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.

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.

Clinicopathologic correlations of renal pathology in the adult population of Poland.

BACKGROUND: This is the first report on the epidemiology of biopsy-proven kidney diseases in Poland. METHODS: The Polish Registry of Renal Biopsies has collected information on all (n = 9394) native renal biopsies performed in Poland from 2009 to 2014. Patients' clinical data collected at the time of biopsy, and histopathological diagnoses were used for epidemiological and clinicopathologic analysis. RESULTS: There was a gradual increase in the number of native renal biopsies performed per million people (PMP) per year in Poland in 2009-14, starting from 36 PMP in 2009 to 44 PMP in 2014. A considerable variability between provinces in the mean number of biopsies performed in the period covered was found, ranging from 5 to 77 PMP/year. The most common renal biopsy diagnoses in adults were immunoglobulin A nephropathy (IgAN) (20%), focal segmental glomerulosclerosis (FSGS) (15%) and membranous glomerulonephritis (MGN) (11%), whereas in children, minimal change disease (22%), IgAN (20%) and FSGS (10%) were dominant. Due to insufficient data on the paediatric population, the clinicopathologic analysis was limited to patients ≥18 years of age. At the time of renal biopsy, the majority of adult patients presented nephrotic-range proteinuria (45.2%), followed by urinary abnormalities (38.3%), nephritic syndrome (13.8%) and isolated haematuria (1.7%). Among nephrotic patients, primary glomerulopathies dominated (67.6% in those 18-64 years of age and 62.4% in elderly patients) with leading diagnoses being MGN (17.1%), FSGS (16.2%) and IgAN (13.0%) in the younger cohort and MGN (23.5%), amyloidosis (18.8%) and FSGS (16.8%) in the elderly cohort. Among nephritic patients 18-64 years of age, the majority (55.9%) suffered from primary glomerulopathies, with a predominance of IgAN (31.3%), FSGS (12.7%) and crescentic GN (CGN) (11.1%). Among elderly nephritic patients, primary and secondary glomerulopathies were equally common (41.9% each) and pauci-immune GN (24.7%), CGN (20.4%) and IgAN (14.0%) were predominant. In both adult cohorts, urinary abnormalities were mostly related to primary glomerulopathies (66.8% in younger and 50% in elderly patients) and the leading diagnoses were IgAN (31.4%), FSGS (15.9%), lupus nephritis (10.7%) and FSGS (19.2%), MGN (15.1%) and pauci-immune GN (12.3%), respectively. There were significant differences in clinical characteristics and renal biopsy findings between male and female adult patients. CONCLUSIONS: The registry data focused new light on the epidemiology of kidney diseases in Poland. These data should be used in future follow-up and prospective studies.

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.

Patient after renal transplantation with syncope: Role of echocardiography in upright position.

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.

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.

Carboxylated and intact osteocalcin predict adiponectin concentration in hemodialyzed patients.

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.

[Comparison of the prevalence of chronic kidney disease in patients of the Emergency Department of the Regional Hospital in Kielce based on GFR estimation according abbreviated MDRD formula or CKD-EPI equation].

Introduction: 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 formulas Materials and Methods: The 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. Results: 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. Conclusions: Both formulas have the similar value in the estimation of CKD. The differences concerning mainly G1 and G2 stages.

[The prevalence of chronic kidney disease among patients of the Emergency Department of the Regional Hospital in Kielce].

The prevalence of chronic kidney disease (CKD) in the world is constantly increasing. This is related to the eldering of the societies, growing numbers of patients with diabetes, hypertension, atherosclerosis and obesity. The progress of the disease increases the risk of complications and mortality, especially from cardiovascular causes and leads to end-stage renal disease requiring renal replacement therapy. The analysis involving 1452 patients (762 women and 690 men aged 57.4 years ± 19.8 years) from the Emergency Department in Kielce revealed reduced eGFR below 60 ml/ min/1,73 m2 in 474 (32.6%) of participants and mean values of eGFR was 68.6 ± 22.3 ml/min/1.73 m2. Such high percentage of patients fulfilling criteria of CKD may be due to the fact that to the Emergency Department coming patients with high comorbidity and with increased risk of kidney disease.

[Risk factors of death occurrence in patients with acute kidney injury in the course of severe cardio-vascular complications]. / Czynniki ryzyka zgonu u chorych z ostrym uszkodzeniem nerek w przebiegu ciezkich powiklan sercowo-naczyniowych.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: No recovery of renal function and comorbidity while AKI in the course of severe cardiovascular diseases increase the risk of death.

[Clinical characteristic of patients with acute kidney injury complicated severe cardio-vascular diseases]. / Charakterystyka kliniczna pacjentów z ostrym uszkodzeniem nerek wiklajacym ciezkie schorzenia sercowo-naczyniowe.

INTRODUCTION: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Patients with severe cardiovascular complications and AKI had high mortality rate instead of performed hemodialysis treatment.

[Recovery of renal function and comorbidities in patients with acute kidney injury in the course of severe cardiovascular complications].

Introduction: 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. Material and Methods: 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. Results: 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 (p<0.001 and p = 0.007). Patients staying longer at hospital has more frequent recovery of renal function (p = 0.014). Conclusions: Probability of renal function recovery in patients with AKI in the course of severe cardio-vascular complications is low.

Relationship between fetuin-A, bone turnover and inflammatory markers concentrations in serum of maintenance hemodialyzed patients.

Introduction: Fetuin-A plays an important role in bone turnover and vascular calcification. Aim: The aim of the study was to assess the relationship between serum fetuin-A concentrations, inflammatory and bone turnover markers of patients on maintenance hemodialysis. Materials and Methods: The study was performed in 71 patients (21 women, 40 men) aged 60 ± 12 years on chronic dialysis because of end-stage renal failure for a period of 75 ± 57.2 months. The routine laboratory tests were performed with Modular P analyzer (Roche Diagnostics), serum concentrations of iPTH were measured using Nichols method, hsCRP and IL-6 using nephelometric techniques while fetuin-A, bone-specific alkaline phosphatase (bALP), fully carboxylated osteocalcin (cOC), undercarboxylated osteocalcin (ucOC), and fibroblast growth factor-23 (FGF-23) were measured using commercially available ELISA kits. Results: Concentrations of fetuin-A were significantly positively correlated with albumin (r=0.37, p=0.003) and negatively associated with patients age (r=26, p=0.04), log (iPTH) (r=0.31, p=0.02), log (CRP) (r=0.31, p=0.02), log (IL-6) (r=0.41, p=0.001), log (ucOC) (r=-0.29, p=0.02), and log (FGF-23) (r=0.27, p=0.04). Conclusions: 1. Patients on maintenance hemodialysis suffer from severe disturbances of bone turnover. 2. Low serum fetuin-A levels are associated with increase markers of bone turnover and inflammation.

[Fatty acid profile in phospholipids fraction with regard to blood pressure control in the kidney transplant patients].

Introduction: Hypertension is diagnosed in over 50% of renal transplant patients, and its presence is associated with significantly increased risk of cardiovascular complications. The pathogenesis of hypertension in this group of patients is complex. The use of immunosuppressive drugs is among the most important risk factors due to their hypertension-inducing properties. It is also suspected, that fatty acids may play an important role in the development of the disease; however, the mechanism of its formation has not yet been fully elucidated. Aim: Evaluation of fatty acid profile in phospholipids fraction in the blood serum of patients after renal transplantation, with respect to the blood pressure and immunosuppressive drug used. Materials and methods: The study included 65 kidney transplant patients treated with immunosuppressants: 24 patients received CsA (9 women, 15 men) and 41 were treated with Tac (15 women, 26 men). Blood pressure level was estimated by taking an average value of the last 3 measurements in an outpatient setting. Blood pressure exceeding 140/90 mmHg was considered as abnormally high. The number of antihypertensive drugs administered was based on the analysis of patients' records and direct interviews with patients. The concentration of each fatty acid was determined using gas chromatography. Statistical analysis was performed using Statistica 10. Results: There were no statistically significant differences between both: systolic blood pressure (136.16 vs. 133.31 mmHg, p=0.499) and diastolic blood pressure (80.62 vs 80.76; p=0.962) in patients treated with CsA compared to those taking Tac. Patients treated with CsA, received ­ on average ­ more antihypertensive drugs, compared to the group of patients taking Tac (2.64 vs 2.17), but this difference was also not statistically significant (p=0.174). The profile of fatty acids in renal transplant recipients treated with CsA was similar in both with normal blood pressure and with elevated blood pressure. In case of patients treated with Tac, significantly lower concentrations of C14 (p=0.015), C16:1 (p=0.039), C18:1 (p=0.043) and MUFA (monounsaturated fatty acids; p=0.049) were found in patients with higher values of blood pressure, compared to the ones whose blood pressure was within the norm. A significantly higher concentration of fatty acids: C14 (p=0.029), C16:1 (p=0.049) and C20:5 (p=0.029) was found in patients with normal blood pressure, treated with Tac as compared with treated with CsA. In contrast, regardless to the immunosuppressive drug used, no statistically significant differences were found between the patients' groups with elevated blood pressure values. Conclusion: The prevalence of hypertension in renal transplant recipients treated with CsA and Tac is similar. The fatty acid profile in phospholipids fraction depends on the blood pressure and the immunosuppressant used.

Cardiovascular risk in chronic kidney disease patients: intima-media thickness predicts the incidence and severity of histologically assessed medial calcification in radial arteries.

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.

[Dialysis reinitiation after kidney transplant failure and preparation for retransplantation]. / Wznowienie dializ po utracie funkcji przeszczepionej nerki i przygotowanie do ponownego przeszczepienia.

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.

[Merkel cell carcinoma in patient after organ transplantation]. / Rak z komórek Merkla u chorych po transplantacji narzadów.

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.