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Cardiovascular complications such as cardiomyopathy and endothelial dysfunction, which are frequently seen in patients with acromegaly, are among the most important causes of morbidity and mortality. In this study, we aimed to investigate arterial stiffness, carotid intima-media thickness, endocan level, and A disintegrin and metalloproteinase with thrombospondin type I motif 9 level and their relationship with disease activity in patients with acromegaly with and without cardiovascular risk factors.A total of 60 patients with acromegaly-25 with active disease, 26 with well-controlled disease, and 9 with newly diagnosed disease-and 60 age-, sex-, and body mass index (BMI)-matched healthy control subjects were enrolled in this study. All the subjects' height, weight, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG) level, insulin, hemoglobin A1C (HbA1C), C-reactive protein , lipid, endocan, A disintegrin and metalloproteinase with thrombospondin type I motif 9 levels, pulse wave velocity (PWV), and carotid intima-media thickness were measured.The SBP, DBP, FPG level, HbA1C level, and PWV of the acromegaly group were higher than those of the control group. In patients with acromegaly with cardiovascular disease (CVD) risk factors, the PWV was higher than that in the control group, and in patients with acromegaly without CVD risk factors, the PWV was similar to that in the control group. In a correlation analysis, a positive correlation was found between PWV and age, BMI, SBP, DBP, FPG level, and HbA1C level in the acromegaly group.In our study, we found that arterial stiffness increased in patients with acromegaly with CVD risk factors and that increased arterial stiffness was associated with hemodynamic (SBP and DBP) and metabolic (BMI, FPG level, and HbA1C level) parameters.

Background/aim Common variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, an increased risk of autoimmune disease, malignancy, and chronic inflammation. Proteinuria is one of the most important prognostic factors causing progression in kidney disease. Proteinuria causes tubulotoxicity, activates inflammatory markers that cause fibrosis, and consequently nephropathy progression. The data is scant in the literature regarding the inflammation and nephropathy in CVID. Hence, in the present study, we aimed to investigate the relationship between tubular dysfunction, proteinuria, and inflammation in patients with CVID. Materials and methods This was a cross-sectional study involving 27 patients with CVID (15 females, 12 males; mean age, 39.88 ± 13.47 years) and 18 control subjects (10 females, 8 males; mean age, 33.83 ± 7.97 years). Patients were evaluated for kidney functions including glomerular filtration rate, fractional excretion of sodium, metabolic acidosis, serum/urine anion gap, 24-h urine proteinuria and, were grouped in terms of proteinuria. Blood samples obtained from the patients with CVID were taken into 2 mL EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD 8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique. Results Urinary density, fractional excretion of sodium, proteinuria, and metabolic acidosis are found to be higher in patients with CVID when compared to healthy controls. In the bivariate correlation analysis, proteinuria was positively correlated with age (r = 0.496, p = < 0.001), CD8+T cells percentage (r = 0.427, p = 0.02). Albumin, CRP, and CD8+T cell percentage were found to be independent variables of proteinuria. Conclusion Increased chronic ongoing inflammation was found to be associated with proteinuria in patients with CVID. Hence, in routine outpatient clinics, proteinuria should not be overlooked in this group of patients.

In the last decades several important advances have taken place in the understanding of the pathogenesis underlying membranous nephropathy, which have sparked renewed interest in its management. Four landmark trials in membranous nephropathy, and a fifth clinical trial-which was a pilot study-, have been published in the last years. The results from some of these trials have had a significant impact in the recommendations included in the 2021 Kidney Disease: Improving Global Outcomes (KDIGO) Guideline for the Management of Glomerular Diseases, which represent a significant step forward compared to the previous guideline in several aspects such as diagnosis, disease monitoring and treatment strategies. However, considering the rapidly evolving advances in the knowledge of membranous nephropathy and the recent publication of the STARMEN and RI-CYCLO trials, several recommendations contained in the guideline warrant updates. This manuscript provides a perspective of the Immunonephrology Working Group of the European Renal Association (ERA) regarding the management of membranous nephropathy in native kidneys of adult patients.

Purpose Because of the increase in globalization, clinicians all over the world are confronted the questions about safety of Ramadan fasting. However, there is no clear information about whether there is an obstacle for fasting patients with chronic disease. Hence, in the present study, we aimed to investigate the effects of Ramadan fasting on kidney and the factors affecting this relationship in patients with chronic kidney disease. Methods This study involving 117 patients [36 females, 81 males; mean age, 60 (46.0-70.0) years] with stage 2-3 chronic kidney and fasting. Patients were evaluated every 10 days for acute kidney injury (AKI) in Ramadan month. And, patients with acute kidney injury and patients without AKI were grouped. Results When the patients were evaluated for AKI, we observed that in 27 patients had acute kidney injury. While patients without AKI fasted for more days (p < 0.001), urea levels and frequency of hypertension were higher in the group with AKI (p = 0.019;p = 0.025 respectively). We also performed univariate and multiple binary logistic regression analysis to identify the risk factors of AKI. Hypertension and number of fasting day were found to be predictive of AKI (p = 0.02;p < 0.001 respectively). Conclusions We found a significant relationship between hypertension, the number of fasting days and acute kidney injury. Patients with chronic kidney damage and hypertension should be evaluated more carefully, informed about the importance of hydration after fasting and should be followed frequently for AKI.

Coronavirus disease 2019 (COVID-19) vaccine platforms are becoming available and are the most promising strategy to curb the spread of severe acute respiratory syndrome coronavirus 2 infections. However, numerous uncertainties exist regarding the pros and cons of vaccination, especially in patients with (immune-mediated) kidney diseases on immunosuppressive drugs. Here, members of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association discuss 13 frequently asked questions regarding the safety and efficacy of the most promising vaccine candidates. Post-marketing surveillance should be performed to estimate the rate of vaccine response (humoral and cellular) of different vaccine platforms and disease activity following the administration of COVID-19 vaccines. Some of the candidates induce signalling pathways, which also promote autoimmune kidney diseases, e.g. type I interferons in systemic lupus erythematosus. Efficacy estimates would thus far favour the use of selected COVID-19 vaccines, such as BNT162b2, mRNA-1273 or Gam-COVID-Vac. Humoral immune response after vaccination should be monitored using appropriate assays. Even in the absence of neutralizing antibodies, patients might be protected by a sufficient cellular immune response capable of reducing the severity of COVID-19. A reduced vaccine response after the use of CD20-depleting agents is anticipated and it is particularly important to discuss strategies to improve vaccine response with these patients. Distancing and shielding measures remain important, as not all vaccines fully protect from coronavirus infection. In-depth information about the most pressing vaccine questions is essential to reduce vaccine hesitancy of patients.

Introduction and aim Cardiovascular diseases remain the most common cause of morbidity and mortality in patients with diabetes. Epicardial adipose tissue (EAT), visceral fat depot of the heart, was found to be associated with coronary artery disease in cardiac and non-cardiac patients. Increased visceral adiposity is associated with proinflammatory activity, impaired insulin sensitivity, increased risk of atherosclerosis and high mortality. In the present study we aimed to investigate the relationship between EAT and visceral adiposity index (VAI) in patients with diabetes. Methods This was a cross-sectional study involving 128 patients with type 2 diabetes mellitus (73 females, 55 males; mean age, 54.09+±+9.17 years) and 32 control subjects (23 females, 9 males; mean age, 50.09+±+7.81 years). EAT was measured by using a trans-thoracic echocardiograph. Parameters such as waist circumference (WC), body mass index (BMI), triglyceride and high density lipoprotein (HDL) cholesterol were used to calculate VAI. Result EAT and VAI measurements were significantly higher in patients with diabetes when compared to control subjects. In the bivariate correlation analysis, VAI was positively correlated with uric acid level (r=0.214, p=0.015), white blood cell count (r= 0.262, p=0.003), platelet count (r=0.223, p=0.011) and total cholesterol levels (r= 0.363, p Conclusion Simple calculation of VAI was found to be associated with increased EAT in patients with type 2 diabetes.

Symptoms of autonomic dysfunction are common in Fabry disease. In this study we aimed to evaluate alterations in the pupillary response to white light stimulation in patients with Fabry disease and their association with the severity of autonomic symptoms. Fourteen consecutive patients with Fabry disease and 14 healthy control participants were enrolled in this cross-sectional study. The Mainz Severity Score Index (MSSI) was used to measure the severity of Fabry disease and the Composite Autonomic Symptom Scale 31 (COMPASS 31) questionnaire was used to evaluate the severity of autonomic symptoms. The pupil light responses were assessed with an infrared dynamic pupillometry unit. There were significant reductions in the amplitude (P = 0.048) and duration (P = 0.048) of pupil contraction, and the latency of pupil dilation (P = 0.048) in patients with Fabry disease compared to control subjects. The total weighted COMPASS 31 score correlated with MSSI (r = 0.592; P = 0.026) and the duration of pupil dilation (ρ = 0.561; P = 0.037). The pupillomotor weighted sub-score of the COMPASS 31 correlated inversely with the duration of pupil contraction (r = − 0.600; P = 0.023) and latency of pupil dilation (ρ = − 0.541; P = 0.046), and directly with the duration of pupil dilation (ρ = 0.877; P r = 0.533; P = 0.049). In conclusion, abnormal pupillary function is demonstrated in patients with Fabry disease, which is associated with the severity of autonomic symptoms.

Recent studies claim that FGF23 is also associated with anemia and inflammation. In this study, the relationship between FGF23 and anemia in hemodialysis (HD) and renal transplantation patients (RTx patients) patients was investigated. This was a cross-sectional study involving 40 RTx patients (13 females, 27 males; mean age, 45.93 ± 12.49 years) who had transplantation at least 6 months before, 25 HD patients (12 females, 13 males; mean age, 54.72 ± 15.5 years), and 20 healthy control subjects (13 females, 7 males; mean age, 36.7 ± 9.38 years). FGF23 was studied using Elisa method. Parameters such as iron, ferritin, total iron binding capacity, and transferrin saturation were assessed. FGF23 level was significantly higher in HD patients when compared with the RTx patients and control groups. In the bivariate correlation analysis, hemoglobin was positively correlated with albumin (r = 0.681, p = 0.000), ferritin (r = 0.446, p = 0.043), and negatively correlated with CRP (r = − 0.476, p = 0.016) and FGF23 (r = 0.493, p = 0.043). FGF23 was found to be an independent predictor of decreased hemoglobin in HD patients. In addition, this association was observed to disappear after transplantation. While FGF23 is closely related to hemoglobin levels in HD patients, we have shown that this relationship disappears after transplantation.

Sirtuins are a group of NAD-dependent enzymes that consist of seven different structural subtypes, SIRT1 to SIRT7. Sir 2 was the first sirtuin identified in Saccharomyces cerevisae. After the discovery of Sir 2 in yeast, researchers showed that these enzymes could prolong life. After the discovery of the role of prolonging life, studies were initiated to identify the members of the sirtuin family in mammals and many articles have been published on this subject up to the present. Diabetes mellitus (DM) and its complications have been increasing worldwide during the last decades despite the advancing diagnostic tools and the therapeutic applications. Hence, DM has been accepted as an epidemic worldwide. In this chapter, I aim to focus on the physiological functions of sirtuins, and thereafter I comprehensively discuss the pathophysiological roles of sirtuins in DM and related diseases, including hypertension and diabetic kidney disease (DKD). In the last part, novel treatment options regarding sirtuin activators in DM and DKD will be discussed.

Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Background and Aims Several glomerular disease registries in Europe, and they shared their data; however, there was a lack of current data on trends of primary glomerulopathy in Turkey. Glomerular disease patterns can change geographical areas and populations decade by decade. Our aim is to present Turkey's primary glomerular disease pattern from 2009 to 2017. Method 3878 native kidney biopsy records were assessed in the Turkish Society of Nephrology Glomerulopathy (TSN-GOLD) Working Group Registry. Secondary disease (lupus, etc.) and transplant biopsies do not enroll in the registry. These records divided into four periods, before 2009, 2009 to 2013, 2013 to 2017, and 2017 to current. Results A total of 3858 patients (M = 2173, K = 1685) were examined. There was no difference in the distribution of number of patients according to periods (Q1 = 968, Q2 = 960, Q3 = 968, Q4 = 962). Nephrotic syndrome was the most common biopsy indication in all quarters (58.6%, 53%, 44.1%, 51.6%, respectively). Glomerulopathy types; Membranous GN (29.9%, n = 290) was the first in Q1 and IgA nephropathy (17.7%, n = 172) was the second. IgA nephropathy (28.5%, n = 274) was the most common glomerulopathy in Q2, while Membranous GN (25.5%, n = 245) was the second most common. IgA nephropathy (29.9%, n = 285) was the most common glomerulopathy in Q3, followed by FSGS (22.9%, n = 222) and Membranous GN. In Q4, FSGS (26.8, n = 258) was the most common glomerulopathy, followed by IgA nephropathy (26.7%, n = 257) and Membranous GN (24.5%, n = 236) (Figure 1). Conclusion While biopsy indications did not change over the years, the incidence of FSGS and IgA nephropathy gradually increased.

Background and Aims The combination of new onset haematuria, proteinuria and declining GFR, often referred to as the nephritic syndrome, constitute a strong indication for renal biopsy. Several different disease entities can underlie these findings, many of them requiring prompt treatment. Epidemiological studies of glomerular diseases are in general hampered by the strong influence of differences in biopsy practices. However, there is reason to believe that such differences are less pronounced in cases of acute/subacute nephritic syndrome. The aim of the present study is to compare the frequencies of diseases causing the nephritic syndrome in Japan and Europe using data from renal biopsy registries. Method Data were retrieved from national or regional renal biopsy registries in Japan, Sweden, Norway, Scotland, Austria, Croatia and Turkey from 2007-01-01 to 2018-12-31. Only patients biopsied due to acute or subacute nephritic syndrome, defined as a combination of new onset haematuria, sub-nephrotic proteinuria and reduced GFR, were included. Demographic, clinical and laboratory data were collected from the time of renal biopsy. Results A total number of 2789 patients from Japan and 1202 patients from Europe were included. Among the Japanese patients, 46% were women, median age was 67 years (IQR 54-74) and median creatinine concentration at the time of renal biopsy was 198 µmol/L (IQR 109-343). In Europe, 43% were women, median age was 58 years (IQR 42-70) and median creatinine concentration was 210 µmol/L (IQR 127-390). Figures from the different European countries are presented in Table 1. The most common diagnosis in both Japan and Europe was ANCA-associated nephritis (44% in Japan, 34% in Europe), followed by IgA nephritis (8.5% in Japan, 18.6% in Europe) and acute tubulointerstitial nephritis (6.2% in Japan and 7.1% in Europe). Conclusion We describe preliminary data from a large multicenter cohort of patients presenting with the nephritic syndrome. This clinical presentation is most often encountered in the 6th and 7th decade of life and the distribution between men and women is fairly equal. The most common underlying cause of the nephritic syndrome in both Japan and Europe is ANCA-associated nephritis.

Background and Aims According to the data of the Turkish Society of Nephrology-Glomerular Diseases Working Group (TSN-GOLD Working Group), IgA nephropathy is the most common primary glomerular disease in Turkey. The purpose of this study was to investigate the epidemiological and clinical data of IgA nephropathy patients in Turkey. Method 4399 patients with primary glomerular diseases from 47 centers who were followed up between May 2009 and May 2019 were included in the study conducted by TSN-GOLD Working Group. 524 patients were excluded due to lack of pathological data. Among the remaining patients, demographic, clinical and laboratory data of 994 patients with IgA nephropathy were analyzed. Results The median age of the patients was 37 (28-47) years, and 37.3% of them were female. The laboratory and clinical data at the time of diagnosis is presented in Figure-1, and biopsy indications are described in Figure-2. The median number of glomeruli was 16 (IQR: 3.5-4.3), sclerotic glomeruli was 2 (IQR: 1-5), and segmental sclerotic glomeruli was 1 (IQR: 1-2). Exudative changes, subendothelial and subepithelial deposition were present in 566 patients (56.9%), 46 patients (4.6%) and in 38 patients (3.8%), respectively. 662 (66.1%) and 611 of the patients (61.4%) had tubular atrophy and interstitial fibrosis in varying degrees, respectively. 672 (%67.6) and 416 patients (%41.9) had interstitial inflammation and vascular changes, respectively. In immunofluorescence staining, 18%, 30.1%, 4.4%, 68% of the patients had IgG, IgM, C1q and C3 positivity, respectively. Crescentic glomeruli were detected in 227 patients (3.3 ± 3.1 glomeruli). Patients with crescentic glomeruli had significantly higher proteinuria and lower eGFR than the patients without [2203 mg/day (15-26078) vs 1807 mg/day (15-29112); p=0.001; 55.3 ml/min/1.73 m2 (3.72-141.9) vs 72 ml/min/1.73 m2 (3.84-150.81); p Conclusion In this study we found that, the most common presentation of IgA nephropathy patients in our country was asymptomatic urinary abnormalities followed by nephritic and nephrotic syndrome. Higher proteinuria and lower eGFR values in patients with crescentic glomeruli, support the adoption of crescentic lesions in the new Oxford classification (MEST-C) to predict more precise outcome of IgA nephropathy patients. The high number of patients to whom the Oxford classification was applied provided us with the opportunity to examine the clinical reflections of pathological features. Evaluation of the follow-up data of the patients will give us the possibility to reveal the effect of initial clinical and pathological features on clinical findings and renal outcome.

Background and Aims In IgA nephropathy (IgAN), which is characterized by mesangial IgA accumulation, there is the formation of circulating autoantibodies against galactose deficient IgA1s (Gd-IgA1). IgG / Gd-IgA1 immunocomplexes accumulate in the glomerular mesangium and play a role in the pathogenesis of IgAN. Recent studies have suggested a relationship between glomerular IgG deposition and the severity of glomerular inflammation. However, detection of the presence and severity of IgG in routine immunofluorescence microscopy (IFM) may fail. This study aims to investigate whether IgG positivity detected by IFM is associated with poor renal prognostic indicators and whether renal prognosis can be predicted according to IgG positivity. Method 4399 patients who were enrolled between May 2009-June 2019 in database of Turkish Society of Nephrology, Glomerular Diseases Working Group (TSN-GOLD) including 44 centers were evaluated. After exclusion criteria, 994 primary IgAN patients were included in the study. Glomerular IgG negative and positive patients were compared by means of Oxford classification scores, histopathological evaluations, proteinuria, creatinine, albumin, blood pressures. IgG positive patients were divided into subgroups according to the grade of the IFM positivity. The relationship between IgG positivity and poor prognosis criteria were evaluated. Results Demographic and biochemical findings of glomerular IgG positive and negative patients at the time of biopsy are shown in Table 1. No difference was found between the groups. There was no difference in the demographic and biochemical findings at the time of biopsy in IgG subgroup analyses (Table 2). There was no difference between the histopathological and Oxford MEST scores of the subgroups. Glomerular IgG positivity was not associated with diastolic blood pressure, systolic blood pressure, urea, uric acid, age, eGFR, albumin, proteinuria (p> 0.05 for all, r= -0.084, r= -0.102, r= -0.006, r=0.062, r= 0.014, r= -0.044, r= -0.061, r= -0.066, r= 0.150, respectively). Conclusion Glomerular IgG positivity detected by routine IFM in IgAN is not associated with poor renal prognostic indicators. It is difficult to predict renal prognosis by looking at the severity of IgG positivity at the baseline evaluation.

Background and Aims Rapidly progressive glomerulonephritis (RPGN) is a clinical condition that develops due to different etiologic causes, characterized by a rapid and progressive decrease in renal function and progresses to end-stage renal failure in weeks to months if not treated. In our study, diagnostic and demographic characteristics of patients diagnosed with RPGN by biopsy, clinical and laboratory findings in our country were investigated. Method Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database between May 2009 and June 2019. Demographic characteristics such as age, sex, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented is cross-sectional and includes application data for the biopsy period. According to their types, RPGN patients were classified as type 1 (anti-GBM related), type 2 (immunocomplex related) and type 3 (immune-negative; “pauci-immune”). Results After exclusion of 46 patients with missing data, 200 patients (mean age 47.9 ± 16.7 years, 44% female) were included in the study which constitutes 5.2% of the total glomerulonephritis database (total number of patients: 3875). Hypertension was present in 62 patients (31.0%) and diabetes was present in 18 patients (9.0%). Renal biopsy was performed in 147 (73.5%) patients due to nephritic syndrome (RPGN included). 80.2% of the patients' biopsies were performed in nephrology clinics and 19.8% of them were performed in radiology clinics. ANCA positivity was found in 121 (60.5%) patients (proteinase 3-ANCA was positive in 55 and myeloperoxidase-ANCA positive in 66 patients). Type 1 RPGN was detected in 11 (5.5%), type 2 RPGN in 42 (21%) and type 3 RPGN in 147 (73.5%) patients. In 21 patients (10.5%), biopsy revealed RPGN with advanced chronic changes (fibrous global sclerotic glomeruli, advanced interstitial fibrosis and tubular atrophy). Mean serum creatinine was 4.2 ± 3.4 mg/dl, median glomerular filtration rate was 18 (10-37) ml/min and proteinuria 2100 (1229-3526) mg/day according to CKD-EPI formula. The mean number of glomeruli in the biopsies was 18.8 ± 10.6 and the number of crescentic glomeruli was 9.9 ± 7.7 (ratio: 52.7%) (Figure). The patients were divided into 3 groups according to their crescentic glomeruli ratios. The proportion of crescentic glomeruli is 10-50% in group 1, 50-80% in group 2, and >80% in group 3. The demographic, laboratory and histopathological characteristics of the groups are given in Figure. It was observed that urea and creatinine increased and calcium and hemoglobin decreased with increasing crescentic glomerular ratio. Conclusion Our study provides valuable demographic, clinical, laboratory and histopathological data about RPGN in our country. Our data are generally compatible with the literature. In our study, advanced chronic histopathological findings were prominent in the biopsy of 21 patients. Early biopsy should be performed to confirm the diagnosis of RPGN and to avoid unnecessary intensive immunosuppressive therapy. In addition to the treatments applied, detailed data, including patient and renal survival are needed.

Background and Aims Fabry Disease (FD) is a lysosomal glycosphingolipid storage disorder. Kidneys are affected in FD. Despite enzyme replacement theraphy (ERT), some patient still have an ongoing deterioration of renal functions probably secondary to inappropriate immune responses. There is no data regarding NK cell subtypes and the exact relation with B-T lymphocytes and NK cells in patients with FD. We aimed to analyze subtypes of NK cells in patients with FD and compared these results with healthy subjects. Additionally, we analyzed the renal biopsy (RBx) materials of our patients prior to ERT in terms of B, T and NK cell infiltration and compared these cells in some of our FD patients after 4 years of ERT. Method 15 patients with FD and 10 healthy controls were included in the study. Of 15 patients, 8 patients were receiving agalsidase alfa or beta. Blood samples obtained from both group were taken into 2 ml EDTA tube to evaluate peripheral NK cell subgroups according to CD56 and CD16 expression and CD3, CD4, CD8 expression to determine subtypes T cells. These cells were evaluated by flow cytometry technique. The RBx of 10 patients with FD were evaluated before ERT and 3 were reevaluated after 4 years of ERT in terms of T-B, NK and plasma cells infiltration of kidney. The paraffin blocks of specimens were examined with HE, PAS, Masson-trichrome and toluidine blue staining and frozen blocks were examined with red-oil 10 staining Results The characteristics of patients with FD and healthy controls are depicted in Figure 1. Except proteinuria, there were no significant differences in terms of biochemical parameters between two groups. According to flow-cytometric analyses, total percentage of NK and T helper 1, 2, 17 and Treg cells of FD patients are similar to controls (Fig 1). When we analyzed subgroups of NK cells and determined that CD56dimCD16dimNK cells were increased, however, CD56dimCD16brightNK cells were decreased in patients with FD compared to controls (Fig1). We performed RBx of 10 patients. The percentages of CD3, 4, 8 positive Tcells, CD19, CD20 positive B cells, CD 16, 56 positive NK cells and CD 138 positive plasma cell infiltration are shown in Fig 2. According to RBx findings prior to ERT, all patients had interstistial fibrosis (IF), podocyte vacuoles (PV), podocyte inclusion (PI), CD3, CD4, CD16, CD56 positivity at different levels. In contrast, almost none of the patients had CD19, CD20, CD138 positivity. We rebiopsied 3 patients after 4 years of ERT and reevaluated specimens in terms of IF, global and segmental sclerosis (SS), PV, PI and the percentages of CD3, CD4, CD16, CD56, CD 19, CD 20, CD 138 positivity. 2 rebiopsied patients from the same family had increased serum creatinine and proteinuria despite 4 years of regular ERT. In the second biopsy of these two patients, we found that global sclerosis (GS), IF and PI are increased and abundant CD19, CD20 and CD 138 positive cells were seen which were almost absent in the first biopsy. The other patient from another family, had mildly increased proteinuria and had no creatinine increment after 4 years of ERT. In this patient, we found that GS, SS, IF, PI and arterial sclerosis were increased, however CD 3, 4, 8 positive T cells were decreased and no changes in the percentage of CD16, 56 positive NK cells. We could not demonstrate CD 19, 20, 138 positivity in the latter patient. Conclusion Our group, for the first time, demonstrated that CD56dimCD16dimsubtype of NK cells is increased in FD which is closely associated with cellular cytotoxity in normal population. Additionaly, CD 19 and CD 20 positive B cell infiltration are increased and glomerular and interstitial changes are advanced in some patients with ongoing kidney function deterioration despite 4 years of regular ERT. Hence, infiltration of Bcells in the kidneys of patients under ERT might change our therapeutic approaches in the near future. Further studies are needed to clarify the exact roles of B T and NK cells in FD.

Background and Aims Therapeutic plasma exchange (PEX) has an increasingly long list of indications in recent years, in addition to immunosuppressive therapies in many life-threatening immune activations, it provides significant improvements in mortality and morbidity. In this study, we aimed to investigate the laboratory and clinical effects of PEX performed with nephrologic indication in our clinic. Method The records of 67 patients (36 females, 31 males; mean age, 45.7±15.8 years) who underwent PEX with nephrological indication between 2012 and 2017 in our clinic were retrospectively reviewed. Characteristics of the patients such as, indications of PEX, laboratory values and number of PEX sessions were recorded. In addition, clinical responses were also evaluated. Results When a total 398 PEX sessions were examined, the most common indication (40.3%) was acute humoral rejection after renal transplantation, followed by granulomatosis with polyangiitis (19.4%) and thrombotic microangiopathy (9%), respectively. The average of the PEX sessions was 5.94. There was a statistically significant increase in the bicarbonate value when the arterial blood gas of the patients was evaluated after PEX (p=0.002). However, no significant difference was observed in the pH and ionized calcium values (p=0.135, p=0.969, respectively) (Table 1). When all the patients were evaluated, there was no significant change in hemoglobin values (p=0.174), but platelet values decreased significantly (p=0.011) after PEX. However, when the patient group admitted with thrombotic microangiopathy was examined, it was observed that platelet count increased and LDH level decreased significantly (p=0.063, p=0.028, respectively). When the serum creatinine values of all patients were evaluated, a significant decrease was observed in the serum creatinine values after PEX (p=0.001). In addition, after 2 years following PEX treatment, 70.1% of patients were still alive and 12.5% of patients undergoing PEX for acute humoral rejection were undergoing on hemodialysis treatment. Conclusion According to the results of our study, patients should be followed up especially for acid-base and electrolyte changes after PEX. In addition, therapeutic PEX might be effective in terms of improving morbidity and 2 year-mortality of these patients.

Background and Aims The largest data on the epidemiology of primary glomerular diseases (PGD) are obtained from the databases of countries or centers. Here, we presented the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD)Working Group. Method The data of patients who underwent renal biopsy and diagnosed as primary glomerular disease were recorded in the database prepared for the study. Between May 2009 and May 2019, a total of 4399 patients from 47 centers were evaluated. Basal data of 3875 patients were analyzed after exclusion of those lacking light microscopy and immunofluorescence findings. Results The mean age was 41.5 ± 14.9 years. Of the patients, 1690 were female (43.6%) and 2180 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGH was IgA nephropathy (25.7%), followed by membranous nephropathy (25.6%) and FSGS (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. Mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. Median proteinuria was 3300 (IQR: 1467-6307) mg / day, mean serum creatinine, estimated GFR and albumin values were 1.4 ± 1.5 mg / dl, 80.7 ± 39.1 ml / min and 3.2 ± 0.9 g / dl, respectively. Conclusion In Turkey, the incidence of IgA nephropathy patients have become more common than membranous nephropathy among PGD patients diagnosed with renal biopsy.

The coronavirus disease 2019 (COVID-19) pandemic has created major challenges for all countries around the globe. Retrospective studies have identified hypertension, cardiovascular disease, diabetes and older age as risk factors for high morbidity and mortality from COVID-19. There is a general concern that patients with immune-mediated kidney diseases, namely those on immunosuppressive therapies and/or those with more advanced kidney failure, could particularly be at risk for adverse outcomes due to a compromised antiviral immunity. Uncertainties exist on how management routines should be reorganized to minimize the risk of severe acute respiratory syndrome coronavirus 2 infection and what measures are necessary for infected patients. The aim of the present review of the Immunonephrology Working Group of the European Renal Association–European Dialysis and Transplant Association is to provide recommendations for the management of patients with immune-mediated kidney diseases based on the available evidence, similar circumstances with other infectious organisms and expert opinions from across Europe. Such recommendations may help to minimize the risk of encountering COVID-19 or developing complications during COVID-19 in patients with immune-mediated kidney disease.

Introduction: The aim of this study was to determine the Blastocystis prevalence and subtypes in hemodialysis patients in Turkey. Methodology: Eighty-four patients diagnosed with end-stage renal failure who were undergoing hemodialysis and 20 healthy volunteers were enrolled. Blastocystis presence was investigated by native-Lugol, trichrome staining, PCR using STS primers, and DNA sequencing analysis. Results: Among the stool samples from the hemodialysis patients, 9.52% (8/84) were found to be Blastocystis-positive with the native-Lugol and trichrome staining. Seven of the eight Blastocystis isolates were subtyped using STS primers. Blastocystis subtype distribution was as follows: one had ST1, two had ST2, two had ST3, two had ST3+ST6, and one was not subtyped. Blastocystis positivity was detected in two healthy control (2/20, %10), one subject had ST1, and the other was not subtyped. All subtypes identified by PCR were confirmed by the sequencing analysis. In the two samples that had mixed subtypes (ST3+ST6) when using the STS primers, only ST3 was detected in the sequencing analysis. Although some patients have multiple symptoms, the most common symptoms in Blastocystis positive patients were bloating (5/8), diarrhea (4/8), nausea and vomiting (2/8), and gas and weight loss (1/8). Also, only one patient had Giardia intestinalis. Conclusions: This was the first study to determine the Blastocystis subtypes in hemodialysis patients. A rare subtype, ST6, was identified in two of the patients. Thus, the ST6 infections were attributable to transmission from poultry infections. The presence of this unusual subtype suggests the need for further extensive studies of hemodialysis patients.

Background The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. Methods Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. Results The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467–6307) mg/day, 1.0 (IQR: 0.7–1.6) mg/dL, 82.9 (IQR: 47.0–113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. Conclusions The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Background: In our study, diagnostic and demographic characteristics of patients diagnosed with RPGN by biopsy, clinical and laboratory findings in our country were investigated. Methods: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. According to their types, RPGN patients were classified as type 1 (anti-GBM related), type 2 (immuncomplex related) and type 3 (pauci-immune). Results: Of 3875 patients, 200 patients with RPGN (mean age 47.9 ± 16.7 years) were included in the study which constitutes 5.2% of the total glomerulonephritis database. Renal biopsy was performed in 147 (73.5%) patients due to nephritic syndrome. ANCA positivity was found in 121 (60.5%) patients. Type 1 RPGN was detected in 11 (5.5%), type 2 RPGN in 42 (21%) and type 3 RPGN in 147 (73.5%) patients. Median serum creatinine was 3.4 (1.9–5.7) mg/dl, glomerular filtration rate was 18 (10–37) ml/min/1.73m2 and proteinuria 2100 (1229–3526) mg/day. The number of crescentic glomeruli ratio was ratio 52.7%. It was observed that urea and creatinine increased and calcium and hemoglobin decreased with increasing crescentic glomerular ratio. Conclusions: Our data are generally compatible with the literature. Advanced chronic histopathological findings were prominent in the biopsy of 21 patients. Early biopsy should be performed to confirm the diagnosis of RPGN and to avoid unnecessary intensive immunosuppressive therapy. In addition to the treatments applied, detailed data, including patient and renal survival, are needed. © 2020, Japanese Society of Nephrology.

Fabry disease is characterised by neuropathic pain and accelerated vascular disease. This study evaluates the utility of corneal confocal microscopy (CCM) to non-invasively quantify corneal nerve and endothelial cell morphology and dendritic cell (DC) density in relation to disease severity in subjects with Fabry disease. Seventeen consecutive participants with Fabry disease and 17 healthy control subjects were included in this cross-sectional study. Fabry disease severity was measured using the Mainz Severity Score Index (MSSI). Central corneal sensitivity was assessed with a contact corneal esthesiometer. There was a significant reduction in the corneal sensitivity (5.75 [5.25–6.00] vs. 6.00 [6.00-6.00] cm, P = 0.014), nerve fiber density (NFD) (26.4 ± 10.1 vs. 33.7 ± 7.9 fibers/mm2, P = 0.025) and nerve fiber length (NFL) (15.9 ± 3.4 vs. 19.5 ± 4.4 mm/mm2, P = 0.012) and an increase in DC density (38.3 [17.5–97.3] vs. 13.5 [0–29.4] cells/mm2, P = 0.004) in subjects with Fabry disease compared to the healthy control subjects. The total MSSI score correlated with NFD (ρ = −0.686; P = 0.006), NFL (ρ = −0.692; P = 0.006), endothelial cell density (ρ = −0.511; P = 0.036), endothelial cell area (ρ = 0.514; P = 0.036) and α-galactosidase A enzyme activity (ρ = −0.723; P = 0.008). This study demonstrates reduced corneal sensitivity, corneal nerve fiber damage and increased DCs in subjects with Fabry disease.

Renal transplantation is the most effective treatment modality for end-stage renal failure. According to the Ministry of Health Organ Transplant Registration System, despite the presence of 14,936 renal transplant recipients in Turkey, there are not enough data about the prognosis of these patients. Therefore, we aimed to ascertain the rate of patients returning to hemodialysis (HD) due to nonfunctioning graft in our country. One thousand four hundred and ninety-eight (males: 826, females: 672) HD patients who undergo HD at 22 HD centers in total, from different geographical regions to represent our country were examined retrospectively. The informations were obtained from patient registry files and anamnesis which were in HD centers. The number of patients returning to HD due to the loss of graft function was 77 (males: 56, females: 21). Eleven of the patients had transplantation from cadavers (14%) and 66 from living donors (86%). Prevelance of patients, who return to HD after the failure of renal transplantation, between HD patients was 5.1. The mean duration of return to HD after renal transplantation was 6.7 ± 5.9 years for all patients. There was no significant difference in the duration without HD after transplantation between two groups when cadaveric and living donor transplants were compared (P = 0.759). There was no statistically significant difference in duration without HD after transplantation between patients receiving HD treatment before transplantation and preemptive transplant (P = 0.212). The prevelance of patients, who return to HD due to nonfunctioning graft among HD patients was 5.1. The duration without HD were similar after transplantation from both cadavers and living donors. The duration without HD was found longer among those who were operated before 2000.

Hemodialysis patients have extremely increased cardiovascular mortality. The coronary artery calcification score (CACS) in uremic patients receiving hemodialysis reflects the severity of atherosclerotic vascular disease and predicts the cardiovascular events. In cardiac conditions, left atrial (LA) size has a prognostic importance. In this study, relationship between coronary artery calcification and left atrial size was investigated. This was a cross-sectional study involving 32 hemodialysis patients (16 females, 16 males; mean age, 52.4 ± 14.1 years) receiving HD for ≥6 months. Coronary artery calcium scoring was performed by a 16-MDCT scanner, and CACS was calculated by Agatston score. A calcification was defined as a minimum of two adjacent pixels (>0.52 mm2) with a density over 130 Hounsfield units. Patients were divided into two subgroups (group 1: CACS ≤ 45.85, n = 16 and group 2: CACS > 45.85, n = 16) according to median CACS value. Mean CACS value of 32 hemodialysis patients was 245.57 ± 373.91. LA size was significantly higher in patients with CACS > 45.85 (group 2) than in patients with CACS ≤ 45.85 (group 1). In the bivariate correlation analysis, total CACS was positively correlated with left atrium size (r = 0.47, p = 0.006). Total CACS was positively correlated with age (r = 0.43, p = 0.014). LA size was positively correlated with diastolic blood pressure (r = 0.42, p = 0.016) and negatively correlated with ejection fraction (r = −0.42, p = 0.016). The clinical parameters such as BMI, duration of dialysis, blood pressure, ejection fraction, serum levels of calcium, phosphorus, uric acid, albumin, CRP, triglyceride, cholesterol, hemoglobin and ferritin were not independently associated with total CACS. We found a positive relationship between the CACS and LA size measured by echocardiography in hemodialysis patients. Therefore; echocardiography, which is cheaper and non-invasive than tomographic examinations, might be considered for the risk stratification of coronary artery disease in hemodialysis patients.

Diabetic kidney disease (DKD) can occur in approximately 30-40% of both type 1 and type 2 diabetic patients. The well-established features of DKD include increased serum glucose levels along with chronic low-grade inflammation, OxS, increased advanced glycation end products, sorbitol accumulation, increased hexosamine, and protein kinase C pathway activation. On the other hand, accumulating evidence suggests that novel pathways including apoptosis and autophagy might also play important roles in the pathogenesis and progression of DKD. In this review, the integrated mechanisms of inflammation, oxidative stress, apoptosis, and autophagy are discussed in the pathogenesis as well as progression of DM and DKD.

WOS: 000390981200011, PubMed: 28144263, Introduction: Chronic inflammation is a major risk factor in the pathogenesis of cardiovascular disease in end-stage renal disease (ESRD) patients. Epicardial adipose tissue (EAT) is the true visceral fat depot of the heart. The relationship between coronary artery disease and EAT was shown in healthy subjects and ESRD patients. In the present study we aimed to investigate the relationship between EAT and inflammation parameters including neutrophil-to-lymphocyte ratio (NLR) in hemodialysis (HD) patients. Material and methods: Forty-three HD patients (25 females, 18 males; mean age: 64.1 11.9 years) receiving HD and 30 healthy subjects (15 females, 15 males; mean age: 59.1 +/- 10.8 years) were enrolled in the study. Epicardial adipose tissue measurements were performed by echocardiography. Results: Neutrophil-to-lymphocyte ratio levels were significantly higher in HD patients than in the healthy control group. Hemodialysis patients were separated into two groups according to their median value of NLR (group 1, NLR < 3.07 (n = 21) and group 2, NLR 3.07 (n = 22)). Group 2 patients had significantly higher EAT, C-reactive protein and ferritin levels, while albumin levels were significantly lower in this group. In the bivariate correlation analysis, EAT was positively correlated with NLR (r = 0.600, p < 0.001) and ferritin (r = 0.485, p = 0.001) levels. Conclusions: Neutrophil-to-lymphocyte ratio was found to be an independent predictor of EAT in HD patients (odds ratio = 3.178; p = 0.008). We concluded that this relationship might be attributed to increased inflammation in uremic patients.

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. Objective: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. Methods: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. Results: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. Conclusions: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease. (C) 2019 S. Karger AG, Basel C1 [Yalin, Serkan Feyyaz; Senates, Banu Erkalma; Oruc, Meric; Altiparmak, Mehmet Riza; Seyahi, Nurhan] Istanbul Univ Cerrahpasa, Cerrahpasa Med Fac, Dept Nephrol, Istanbul, Turkey. [Eren, Necmi] Kocaeli Univ, Dept Nephrol, Med Fac, Kocaeli, Turkey. [Sinangil, Ayse; Ecder, Tevfik] Bilim Univ, Dept Nephrol, Med Fac Med, Istanbul, Turkey. [Yilmaz, Vural Taner; Kocak, Huseyin] Akdeniz Univ, Div Nephrol, Med Fac, Antalya, Turkey. [Tatar, Erhan; Uslu, Adam] Bozyaka Training & Res Hosp, Dept Nephrol, Izmir, Turkey. [Ucarf, Ali Riza; Demir, Erol; Caliskan, Yasar; Turkmen, Aydin] Istanbul Univ, Fac Med, Div Nephrol, Istanbul, Turkey. [Sevinc, Mustafa; Basturk, Taner] Sisli Hamidiye Etfal Training & Res Hosp, Dept Nephrol, Istanbul, Turkey. [Can, Ozgur; Ogutmen, Melike Betul] Haydarpasa Training & Res Hosp, Dept Nephrol, Istanbul, Turkey. [Gurkan, Alp; Kinalp, Can] Medicana, Dept Nephrol, Istanbul, Turkey. [Arik, Nurol] Ondokuz Mayis Univ, Dept Nephrol, Med Fac, Samsun, Turkey. [Ecder, Sabahat Alisir] Medeniyet Univ, Div Nephrol, Goztepe Training & Res Hosp, Istanbul, Turkey. [Uyar, Murathan] Gaziosmanpasa Hosp, Dept Nephrol, Istanbul, Turkey. [Yasar, Murat; Dursun, Belda] Pamukkale Univ, Dept Nephrol, Med Fac, Denizli, Turkey. [Gulcicek, Sibel] Istanbul Training & Res Hosp, Dept Nephrol, Istanbul, Turkey. [Mese, Meral; Bahcebasi, Zerrin Bicik] Dr Lufti Kirdar Kartal Training & Res Hosp, Dept Nephrol, Istanbul, Turkey. [Dheir, Hamad; Sipahi, Savas; Genc, Ahmed] Sakarya Univ, Dept Nephrol, Tip Med Fac, Sakarya, Turkey. [Cakir, Ulkem] Acibadem Univ, Dept Nephrol, Med Fac, Istanbul, Turkey. [Cevher, Simal Koksal; Dede, Fatih] Ankara Numune Training & Res Hosp, Dept Nephrol, Ankara, Turkey. [Turkmen, Kultigin] Necmettin Erbakan Univ, Div Nephrol, Meram Med Fac, Konya, Turkey. [Guven, Bahtisen] Bahcesehir Univ, Dept Nephrol, Med Fac, Istanbul, Turkey. [Taymez, Dilek Guven] Kocaeli State Hosp, Dept Nephrol, Kocaeli, Turkey. [Yelken, Berna] Mem Hosp, Dept Nephrol, Istanbul, Turkey.

Background: Vasculopathy is a major cause of mortality and morbidity in Behcet’s Disease (BD). Subclinical atherosclerosis can even be detected in the early stage of BD. Soluble tumor necrosis factor-like (TNF) weak inducer of apoptosis (TWEAK) is known as a good marker of the inflammation in vascular tree. The aim of this study is to examine the relationship between carotid artery intima-media thickness (cIMT) and serum TWEAK levels in patients with BD. Materials and Methods: In line with International BD Study Group criteria, 48 BD, and 30 controls were included in our study. Disease activity was evaluated according to BD current activity form (BDCAF). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), lipid parameters, serum TWEAK levels, and cIMT were measured. Results: Disease activity score of BD patients was found as 2 (range 0–7). cIMT, serum TWEAK, CRP and ESR levels of BD patients were significantly higher comparing to cIMT (0.62 ± 0.13 mm vs. 0.43 ± 0.09 mm, p < 0.001), serum TWEAK (667.5 ± 130.6 vs. 603.4 ± 89.6 pg/ml, p = 0.015), CRP (3.9 ± 4.3 vs. 1.4 ± 1.0 mg/dl, p < 0.001) and ESR (10.2 ± 10.0 vs. 5.6 ± 3.7 mm/h, p = 0.005) levels of the control group. There was a positive correlation between serum TWEAK level and disease activity (r = 0.251, p = 0.030) and cIMT (r = 0.463, p < 0.001). Our study also revealed an independent correlation between cIMT and serum TWEAK levels (beta = 0.354, p < 0.001). Conclusion: Increased serum TWEAK levels can play a part in the development of atherosclerotic heart disease in BD. Due to their liability to atherosclerosis, patients with BD must followed closely.

The most important cause of anemia in CKD is relative deficiency of erythropoietin (EPO) secretion from the diseased kidney and EPO therapy has become the standard treatment for anemia of CKD. However, some patients do not respond well to erythropoiesis stimulating agent (ESA), so-called ESA resistance. One of the most important causes of ESA resistance is chronic inflammation in hemodialysis (HD) patients. ESA hyporesponsiveness index (EHRI), calculated as the weekly dose of EPO divided by kilograms of body weight divided by the hemoglobin level, and has been considered useful to assess the EPO resistance. Neutrophil/lymphocyte (NLR) ratio and platelet/lymphocyte ratio (PLR) were also found to be associated with inflammation in HD patients. However, the relationship between NLR, PLR and EHRI has not been investigated before. HD patients underwent medical history taking, physical examination, calculation of dialysis adequacy and biochemical analysis and calculation of EHRI. Logarithmically converted EHRI (logEHRI) was correlated only with hemoglobin (r -0.381, P < 0.0001) and PLR (r = 0.227, P = 0.021) but not with NLR. Comparison of PLR among 25th, 50th and 75th percentile of EHRI showed that PLR levels increased going from the 25th to 75(th) percentile (P = 0.032). Posthoc analysis revealed that 25-75th percentile (P = 0.014) and 50-75th percentile (P = 0.033) were different with respect to PLR. In linear regression analysis, PLR (standardized β = 0.296, confidence interval: 0.000-0.001, P = 0.003) was independently associated with logEHRI. We found that PLR was independently associated with EHRI in HD patients. PLR, which is quite a simple and cheap method, may guide clinicians for detecting EPO resistance.

Left atrium (LA) mechanical functions and atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity in general population. Data are scant about these parameters in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) and peritoneal dialysis (PD). We aimed to evaluate AEMD times and LA mechanical functions and associated risk factors in HD and PD patients. Forty-four healthy individuals, 62 HD and 50 PD patients were enrolled in the study. Echocardiography was performed before midweek dialysis session for HD patients and on admission for PD patients. Data were expressed as mean ± SD. Spearman’s test was used to assess linear associations. Predictors of left intra-atrial EMD time and LA active emptying volume (LAaeV) were assessed by regression analysis. Left intra-atrial-AEMD times were significantly longer in HD patients compared to PD patients. LAaeV was positively correlated with inter-atrial time, left intra-atrial time, systolic and diastolic BP, calcium and neutrophil-to-lymphocyte ratio (NLR) (r 0.22, p 0.016; r 0.28, p 0.002; r 0.34, p

WOS: 000392937800028 PubMed ID: 28006774 Background/Aims: Fabry disease is a treatable cause of chronic kidney disease (CKD) characterized by a genetic deficiency of a-galactosidase A. European Renal Best Practice (ERBP) recommends screening for Fabry disease in CKD patients. However, this is based on expert opinion and there are no reports of the prevalence of Fabry disease in stage 1-5 CKD. Hence, we investigated the prevalence of Fabry disease in CKD patients not receiving renal replacement therapy. Methods: This prospective study assessed a-galactosidase activity in dried blood spots in 313 stage 1-5 CKD patients, 167 males, between ages of 18-70 years whose etiology of CKD was unknown and were not receiving renal replacement therapy. The diagnosis was confirmed by GLA gene mutation analysis. Results: Three (all males) of 313 CKD patients (0.95%) were diagnosed of Fabry disease, for a prevalence in males of 1.80%. Family screening identified 8 aditional Fabry patients with CKD. Of a total of 11 Fabry patients, 7 were male and started enzyme replacement therapy and 4 were female. The most frequent manifestations in male patients were fatigue (100%), tinnitus, vertigo, acroparesthesia, hypohidrosis, cornea verticillata and angiokeratoma (all 85%), heat intolerance (71%), and abdominal pain (57%). The most frequent manifestations in female patients were fatigue and cornea verticillata (50%), and tinnitus, vertigo and angiokeratoma (25%). Three patients had severe episodic abdominal pain attacks and proteinuria, and were misdiagnosed as familial Mediterranean fever. Conclusions: The prevalence of Fa bry disease in selected CKD patients is in the range found among renal replacement therapy patients, but the disease is diagnosed at an earlier, treatable stage. These data support the ERBP recommendation to screen for Fabry disease in patients with CKD of unknown origin. (C) 2016 The Author(s) Published by S. Karger AG, Basel Sanofi Genzyme Corporation; Intensificacion ISCIII and REDINREN [RD012/0021] We are indebted to our patients and their families for volunteering to contribute their medical information to the physicians who are dedicated to their care. This work was supported by grants from Sanofi Genzyme Corporation. The lead investigator had full access to all data in the study. All investigators take responsibility for the accuracy of the individual data that they entered in the system provided by FMF Arthritis Vasculitis and Orphan disease Research (FAVOR). AO was supported by Intensificacion ISCIII and REDINREN RD012/0021.

Introduction: Acute kidney injury (AKI) is an important complication of cardiac surgery due to its high mortality. The aim of the present study was to detect the factors leading to AKI in patients who underwent coronary artery bypass surgery (CABS) and also to determine the optimal timing for detecting AKI using the biomarker neutrophil gelatinase-associated lipocalin (NGAL). Materials and Methods: The records of 375 patients who underwent CABS were reviewed in this case-control study. Ejection fraction (EF), common carotid artery intima-media thickness (CCA-IMT) and cross-clamp (C-C) time of the patients were recorded. Blood samples were taken from all patients on preoperative day 1 as well as 6, 12, 24, 36, 48 h and 7 days after operation. Biochemical parameters were studied in patients with and without AKI. Results: According to the Risk Injury Failure Loss End Stage criteria, 24 patients had renal risk, 17 had injury and 4 had failure. Postoperative 24-hour serum creatinine levels indicated the risk of renal dysfunction for only 4 patients in the AKI group. CCA-IMT, C-C time, haematocrit (HCT) and preoperative interleukin-6 levels were significantly higher in the AKI group than in the non-AKI group. Postoperative 6- and 12-hour NGAL levels in the AKI group correlated with postoperative 36-hour serum creatinine levels. The optimal cut-off values for postoperative 6- and 12-hour NGAL test were 310 and 283 ng/ml, respectively. The area under the curve was higher in the 12-hour NGAL test (p < 0.0086). Conclusion: The number of stenotic coronary arteries, EF, CCA-IMT and HCT are all important risk factors. Early postoperative NGAL results were highly specific for the early recognition of AKI.

Background: Diabetic nephropathy is the most common cause of end-stage renal disease. Emerging evidences indicate that many mechanistic pathways including apoptosis play an important role in the pathogenesis and progression of macrovascular and microvascular complications of diabetes mellitus. The aim of the present study is to show the effects of grape seed extract (GSE) on oxidative stress and apoptosis in the kidney of streptozotocin-induced diabetic rats. Materials and methods: The study included control group, diabetic group without treatment and diabetic group treated with GSE (n=7) group. GSE was given orally (100 mg/kg/day) for six weeks. Following parameters were evaluated; oxidative stress index, caspase 1, IL1-alpha, caspase 2, IL1-beta, BCL2-associated agonist of cell death (BAD), X-linked inhibitor of apoptosis (XIAP), DNA fragmentation factor, alpha subunit and beta bubunit (DFFA, DFFB), BH3 interacting domain death agonist (BID), caspase 6, Bcl2-like 1 (BCL-XL), caspase 8, tumor necrosis factor receptor superfamily, member 1 b (TNFRSF1B) and IAP-binding mitochondrial protein (DIABLO). Results: Oxidative stress index levels were significantly increased in the kidney of diabetic group without treatment compared to control group, and decreased in diabetic + GSE group compared to diabetic group without treatment. In the kidney of diabetic group without treatment, caspase 1, IL-1 alpha, BAD, DFFA, DFFB and caspase-6 gene expressions were significantly higher compared to control group. In diabetic + GSE group caspase 1, caspase 2, XIAP, DFFA, BID, BCL-XL and TNFRSF1B genes were significantly decreased compared to control group. Conclusions: Grape seed reduces oxidative stress and apoptosis gene expression suggesting the protective effect on diabetic nephropathy. © 2015 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted

Background/Objective: Elevated pulse wave velocity (PWV) and central aortic blood pressures are independent predictors of increased cardiovascular morbidity and mortality in hemodialysis (HD) patients. Oxalic acid is a uremic retention molecule that is extensively studied in the pathogenesis of calcium oxalate stones. Oxalobacter formigenes, a member of the colon microbiota, has important roles in oxalate homeostasis. Data regarding the colonization by and the exact role of O. formigenes in the pathogenesis of oxalic acid metabolism in HD patients are scant. Hence, we aimed to determine the relationship between fecal O. formigenes colonization, serum oxalic acid and hemodynamic parameters in HD patients with regard to the colo-reno-cardiac axis. Methods: Fifty HD patients were enrolled in this study. PWV and central aortic systolic (cASBP) and diastolic blood pressures (cADBP) were measured with a Mobil-O-Graph (I.E.M. GmbH, Stolberg, Germany). Serum oxalic acid levels were assessed by ELISA, and fecal O. formigenes DNA levels were isolated and measured by real-time PCR. Results: Isolation of fecal O. formigenes was found in only 2 HD patients. One of them had 113,609 copies/ml, the other one had 1,056 copies/ml. Serum oxalic acid levels were found to be positively correlated with PWV (r = 0.29, p = 0.03), cASBP (r = 0.33, p = 0.001) and cADBP (r = 0.42, p = 0.002) and negatively correlated with LDL (r = -0.30, p = 0.03). In multivariate linear regression analysis, PWV was independently predicted by oxalic acid, glucose and triglyceride. Conclusions: This is the first study that demonstrates the absence of O. formigenes as well as a relation between serum oxalic acid and cASBP, cADBP and PWV in HD patients. Replacement of O. formigenes with pre- and probiotics might decrease serum oxalic acid levels and improve cardiovascular outcomes in HD patients.

Background: Atrial electromechanical delay (AEMD) times were considered independent predictors of cardiovascular morbidity among the general population. We aimed at evaluating AEMD times and other risk factors associated with 2-year combined cardiovascular (CV) events in HD patients. Material and Methods: Sixty hemodialysis (HD) and 44 healthy individuals were enrolled in this prospective study. Echocardiography was performed before the mid-week dialysis session for HD patients. Data were expressed as mean ± SD. Spearman test was used to assess linear associations. Survival was examined with the Kaplan-Meier method. Multivariate Cox regression analysis was used to determine the predictors of combined CV events in this cohort. Results: At the beginning of the study, left intra-atrial-AEMD times were significantly longer in HD patients compared to the left intra-atrial-AEMD times in healthy individuals. After 24 months, 41 patients were still on HD treatment and 19 (31.6%) had died. Serum triglyceride, total cholesterol and albumin were found to be higher and C-reactive protein (CRP) levels, left intra-atrial EMD time (LIAT) and interatrial EMD times were found to be lower in survived HD patients. With the cut-off median values of 3.5 g/dl for albumin, 0.87 mg/dl for CRP, 157 mg/dl for total cholesterol and 151 mg/dl for triglyceride, the Kaplan-Meier curves demonstrated significant differences in terms of all-cause mortality. We also demonstrated the Kaplan-Meier survival curves of HD patients according to tertile values of LIAT. Cox regression analysis revealed that increased CRP and higher LIAT were found to be independent predictors of combined CV events. Conclusions: Increased LIAT and inflammation were found to be closely associated with 2 years combined CV events and all-cause mortality in HD patients.

Acute kidney injury (AKI) is a common complication of cardiac surgery developing in 25-35% cases. Recently, neutrophil gelatinase-associated lipocalin (NGAL) was shown to predict AKI development earlier than serum creatinine. Some studies demonstrated the predictive role of post-operative serum uric acid (SUA) as an early marker of AKI. We aimed to study the role of serum and urine NGAL as well as SUA to predict progression of AKI.This is a prospective observational study of patients undergoing cardiac surgery. Blood and urine samples for measurement of uric acid, serum and urine NGAL levels were collected prior to cardiac surgery (0 h), and in the time course at 2nd and 24th hours after surgery. Patients who developed AKI were divided into two subgroups as progressing and non-progressing AKI.Sixty patients (42 males, 18 females) were included. After cardiac surgery, 40 patients developed AKI, 20 of whom non-progressing AKI, and 20 progressing AKI. All of the markers significantly increased in AKI patients. A receiver operator characteristics (ROC) curve analysis showed higher predictive ability of SUA for progressing AKI compared with serum and urine NGAL. When compared markers obtained at the second hour after surgery, UA had significantly large AUC than NGAL to predict AKI developed at 24 and 48 h, particularly in patients, who require renal replacement therapy (RRT).Uric acid seems to predict the progression of AKI and RRT requirement in patients underwent cardiac surgery better than NGAL.

Common variable immunodeficiency (CVID) is a heterogeneous primary deficiency characterized by hypogammaglobulinemia, recurrent infections, and an increased risk of autoimmune disease and malignancy, and so chronic inflammation. Cardiovascular disease is the leading cause of mortality in the general population. Recent studies have suggested that chronic inflammation is an important player in the pathogenesis of CVID. Accelerated atherosclerosis due to ongoing inflammation from recurrent infections and autoimmunity is an expected clinical entity in patients with CVID. However, cardiovascular mortality as a cause of death in CVID series is either absent or minor. We hypothesized that accelerated atherosclerosis and cardiovascular disease are overlooked by clinicians, or atherosclerosis is really lower than that in the general population that may be prevented by some factors such as life-long immunoglobulin replacement treatment.

Chronic inflammation was found to be correlated with coronary (CAC) and thoracic peri-aortic calcification (TAC) in end-stage renal disease (ESRD) patients. Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in cardiac and noncardiac disorders. Data regarding NLR and its association with TAC and CAC are lacking. We aimed to determine the relationship between NLR and vascular calcification in ESRD patients. This was a cross-sectional study involving 56 ESRD patients (22 females, 34 males; mean age, 49.9 ± 14.2 years) receiving peritoneal dialysis or hemodialysis for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. TAC and CAC scores were measured by using an electrocardiogram-gated 64-multidetector computed tomography. NLR was calculated as the ratio of the neutrophils and lymphocytes. There was a statistically significant correlation between NLR, TACS and CACS in ESRD patients (r = 0.43, P = 0.001 and r = 0.30, P = 0.02, respectively). The stepwise linear regression analysis revealed that age, as well as NLR were independent predictors of TACS. However, increased age was the only independent predictor of CACS according to linear regression analysis. Simple calculation of NLR can predict vascular calcification in ESRD patients.

Kardiyovasküler hastalıklar ve endotelyal disfonksiyon son dönem böbrek yetmezliği hastalarında en önemli ölüm nedenleridir. Periton diyalizi ve hemodiyaliz gibi tedavi yöntemlerinin farklı parametreler üzerine farklı etkileri vardır. Asimetrik dimetilarjinin endojen nitrik oksit sentaz inhibitörüdür ve kronik böbrek yetmezliğinin progresyonunda yeni bir belirteç olduğu gösterilmiştir. Homosistein endotel hasarı, damar düz kas hücre proliferasyonu ve koagülasyon anormallikleri yoluyla trombogenez ve atero- geneze neden olur. Daha önceki çalışmalarda periton diyalizi (PD) ve hemodiyalizin (HD) oksidan ve antioksidan sistemler üzerine etkisiyle ilgili çelişkili bulgular vardır. Bu çalışmada HD, PD ve sağlıklı kişilerde ADMA, homosistein ve CRP düzeylerini belirlemeyi amaçladık. Çalışmaya 44 PD (23E,21K), 26HD (13E,13K) hastası ve 29 (15E,14K) sağlıklı kişi katıldı. ADMA, homosistein, arjinin ve CRP düzeyleri ölçüldü. Son dönem böbrek yetmezliği (SDBY) hastalarının ADMA, homosistein ve CRP düzeyleri sağlıklı kontrol grubuna göre yüksek (p0.001), arjinin düzeyleri düşük olarak bulundu(p0.001). HD ve PD gruplarında ADMA, homosistein ve CRP seviyeleri açısından farklılık bulunamadı (sırasıyla p:0.287, p: 0.587, p: 0.835) Bizim sonuçlarımız HD,PD hastalarında sağlıklı kontrole göre ADMA ve homosistein düzeylerinin yüseldiğini gösterdi. Bu bulgular; diyaliz hastalarında endotel disfonksiyonu, inflamasyon ve oksidatif stresin arttığını ve ADMA ve homosistein düzeylerinin diyaliz tedavi yönteminden etkilenmediğini göstermektedir., Cardiovascular diseases and endothelial disfunction are major causes of mortality in patients with end stage renal disease (ESRD). Treatment strategies like continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) have different effects on dif- ferent parameters. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide (NO) synthase inhibitor and it has been reported to be a novel marker for the progression of chronic kidney disease (CKD). Homocysteine is believed to cause atherogen- esis and thrombogenesis via endothelial damage, vascular smooth muscle proliferation and coagulation abnormalities. In previ- ous studies, conflicting findings have been reported about the effect of HD and CAPD on oxidant and antioxidant systems. In this study, we aimed to investigate ADMA, homocysteine and C- reactive protein (CRP) levels in patients with ESRD having HD and CAPD treatment and healthy individuals. This study was performed on 44 (23M, 21F) CAPD patients, 26 (13M, 13F) HD patients and 29 (15M, 14F) age and sex matched healthy control subjects. The lipid profile, ADMA, homocysteine, arginine and CRP levels were measured. Serum ADMA, homocysteine and CRP levels of the ESRD patients were significantly higher, whereas serum arginine levels were significantly lower in both HD and CAPD patients compared to control subjects. No differences were found between serum ADMA, homocysteine and CRP levels of the CAPD and HD patients. Our results suggest that ADMA, homocysteine and CRP levels were increased in HD and CAPD patients compared to the control subjects. These findings suggest that ESRD patients are prone to inflammation, oxidative stress and endothelial dysfunction. We conclude that endothelial dysfunction, inflammation and oxidative stress are increased in dialysis patients and ADMA concentrations are not affected by the modality of dialysis treatment.

Neutrophil-to-lymphocyte ratio (NLR) was introduced as a potential marker to determine inflammation in end-stage renal disease (ESRD) patients. Recently, platelet-to-lymphocyte ratio (PLR) and NLR were found to positively correlated with inflammatory markers including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 in cardiac and noncardiac patients. Data regarding PLR and its association with inflammation are lacking in hemodialysis (HD) and peritoneal dialysis (PD) patients. Hence, we aimed to determine the relationship between PLR, NLR, and inflammation in ESRD patients. This was a cross-sectional study involving 62 ESRD patients (29 females, 33 males; mean age, 49.6 ± 14.6 years) receiving PD or HD for ≥6 months in the Dialysis Unit of Necmettin Erbakan University. PLR, NLR, C-reactive protein, TNF-α, IL-6 levels were measured. PLR, NLR, serum high sensitive C-reactive protein, IL-6, and TNF-α levels were significantly higher in PD patients when compared with HD patients. ESRD patients with PLR ≥ 140 had significantly higher NLR, IL-6, and TNF-α levels when compared to patients with PLR

ObJEcTIVE: Recombinant human erythropoietin (r-HuEPO) was found to be associated with increased blood pressure in hemodialysis (HD) patients. Plasma endothelin-1(ET-1) was reported to be increased during treatment with r-huEPO in HD patients. Prostacyclin (PGI2) was found to be associated with the reduction in vascular resistance. We aimed to determine the role of ET-1 and PGI2 on r-huEPO-induced hypertension in HD patients.