Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome.

Introduction. The aim was to evaluate the effect of therapeutic plasma exchange (TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome (aHUS), and additionally, to examine the reliability of discontinuation of eculizumab treatment.Methods. This was an observational and retrospective study of 18 patients diagnosed with aHUS.Results. The median age of the study population was 30 (22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3 (66%) patients for TPE and 5 of 9 (56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS developed disease relapse after Eculizumab discontinuation.Conclusion. Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.

Determination of genotoxic effects in hemodialysis patients with chronic kidney disease and the role of diabetes mellitus and other biochemical parameters.

Chronic kidney disease (CKD) is a common health problem. The primary etiology of CKD is diabetes mellitus (DM). The aim of our study is to determine the possible role of DM and also effects of other factors such as hypertension, duration of hemodialysis (HD), age, sex, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin on genetic alterations in maintenance HD patients using chromosomal aberrations (CAs), sister chromatid exchanges (SCEs), and micronucleus (MN) tests. According to the results, the frequency of CAs (p = 0.001), SCEs (p < 0.001) and MN (p < 0.001) statistically increased in HD patients compared to controls. However, there was no significant effect of diabetes as well as other factors on CA, SCE (except at factor of age), and MN in HD patients compared to controls. The mitotic (MI), replication (RI) and nuclear division indices (NDI) significantly decreased in HD patients compared to controls (p < 0.001). In addition, RI (p < 0.001) and NDI (p = 0.047) were significantly decreased in diabetic HD patients than the non-diabetic HD patients. There was no relation between the frequency of CA, SCE and MN and duration of HD treatment with correlation analysis. According to univariate regression analyses, only having CKD was significantly associated with the values of CA, SCE and MN. However, in multivariate analyses, only having CKD remained as significantly associated with CA, SCE and MN values. Consequently, the clastogenic and mutagenic effects increased in HD patients compared to controls; unlike DM in which cell proliferation decreased.

Oral Candida Colonization as a Risk Factor for Chronic Inflammation and Atherosclerosis in Hemodialysis Patients.

The purpose of this study was to determine the prevalence of oral Candida spp. in HD patients and to investigate its relation with systemic inflammation and atherosclerosis. Microbiological samples were taken from buccal mucosa, palate, and dental prosthesis with a cotton swab. High-sensitivity CRP (hsCRP) and IL-6 were measured as inflammation markers. A total of 69 patients (58% male and median age 62 years) were enrolled in this study; 53.6% of total patients had oral Candida colonization. HsCRP and IL-6 levels were found to be significantly higher in the oral Candida colonization positive group than in the Candida colonization negative group (P = 0.002 and P = 0.01, respectively). HDL levels were significantly lower in the Candida colonization positive group (P = 0.03). Peripheral artery disease (P = 0.05) and oral Candida colonization (P = 0.002) were significantly associated with inflammation. In addition to conventional risk factors such as age (P = 0.03), diabetes (P = 0.001), and peripheral artery disease (P = 0.002), oral Candida colonization is associated with coronary artery disease (P = 0.04). Oral Candida colonization might be associated with chronic inflammation and development of atherosclerosis in HD patients.

DNA damage in hemodialysis patients with chronic kidney disease; a test of the role of diabetes mellitus; a comet assay investigation.

The incidence of chronic kidney disease (CKD) is increasing rapidly. Diabetes mellitus (DM) is the most important cause of CKD. We studied the possible role of DM in CKD patients with respect to DNA damage, as assessed by the comet assay in 60 CKD patients (with or without DM) undergoing hemodialysis and in 26 controls. Effects of other factors, such as age, sex, hypertension, duration of hemodialysis, body mass index (BMI), and levels of hemoglobin (HB), intact parathormone (iPTH), and ferritin (FER), were also examined. Primary DNA damage measured by the comet assay was significantly higher in CKD patients than in controls. Among CKD patients, the following correlations were observed. (1) There was no difference in comet tail length or tail intensity between diabetic and non-diabetic individuals. (2) Age, sex, hemoglobin, hypertension, duration of hemodialysis, and ferritin levels affected neither tail length nor intensity. (3) BMI values above 25kg/m(2) and iPTH levels above 300pg/ml were associated with significantly greater comet tail length. Our results indicate that primary DNA damage is increased in CKD patients undergoing hemodialysis, compared to controls; however, DM had no additional effect.

Novel inflammatory marker in dialysis patients: YKL-40.

YKL-40 has been introduced as a marker of inflammation in different clinical situations. The association between YKL-40 and inflammation in chronic renal failure patients has not been researched currently. The objectives of this study were to establish serum YKL-40 concentrations in dialysis patients with chronic renal failure compared to healthy subjects and to explore its relationships with a proinflammatory cytokine, interleukine-6 (IL-6) and an acute phase mediator, high sensitivity C-reactive protein (hs-CRP). The study population included hemodialysis patients (N = 43; mean age of 40.9 ± 14.5), peritoneal dialysis patients (N = 38; mean age of 45.8 ± 13.7) and healthy subjects (N = 37; mean age of 45.5 ± 10.6). Serum concentrations of YKL-40, IL-6, hs-CRP and routine laboratory measures were evaluated. Compared to the healthy subjects, hemodialysis and peritoneal dialysis patients had higher concentrations of YKL-40, IL-6, hs-CRP, as well as lower concentrations of hemoglobin, serum albumin and high density lipoprotein-cholesterol (P < 0.001). YKL-40 concentrations were positively correlated with serum creatinine (P < 0.001, r = 0.495), IL-6 (P < 0.001, r = 0.306), hs-CRP (P = 0.001, r = 0.306) levels and inversely correlated with hemoglobin (P = 0.002, r = -0.285), serum albumin (P < 0.001, r = -0.355) and high density lipoprotein-cholesterol (P = 0.001, r = -0.306). In multivariate regression analysis YKL-40 was associated with creatinine, serum albumin and hs-CRP concentrations after adjustments with covariates. Dialysis patients with chronic renal failure have elevated serum YKL-40 concentrations. Associations with standard inflammatory parameters suggest that YKL-40 might be a novel inflammatory marker in this population.

The relationship between vascular endothelial growth factor (VEGF) and microalbuminuria in patients with essential hypertension.

OBJECTIVE: The existence of microalbuminuria (MAU) in patients with essential hypertension is a strong indicator of microvascular damage. Although endothelial dysfunction and increased vascular permeability both have a role in the development of MAU, its ethiopathogenesis in hypertensive patients is not yet clearly understood. Vascular endothelial growth factor (VEGF) is the most important regulator of pathological or physiological angiogenesis and it additionally leads to increased vascular permeability. This study aims to assess the relationship of serum VEGF levels to MAU in non-complicated, newly-diagnosed essential hypertensive patients (EHs). METHODS: This study included 30 newly-diagnosed EHs with MAU, 46 newly-diagnosed EHs without MAU and 46 healthy controls. None of the EHs had diabetes, renal impairment or atherosclerotic diseases. Serum VEGF levels were measured using the ELISA method. RESULTS: Serum levels of VEGF were significantly higher in EHs with MAU when compared with patients without MAU (225.15+/-109.34 pg/mL versus 166.78+/-114.35 pg/mL, p: 0.04) or controls (225.15+/-109.34 pg/mL versus 144.91+/-96.60 pg/mL, p: 0.007). On the other hand, no significant difference was observed between the non-MAU and control groups. In the univariate analysis, serum levels of VEGF, were positively correlated with systolic blood pressure (R: 0.253 p: 0.001), diastolic blood pressure (R: 0.162 p: 0.04), mean arterial pressure (R: 0.239 p: 0.002), creatinine clearance (R: 0.172 p: 0.04) and MAU (R: 0.338 p: 0.002). In the multiple linear regression analysis, VEGF levels were independently related to MAU (beta: 0.248, p: 0.02). CONCLUSION: VEGF levels are higher in EHs in the presence of MAU. These high values may be important in the early diagnosis of vascular damage in EHs. Additionally, VEGF may increase glomerular permeability and lead to MAU in EHs.