.

Roxadustat for the Maintenance Treatment of Anemia in Patients with End-Stage Kidney Disease on Stable Dialysis: A European Phase 3, Randomized, Open-Label, Active-Controlled Study (PYRENEES).

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.

Roxadustat for the treatment of anemia in chronic kidney disease patients not on dialysis: a Phase 3, randomized, double-blind, placebo-controlled study (ALPS).

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 < 0.001]. Superiority of roxadustat was demonstrated for low-density lipoprotein cholesterol change from BL, and time to first use of rescue medication (both P < 0.001). The incidences of treatment-emergent adverse events were comparable between groups (roxadustat: 87.7%, placebo: 86.7%). CONCLUSIONS: Roxadustat demonstrated superior efficacy versus placebo in terms of both Hb response rate and change in Hb from BL. The safety profiles of roxadustat and placebo were comparable.

Comparison of Kidney Transplant Function, Lipid Metabolism Disorders, and Glucose and Hemoglobin Concentration in Transplant Patients Treated With Proliferation Signal Inhibitor (Everolimus) or Calcineurin Inhibitor (Tacrolimus).

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.

Post-transplant Lymphoproliferative Disorder in a Patient After Kidney Transplant, 5-Year Follow-up: A Case Report.

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.

Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease.

BACKGROUND: Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. AIMS: We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. METHODS: Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima­media thickness and atherosclerotic plaques were assessed by ultrasonography. RESULTS: In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima­media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C­reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). CONCLUSIONS: In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.

Proteoglycan/glycosaminoglycan and collagen content in the arterial wall of patients with end-stage renal disease: new indicators of vascular disease.

INTRODUCTION: The prevalence of cardiovascular (CV) comorbidity in patients with chronic kidney disease (CKD) is high, particularly in end­stage 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 (PAI­1), stromal cell­derived factor 1α (SDF­1α), calcium (Ca), phosphate (Pi), intact parathormone, interleukin 6, high­sensitivity C­reactive protein (hs­CRP), ferric reducing ability of plasma, 2,2­diphenyl­1­picrylhydrazyl scavenging, ferric reducing ability of ascorbate in plasma, fetuin­A, fibroblast growth factor 23, osteopontin, osteoprotegerin, osteocalcin, transforming growth factor ß (TGF­ß), 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, hs­CRP, fibrinogen, SDF­1α, PAI­1, and sTM. However, PAI­1 was the only significant predictor of grade 3 alcian blue staining in a multiple logistic regression model adjusted for hemodialysis, Ca× Pi product, and hs­CRP levels. CONCLUSIONS: Coagulation disorders and endothelial dysfunction are the hallmarks of ESRD. The levels of SDF­1α, PAI­1, sTM, and fibrinogen may be novel predictors of early vascular wall alterations and may serve as CV risk markers.

Endothelial injury is closely related to osteopontin and TNF receptor-mediated inflammation in end-stage renal disease.

BACKGROUND: Endothelial dysfunction, inflammation and active mineralization are key processes involved in cardiovascular burden in end stage renal disease (ESRD). Serum (soluble) thrombomodulin (sTM) is an established marker of endothelial injury. PATIENTS: 80 patients in ESRD were recruited consecutively. Baseline distribution of sex, age, main comorbidities and Framingham score was similar. A biochemical panel including sTM, intact PTH (iPTH), interleukin-6 (IL-6), pentraxin 3 (PTX3), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteonectin (ON), soluble tumor necrosis factor receptor type 2 (TNFR2), transforming growth factor-ß (TGF-ß), hepatocyte growth factor (HGF), vascular endothelial growth factor receptor type 2 (sVEGFR2) and stromal cell-derived factor 1α (SDF1α) was investigated in each patient. Samples obtained while establishing haemodialysis (HD) access were stained for radial artery calcifications (RACs) with Alizarin red and examined histologically. RESULTS: After adjustment for HD status, sTM showed a significant positive correlation with serum creatinine, TNFR2, OPN, HGF, SDF1α, sVEGFR2, Pi, iPTH, FGF-23, OPG, OC and ON. In forward stepwise multiple regression, serum creatinine, TNFR2, and OPN were identified as significant, independent predictors of sTM. Grades 1-3 of RACs correlated with sTM (R = 0.50, p = 0.017), while grade 3 RACs were significantly associated with higher sTM (p = 0.02) than less advanced lesions. CONCLUSION: Among novel renal and cardiovascular biomarkers, OPN and TNFR2 are closely related to sTM. This may link endothelial damage, vascular remodeling and inflammation. Progression of RAC parallels a presumed compensatory rise in sTM, reflecting endothelial injury. sTM has an intricate role in endothelial function and potential clinical and prognostic applications.

The clinical implication of monoclonal gammopathies: monoclonal gammopathy of undetermined significance and of renal significance.

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.

Microbiology and Drug Resistance of Pathogens in Patients Hospitalized at the Nephrology Department in the South of Poland.

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 ß-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 ß-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 (79.7­89.5%). Low sensitivity was found in relation to fluoroquinolones (60.3­70.4%). 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.

Fatty acids profile in patients after heart or renal transplantation who developed metabolic complications.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

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

We studied the correlations between circulating osteoprotegerin (OPG) level and radial artery calcification (RAC) assessed histologically and carotid artery intima-media thickness (CCA-IMT). Moreover, we studied the relationship between OPG levels and all-cause and cardiovascular (CV) mortality during a 5-year observation period. The study comprised 59 CKD patients (36 hemodialyzed (HD), 23 predialysis). The biochemical parameters included: creatinine, calcium, phosphate, intact parathormone, C-reactive protein, interleukin-6, tumor necrosis factor receptor II (TNFRII), transforming growth factor-ß, 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.

Asymmetric dimethylarginine as a useful risk marker of radial artery calcification in patients with advanced kidney disease.

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 (CCA­IMT). 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 cell­derived factor 1α (SDF1α), thrombomodulin, soluble tumor necrosis factor receptor II (sTNFRII), and matrix metalloproteinase 2 (MMP­2) were determined. Radial artery fragments were stained for calcifications using alizarin red. The CCA­IMT 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, MMP­2, thrombomodulin, and they had more atherosclerotic plaques in the carotid artery. In multiple regression, log­transformed (log)sTNFRII, MMP­2, 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.

Beneficial effect of kidney transplantation from a deceased donor on severe chronic refractory intradialytic hypotension - a case report.

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.

Comparison of the incidence of skin cancers in patients on dialysis and after kidney transplantation.

INTRODUCTION: Kidney transplant (KTx) patients on immunosuppressive therapy are predisposed to the development of infections and cancers. AIM: To compare the incidence and type of malignant skin lesions in kidney transplant patients and the dialyzed population based on the initiated dermatologic screening. MATERIAL AND METHODS: The study included 598 patients: 486 kidney transplant recipients and 112 patients on maintenance dialysis. All the patients underwent dermatological examination. Only histologically confirmed cancers were included in this study. Age, gender and immunosuppressive therapy administration were also considered. Patients were followed up by a dermatologist for a period of 5 years. RESULTS: Fifty-eight skin cancers; 39 basal cell carcinomas (BCC), 13 squamous cell carcinomas (SCC), 1 Bowen disease, 2 Kaposi sarcoma, 1 malignant melanoma, 1 Merkel cell carcinoma, and 1 fibrosarcoma protuberans were diagnosed in 30 (6.2%) kidney transplant patients, and 8 lesions (7 BCC and 1 SCC) were found in 4 (3.6%) patients on dialysis. CONCLUSIONS: The initiated dermatologic screening program indicates that the risk of skin cancer incidence in post kidney transplant patients receiving immunosuppressive therapy was significantly higher than in patients on dialysis.