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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., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

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.

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., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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-β (TGF-β), 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

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., (© 2018 Mikołaj Michno et al.)

Competing Interests: The authors declare no conflict of interest.

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: 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., Competing Interests: The authors declare no conflict of interest.

INTRODUCTION    Pentraxin3 (PTX3) play an important role in the inflammatory response, taking part in recognizing pathogens and damaged tissues. OBJECTIVES    The aim of the study was to assess the relationship between PTX3 levels and all-cause and cardiovascular (CV) mortality in chronic kidney disease (CKD) patients during five-year observation period.  PATIENTS AND METHODS    The study comprised 78 patients (51 hemodialyzed, 27 predialysis). The examined parameters included PTX3, calcium, phosphate, iPTH, interleukin-6 (IL-6), fibroblast growth factor 23 (FGF-23), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), osteoprotegerin (OPG), osteocalcin, tumor necrosis factor receptor II (TNF-R II), transforming growth factor-β (TGF-β), hepatocyte growth factor (HGF), stromal cell-derived factor α (SDF1α), and thrombomodulin (TM). In a subgroup of 45 patients, fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications. In 51 patients, ultrasonography was performed to assess intima-media thickness (CCA-IMT).  RESULTS    Median serum concentration of PTX3 was 1.43 (0.74-2.50) ng/ml. Higher concentrations of fibrinogen, CRP, IL-6, TNF-R II, TGFβ1, HGF, OPN, OPG, FGF-23, TM, SDF1α, lower albumin and uric acid levels were observed in patients with PTX3 above the median. During follow-up, 27 patients (35%) died, including 25 due to CV causes. In contrast to CRP, baseline PTX3 predicted CV mortality independently of classical CV risk factors. Also, PTX3 concentrations significantly predicted mortality after adjustment for age, baseline dialysis status, serum OPG and CRP, radial artery calcifications, and CCA-IMT. CONCLUSIONS    We postulate that PTX3 might be an early marker of CV mortality in patients with advanced CKD yet before the increase of specific marker for systemic inflammation like hsCRP.

Purpose Disrupted bone metabolism in patients with chronic kidney disease (CKD) is associated with elevated concentrations of biochemical bone markers. Recently, animal studies show the role of osteocalcin in energy metabolism, which is partially confirmed in humans. The aim of our study was to evaluate the relationships between serum concentrations of bone markers and indices of energy metabolism in CKD patients on maintenance hemodialysis; in particular, the relationship between various forms of osteocalcin and adiponectin. Patients and methods The cross-sectional study included 155 hemodialyzed stage 5 CKD patients. Serum concentrations of glucose, insulin, adiponectin, bone alkaline phosphatase (bALP), tartrate resistant acid phosphatase (TRAP), carboxylated (cOC), undercarboxylated (ucOC), and intact osteocalcin (OC) were determined. Results In total cohort, bALP, TRAP, cOC, and ucOC negatively correlated with BMI. All analyzed bone markers positively correlated with adiponectin in total cohort and in men. In multiple linear regression analysis including all patients, log(cOC) and log(intact OC) were the only bone markers that predicted log(adiponectin) (beta = 0.22; p = 0.016 and beta = 0.26; p = 0.010) independently of sex, dialysis vintage, CRP, insulin, iPTH concentrations, BMI, and age. Conclusions Our data confirm the positive association between cOC, intact OC, and adiponectin concentrations in CKD patients on maintenance hemodialysis.

Background: The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD)., Methods: The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red., Results: Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)]., Conclusions: In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Objectives: Our aim was to determine whether vascular deposition of advanced glycation end-products (AGEs) is associated with arterial calcification and cardiovascular mortality in chronic kidney disease (CKD) patients and to assess the relationships between vascular content of AGEs and selected clinical and biochemical parameters., Materials and Methods: The study comprised 54 CKD patients (33 hemodialyzed, 21 predialyzed). Examined parameters included BMI, incidence of diabetes, plasma fasting glucose, AGEs, soluble receptor for AGEs and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging, serum C-reactive protein (hsCRP), plasminogen activator inhibitor-1 (PAI-1), and fetuin-A. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using alizarin red. AGEs deposits were identified immunohistochemically and their relative content was quantified., Results: Vascular content of AGEs was positively correlated with BMI, hsCRP, fetuin-A, PAI-1, and DPPH scavenging in simple regression; only fetuin-A was an independent predictor in multiple regression. There was a significant positive trend in the intensity of AGEs immunostaining among patients with grades 1, 2, and 3 calcifications. AGEs immunostaining intensity predicted 3-year cardiovascular mortality irrespective of patient's age., Conclusions: The present study demonstrates an involvement of AGEs in the development of medial arterial calcification and the impact of arterial AGE deposition on cardiovascular mortality in CKD patients.

Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20-24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death.

Background and Objectives: Peginesatide is a synthetic, PEGylated, investigational, peptide-based erythropoiesis-stimulating agent. We report the first assessment of its efficacy and safety in correcting renal anemia in a population of 139 nondialysis chronic kidney disease patients., Design, Setting, Participants, & Measurements: Chronic kidney disease patients who were not on dialysis and not receiving treatment with erythropoiesis-stimulating agents in the 12 weeks before study drug administration were sequentially assigned to one of 10 cohorts; cohorts differed in starting peginesatide dose (different body weight-based or absolute doses), route of administration (intravenous or subcutaneous), and frequency of administration (every 4 or 2 weeks)., Results: Across all cohorts, 96% of patients achieved a hemoglobin response. A dose-response relationship was evident for hemoglobin increase. Comparable subcutaneous and intravenous peginesatide doses produced similar hemoglobin responses. Rapid rates of hemoglobin rise and hemoglobin excursions >13 g/dl tended to occur more frequently with every-2-weeks dosing than they did with every-4-weeks dosing. The range of final median doses in the every-4-weeks dosing groups was 0.019 to 0.043 mg/kg. Across all cohorts, 20% of patients reported serious adverse events (one patient had a possibly drug-related serious event) and 81% reported adverse events (11.5% reported possibly drug-related events); these events were consistent with those routinely observed in this patient population., Conclusions: This study suggests that peginesatide administered every 4 weeks can increase and maintain hemoglobin in nondialysis chronic kidney disease patients. Additional long-term data in larger groups of patients are required to further elucidate the efficacy and safety of this peptide-based erythropoiesis-stimulating agent.

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<0.0001). Among patients treated for a long period on hemodialysis (20-30 years), 100% required surgical release procedures, while 66.66% of those treated for 15-19 years, 42.1% of those treated for 10-14 years, and 1.6% of those treated for less than 10 years. CTS was diagnosed more often in anti-HCV-positive patients as compared with anti-HCV-negative patients (47.5 vs. 6.9%; p<0.0001). No significant differences were found when comparing CTS incidence by sex or between the development of CTS requiring surgical release intervention and location of the AV fistula., Conclusions: Surgical release procedure of the carpal tunnel gave good treatment results in patients with CTS.

The most characteristic finding in non-typhoid salmonella (NTS) infection is acute food related outbreaks of gastroenteritis, which is usually benign and self-limiting. However, more serious extraintestinal findings, such as bacteraemia and focal infections localized to any organ may appear. The objective of this paper is to describe the most important characteristic of the extraintestinal infections due to NTS serotypes observed in University Hospital, in Cracow between January 2000 and December 2006. To do so, we reviewed the clinical presentations, risk groups, complications and outcomes of in-patients, in which extraintestinal non-typhoid Salmonella serotypes were isolated, applying a clinomicrobiological protocol. Out of 30 patients with either bacteraemias (n = 22) or focal salmonella infections (n = 8), 12 had malignancies, 17 had immune dysfunction state, 9 had gastrointestinal disorders and 8 had chronic heart, pulmonary or kidney disease. Four of these patients (13%) who had hematological malignancies (2), renal transplantation (1) and pulmonary disease (1) died. Regarding the clinical picture, primary bacteraemia and focal infections occurred with similar frequency (33.3% and 26.7%, respectively); the remaining were bacteraemias secondary to gastroenteritis. The incidence rate (mean 0.30/1000 hospital admission/year) increased steadily from 0.19/1000 to 0.32/1000 hospital admission during the study period. From 30 Salmonella isolates from extraintestinal samples collected, only four isolates were resistant to ampicillin, ciprofloxacin or trimethoprim-sulfamethoxazole. This finding indicate that multidrug resistance does not represent a serious problem among NTS serotypes collected from the our medical center as monitored over a period of 7 years. Given this presentation, clinicians need to have a high index of suspicion and to consider preemptive therapy, especially in elderly patients who are likely to develop severe immunosuppression following interventions.

Previous clinical data suggested that with a tacrolimus-based regimen adjunctive immunosuppressives may be withdrawn after an initial treatment period. This study investigated the early discontinuation of mycophenolate mofetil (MMF) from a standard triple regimen. Patients were randomized either to receive a continued tacrolimus/MMF/steroids triple regimen (control group) or to reduce and then stop the MMF dose (MMF stop group). Both groups received identical daily tacrolimus and corticosteroid doses. The initial MMF dose was 1 g/day in both arms, but in the MMF stop group the dose was reduced to 0.5 g/day from week 7 to week 12 and then stopped. The intent-to-treat population consisted of 74 (control) and 78 (MMF stop) patients. MMF was tapered off as planned in 82.9% of the patients in the MMF stop arm. The 6-month incidence of biopsy-proven acute rejection was similar in both arms (21.6% control, 16.7% MMF stop). Graft loss occurred in 5.4% (control) and 3.8% (MMF stop) of the patients. MMF could be safely discontinued from a tacrolimus-based triple therapy early after transplantation without any rebound in efficacy during the 6-month follow-up period. (Name of registry: ClinicalStudyResults.org, number: FG-02-CEE-01, date: 9 June 2006).

Glomerulonephritis is one of the diseases leading to chronic renal failure and need of renal replacement therapy. Changes in extraglomerular compartments, especially in the interstitium, are thought to play a major role in progression. However, the exact relationships between renal interstitium, tubules and vessels and their prognostic impact are less well understood. The material consisted of 111 biopsies with primary glomerulonephritis. Normal renal tissue from surgically removed kidneys served as controls. Relative interstitial volume (RIV), its variability, volume of interstitial infiltrate, cross-sectional tubular area were measured with the point-counting method. A number of vascular parameters were also measured. The assessed interstitial and tubular parameters were strongly correlated to creatinine level. The strongest correlation was seen for RIV, also on multiple regression. In patients with renal failure, increased RIV, more pronounced vascular lesions and interstitial infiltrates were seen. Survival analysis showed that interstitial expansion is the most important factor leading to renal failure. Tubulointerstitial and vascular factors are interrelated and linked to renal function. RIV has strongest impact on renal function and survival, even taking into account other factors.

The term glomerulonephritis encompass a heterogeneous group of diseases; these are a important cause of end stage renal disease. Although several evidence exist, that the main prognostic factors are extraglomerular lesions, no quantitative assessment is usually done. In nephropathological practice a semiquantitative approach is preferred. However, most of work on extraglomerular lesions significance was done with quantitative methods. The aim of the study was to compare the effects of quantitative and semiquantitative assessment of extraglomerular lesions in glomerulonephritis. The material consisted of 120 renal biopsies. On inspection, percentage of sclerosed glomeruli, degree of interstitial fibrosis, degree of interstitial infiltration, degree of tubular atrophy were and degree of mesangial matrix expansion assessed. For quantitative measurements AnalySIS 3.0 pro image analysis system was used. Relative interstitial volume, volume of interstitial infiltrate, with their variability--ross sectional areas of proximal and distal tubules were assessed by point counting method. Relative interstitial volume was significantly correlated to percentage of sclerosed glomeruli (R = 0.33 p < 0.001), degree of tubular atrophy (gamma = 0.57 p < 0.00001), degree interstitial fibrosis (gamma = 0.31 p < 0.0002) and mesangial matrix expansion (gamma = 0.24 p < 0.001). Semiquantitative and quantitative assessment of interstitial infiltrate was significantly correlated as well (gamma = 0.81 p < 0.001). Semiquantitatively assessed degree of tubular atrophy showed significant relation to total proximal tubular area (gamma = -0.30 p = 0,004). Percentage of sclerosed glomeruli was significantly correlated to creatinine level (R = 0.24 p = 0.03), but not to urea level (R = 0.09, NS). Semiquantitatively assessed degree of interstitial fibrosis showed only marginal correlation to creatinine level (gamma = 0.18 NS), however degree of interstitial infiltration was significantly correlated to creatinine (gamma = 0.34 p = 0.002) and urea level (gamma = 0.22 p = 0.06). Degree of tubular atrophy was significantly correlated to creatinine (gamma = 0.43 p < 0.001) and urea level (gamma = 0.28 p = 0.015). Relative interstitial volume was the very most important correlate of creatinine (R = 0.47 p < 0.0001) and urea level (R = 0.30 p < 0.01). In conclusion, it was confirmed, that the strongest correlate of renal function is relative interstitial volume. Some, but not all of semiquantitative parameters are also significantly correlated to kidney function.

Background: Accelerated atherosclerosis and vascular calcifications increase cardiovascular morbidity and mortality in patients on dialysis. Common carotid artery (CCA) intima-media thickness (IMT) is considered useful for imaging atherosclerosis non-invasively. Since chronic inflammation may accelerate atherosclerosis in end-stage renal disease patients, the aim of this 1 year study was to assess changes in CCA-IMT in stable peritoneal dialysis (PD) patients, and to search for possible associations between these changes and selected cytokines, acute phase proteins and other risk factors of atherosclerosis., Methods: Of the original cohort of 61 stable patients on PD-28 female, 33 male; mean age 50.4+/-13.6 years; dialyse for a median of 17.5 months at inclusion (range 1-96 months)-47 patients survived the 1 year period on PD. CCA-IMT was assessed at baseline and after 12 months. Pro-inflammatory cytokines (IL-6, TNFalpha), acute phase proteins (CRP, fibrinogen), calcium-phosphate balance and lipid profile were assessed at baseline and after 6 and 12 months. Anthropometric parameters (age, weight, BMI, waist-to-hip ratio) were measured at baseline., Results: The mean CCA-IMT at baseline, 0.66+/- 0.19 mm, increased by a mean of 0.098+/-0.17 to 0.76+/-0.21 mm (P<0.001) in 1 year. In 14 patients (29.8%) at least one plaque was found in the CCAs examined. At the end of follow-up: 28 patients (59.6%) had increases in CCA-IMT (from 0.63+/-0.2 to 0.83+/- 0.21 mm; P = 0.03), and 19 (40.4%) remained stable or even showed slight, but non-significant, decreases of CCA-IMT (from 0.72+/-0.17 to 0.66+/-0.17 mm, P = NS). The 'progressors' had significantly higher initial BMI (P<0.05), and mean concentrations of calcium (P = 0.005), IL-6 (P = 0.05), TNFalpha (P = 0.05), CRP (P = 0.005) and lower HDL-cholesterol than 'non-progressors'. In univariate analysis, DeltaCCA-IMT correlated positively with age (R = 0.32, P = 0.03), BMI (R = 0.29, P = 0.05) and mean concentrations of CRP (R = 0.37, P = 0.01), TNFalpha (0.52, P = 0.0002), but inversely with HDL-cholesterol (R = -0.37, P = 0.01). In multiple regression analysis, however, only age appeared to be independently associated with increase in CCA-IMT (beta = 0.37, P<0.01; R(2) for the model 0.14)., Conclusions: Our results suggest a possible role of non-specific inflammation in the progression of atherosclerosis in patients treated with PD, in addition to age.

Background: Continuous ambulatory peritoneal dialysis (CAPD) is an alternative to the hemodialysis mode of terminal renal failure treatment. Nutritional status impairment is common among patients with end-stage renal disease, and its laboratory surrogates predict increased morbidity and mortality risk in patients on chronic haemodialysis or peritoneal dialyses. The aetiology of malnutrition is multifactorial and delayed gastric emptying is also considered to be a significant factor. The aim of this study was to estimate the direct influence of indwelled dialysate in the peritoneal cavity on gastric emptying in patients treated with CAPD., Material and Methods: the study group included 20 patients (9 males, 11 females) aged 50,1 +/- 11 years (range: 39-75 years) with chronic renal failure treated with CAPD for 18.4 +/- 14.7 months. All patients were non-diabetic and had no other than chronic uraemia co-morbidity known to influence autonomic nervous system function and gastric motility. The control group included 15 healthy volunteers matched by age, sex and body weight. Dialysis adequacy parameters were calculated based on 24-hour urine and dialysate collections. Gastric emptying was estimated with dynamic abdominal scintigraphy. We compared the results of gastric emptying tests performed in dialysed patients with and without dialysate liquid in the peritoneal cavity and related the values to those of the control subjects., Results: In the study group, weekly values of dialysis parameters were within the ranges considered satisfactory in terms of uraemia control. All parameters of gastric emptying were significantly delayed and prolonged in terminal renal failure patients, but the results have shown no significant differences between those with and without indwelling dialysate., Conclusions: Based on the results we conclude that gastric emptying in subjects with chronic renal failure treated with CAPD is markedly delayed compared to healthy subjects. There was no significant effect of indwelling dialysate in the peritoneal cavity on gastric emptying rates found, based on the observation that its removal was not associated with any noticeable improvement of gastric emptying. The data strongly contraindicate the theory of peritoneal dialysate volume being the cause of this reversible disorder and indicate that the role of other possible factors leading to the development of gastropathy in those patients should be investigated.

Background: Low molecular weight proteins (LMWP) are considered uremic toxins. There is controversy whether in peritoneal dialysis (PD) the elimination of these toxins is influenced mainly by dialysis or by residual renal function (RRF)., Material/methods: The aim of our study was to evaluate the relationship between serum levels of selected LMWPs, dialysis adequacy, and RRF in PD patients. 27 stable subjects were studied, mean age 50+/-11, dialyzed for a median period of 10 months. Serum activity of acid RNA-se and alkaline RNA-se was measured by spectrophotometry, and serum alpha1-microglobulin ((alpha) 1M) concentration by ELISA. Kt/V and weekly creatinine clearance (wClCr) were assessed as adequacy indices (both as the sum of renal and dialysis components) and RRF as the mean of residual urea and creatinine clearances., Results: Significant inverse correlations were found between RRF and (alpha) 1M level, as well as alkaline RNA-se activity (p<0.0001). A similar relationship was found for residual Kt/V (p<0.0001 for (alpha) 1M and alkaline RNA-se). There was no significant correlation between acid RNA-se activity and any tested parameter of adequacy. When the cutoff points of wClCr = 60 L/week/m2, total Kt/V = 2.0, or RRF=2.0 ml/min were used, we found (alpha)1M level and alkaline RNA-se activity to be significantly lower in patients with higher values of the, Conclusions: RRF plays an important role in elimination of LMWP in PD. The activity of alkaline RNA-se and acid RNA-se behaves differently in these patients.

Background: Rhabdomyolysis is a relatively rare, not always diagnosed cause of acute renal failure (ARF). This fact motivated us to present the results of ARF treatment in the course of this polyetiological clinical syndrome., Material/methods: The analysis was performed on 84 patients (6 F, 78 M) ranging in age from 18 to 82 years (mean 46.5), in whom rhabdomyolysis was diagnosed based on clinical manifestation and laboratory test results (CPK, GTP, GOT, LDH)., Results: The most frequent cause of rhabdomyolysis was alcoholic intoxication (41 patients), often accompanied by hypothermia (15 patients) or trauma (30 patients). Isolated trauma was found in 30 patients, epileptic seizure in 5, and physical exercise in 1 case. In 17 patients, besides alcohol consumption, trauma or epileptic seizure, the use of tranquilizers, anticonvulsants, or narcotic drugs was additionally noted. 78 patients developed ARF requiring dialysis therapy; 49 patients recovered, 5 required maintenance dialysis, and 30 died., Conclusions: During the initial phase of ARF in the course of rhabdomyolysis dynamic increases in serum urea and creatinine were observed, as well as a tendency to hyperkalemia. The treatment results and mortality rate in our study group were primarily influenced by the patients' general condition at admission, as well as the extent of organ damage caused by the primary etiological factor. Favorable treatment results were obtained especially in those patients who were hospitalized in a nephrological center, while the worst outcomes were noted in those patients dialyzed in intensive care units, most with multiple trauma.

To investigate further the biologic activity of solutes in the middle-molecular-weight range, we studied the influence of these compounds on the migration of unseparated white blood cells and separated granulocytes and lymphocytes. Middle molecules (MM) inhibit the migration of unseparated leukocytes, but this effect on lymphocytes was seldom observed. With scanning electron microscopy, unseparated leukocytes were shown to adhere to one another, forming cellular clumps. This phenomenon could not be seen when separated cells were used. These results give some insight into the mechanism of inhibition exerted by MM and into the changes, observed in earlier experiments, of cellular composition of skin exudate obtained from untreated patients with uremia.