Determination of oxidative stress and cellular inflammation in patients with diabetic nephropathy and non-diabetic nephropathy being administered hemodialysis treatment due to chronic renal failure

Objectives: We aimed to evaluate oxidative stress [8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA)] endothelial damage [asymmetric dimethylarginine (ADMA)] and markers of cellular inflammation [interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), neopterin (NP) and high-sensitivity C-reactive protein (hsCRP)] in patients with diabetic nephropathy (DN) and non-diabetic nephropathy who were being administered hemodialysis treatment because of chronic renal failure. Methods: In determining 8-OHdG, IL-6 and TNF-α levels, Enzyme-Linked Immuno-Sorbent Assay method was used. Serum MDA, ADMA and NP levels were determined by using high performance liquid chromatography (HPLC). And hs-CRP values were measured with nephelometric method. Results: Serum 8-OHdG and MDA levels were found statistically to have increased when compared with those of the control group in patients groups after dialysis. However, serum ADMA and neopterin levels were observed statistically to have decreased when compared with those of the control group in patients groups after dialysis. But, decreases on ADMA and neopterin levels are still much higher than those of control. IL-6 and TNF-α levels were found to have increased when compared with those of control group in patients groups before dialysis. Conclusion: The oxidative stress in patients with DN, who were being treated with hemodialysis due to chronic renal failure, was higher than that of non-DN patients who were being treated with hemodialysis. In contrast with this, inflammation occurring in non-DN patients was found to have been higher than that of in patients with DN.     

Serum Leptin,Resistin, and Lipid Levels in Patients with End Stage Renal Failure with Regard to Dialysis Modality

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. Methods. This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) α levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. Results. Serum resistin, adiponectin, IL-6, TNF-α, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. Conclusion. Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.     

Changes in the inflammatory markers with advancing stages of diabetic nephropathy and the role of pentraxin-3

Background: Immunological and inflammatory mechanisms have been shown to have role in both the development and progression of diabetic nephropathy (DNP). There is need for more specific markers for inflammation as the ones commonly used are influenced by many factors. Pentraxin-3 (PTX-3) seems to be a potential candidate. We aimed in our study to evaluate the changes of PTX-3 levels in different stages of DNP and its relationship with other inflammatory markers.

Methods: This is a cross sectional study in which patients with DNP at different stages were involved. Patient were divided into three groups according to estimated glomerular filtration rate (eGFR), microalbuminuria and proteinuria levels: Group-1: eGFR >60?mL/min and microalbuminuria, Group-2: eGFR >60?mL/min and macroalbuminuria, Group-3: eGFR <60?mL/min and macroalbuminuria. Besides the routine biochemical parameters, levels of PTX-3, high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1 and tumor necrosis factor (TNF)-α was measured. Groups were compared with each other regarding the study parameters and correlation of PTX-3 with other markers was evaluated.

Results: The mean PTX-3 level in Group-2 (0.94?±?0.26?ng/mL) and -3 (1.35?±?1.55?ng/mL) were higher than in Group-1 (0.81?±?0.25?ng/mL) (p?=?0.009 and p?=?0.012). There was a significant correlation of PTX-3 with proteinuria (r?=?0.266, p?=?0.016), microalbuminuria (r?=?0.304, p?=?0.014) and hypoalbuminemia (r?=?0.197, p?=?0.043). PTX-3 was not correlated with other markers of inflammation (IL-1, TNF-α and hsCRP) and diabetic metabolic parameters (hbA1c, C-peptide, insulin and HOMA-IR). PTX-3, IL-1 and TNF-α levels increased with the advancing stage of DNP while hsCRP level did not change.

Conclusion: PTX-3 that increases similar to other markers of inflammation (IL-1, TNF-α) is a better inflammatory marker than hsCRP. Furthermore, there is a relationship between PTX-3 and proteinuria independent from eGFR.     

Serum leptin, resistin, and lipid levels in patients with end stage renal failure with regard to dialysis modality

Little information is available on the relationship between serum resistin levels and other adipokines with serum lipid levels and insulin resistance in uremic patients under different dialysis modalities. METHODS: This study investigated the effects of dialysis modality on serum leptin, adiponectin, resistin, interleukin 6 (IL-6), and tumor necrosis factor (TNF) alpha levels in age, sex, and total adipose tissue mass (TATM); matched 30 hemodialysis (HD) patients, 30 continuous peritoneal dialysis (CAPD) patients, and 30 healthy controls; and evaluated the relationship between these adipokines and dyslipidemia and insulin resistance. RESULTS: Serum resistin, adiponectin, IL-6, TNF-alpha, and high sensitive C reactive protein (hsCRP) levels were significantly increased in dialysis patients compared to controls (p < 0.05). In CAPD patients, serum leptin, resistin, triglycerides, and total cholesterol levels were higher than those in HD patients (p < 0.05). Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and low density lipoprotein (LDLc) levels in both dialysis groups. Resistin levels were found to positively correlate with TATM and triglycerides in CAPD patients. No relationship was found between the homeostasis model assessment-insulin resistance index (HOMA-IR) and adipokines studied. CONCLUSION: Serum leptin, resistin, triglycerides, and total cholesterol levels were higher in CAPD patients. Leptin levels were positively correlated with TATM, serum triglycerides, total cholesterol, and LDLc levels in dialysis patients. Resistin levels were positively correlated with TATM and triglycerides in CAPD patients. Glucose load during CAPD may be an important factor in increased in leptin, resistin, triglycerides, and total cholesterol levels in CAPD patients. These results highlight the importance of leptin and resistin as determinants of dyslipidemia, especially in CAPD patients.     

An Association Between Inflammatory State and Left Ventricular Hypertrophy in Hemodialysis Patients

This study was performed to investigate the potential relationship between left ventricular hypertrophy (LVH) and proinflammatory cytokines in hemodialysis (HD) patients and the effect of HD on cytokine production. Serum interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) measurements and echocardiographic studies were performed in 35 stable HD patients. A variety of probable risk factors for LVH including age, HD duration, blood pressure (BP), body mass index, lipid profile, hemoglobin, albumin, parathormone and homocysteine levels were also investigated. Additionally, the effect of HD procedure on cytokine levels was evaluated. Predialysis serum levels of IL-1β, IL-6, TNF-α, and homocysteine in HD patients were compared with 12 healthy subjects. Left ventricular hypertrophy was demonstrated in 20 (57%) of HD patients by echocardiography. Left ventricular mass index (LVMI) was correlated positively with systolic BP (r = 0.556, p = 0.001), diastolic BP (r = 0.474, p = 0.004), and serum levels of TNF-α (r = 0.446, p = 0.009).Multiple regression analysis showed that systolic BP and TNF-α levels were significant independent predictors of LVH. No relationship was observed between LVH and other parameters. The mean predialysis serum level of IL-6 was significantly higher in HD patients compared to healthy controls (15.7 ± 8.7 vs. 7.3 ± 0.7 pg/mL, p = 0.001). Predialysis serum levels of TNF-α in HD patients were higher when compared to healthy subjects, but the difference was not statistically significant (8.3 ± 3 vs. 7 ± 1.45 pg/mL, respectively, p > 0.05). However, serum levels of IL-6 and TNF-α significantly elevated after HD, when compared to predialysis levels (from 15.7 ± 8.7 to 17.8 ± 9.5 pg/mL, p = 0.001 and from 8.3 ± 3.0 to 9.9 ± 3.5 pg/mL p = 0.004, respectively). As a conclusion, in addition to BP, proinflammatory cytokines, TNF-α in particular, seem to be associated with LVH in ESRD patients.     

虫草制剂联合复方α酮酸对腹膜透析患者微炎症状态的影响

目的探讨虫草制剂联合复方α酮酸治疗对维持性腹膜透析患者全身微炎症状态的影响。方法选择江苏省沭阳县人民医院肾内科和黑龙江省佳木斯大学附属第一临床医学院肾内科确诊慢性肾衰竭尿毒症期并行持续非卧床腹膜透析（continuous ambulatory peritoneal dialysis,CAPD）治疗1个月以上的患者46例,随机分成对照组和治疗组,每组23例。对照组行CAPD治疗（CAPD治疗方案为：患者使用由美国百特公司生产的1．5％及2．5％腹膜透析液2L／袋,白天用1．5％腹膜透析液3袋,每袋留腹4h,夜间使用2．5％腹膜透析液1袋保留过夜约10h,第2天清晨放出）治疗;治疗组在CAPD治疗的同时给予虫草制剂与复方α酮酸口服,分别于治疗前及治疗后第3个月采用乳胶凝集反应法检测患者血清超敏C反应蛋白（hypersensitive C reaction protein,hs-CRP）、采用（enzyme-linked immunosorhent assay,ELISA）法测定肿瘤坏死因子a（tumornecrosisfactoralpha-α,TNF-α）和白细胞介素6（interleukin6,IL-6）水平,并比较2组之间的差异。结果治疗组治疗后第3个月时hs-CRP和IL-6较治疗前显著降低,差异有统计学意义（P〈0．05）。与对照组比较,对照组患者存在全身微炎症状态,血清hs-CRP、TNF-α、IL-6水平明显高于治疗组,差异有统计学意义（P〈0．05）。结论虫草制剂与复方α酮酸联合应用能减轻维持性腹膜透析患者的全身微炎症状态。     

Effects of intradialytic exercise on systemic cytokine in patients with chronic kidney disease

Abstract

Background: Immunological dysfunctions and a pro-inflammatory environment are associated with higher risk of cardiovascular diseases in chronic kidney disease (CKD). Physical exercise can be an important anti-inflammatory strategy, but the effects in CKD remain poorly investigated. Objective: Evaluate the acute inflammatory response to intradialytic exercise in the peripheral blood of individuals with CKD. Methods: Nine patients, of both genders, with CKD and allocated in the ambulatory of hemodialysis of Hospital Ernesto Dornelles (Brazil), performed two sessions of hemodialysis (HD) in random form: aerobic intradialytic exercise sessions (EX, 20?min of moderate exercise in cycle-ergometer) and a control hemodialysis session (CON). Peripheral blood collection was made at the baseline, during and immediately after HD to evaluate the cytokine profile: interleukin-6, interleukin-10 (IL-10), interleukin-17a (IL-17a), interferon-gamma (INF-γ) and tumoral necrosis factor-alpha (TNF-α). Results: INF-γ decreased during HD when compared with the pre moment in both sessions, while an increase in post HD was only found in the CON session. IL-17 was higher in post when compared with during HD in both sessions. In addition to the time effect, IL-10 presented a time?×?group interaction and the relative changes were significantly higher in EX when compared with the CON session. The relative changes in TNF-α tended to be higher in CON when compared with EX immediately post HD session. Conclusions: These data indicate that 20?min of intradialytic exercise have modest effect in systemic inflammation. However, the significant increase in IL-10 may indicate an immunoregulatory effect of physical exercise.     

Preclinical efficacy of Dexmedetomidine on spinal cord injury provoked oxidative renal damage

Abstract

Purpose: Oxidative renal injury is the mainstay in patients with spinal cord injury (SCI) and it may eventuate to chronic renal failure. In our study, we investigated the potential of α2-adrenoreceptor agonist Dexmedetomidine (Dex) in ameliorating SCI provoked oxidative renal assault. Methods: Complete SCI was generated by surgical transaction of the cord at the T10–12 level. Dex administration (50?mcg/kg, b.wt, intraperitoneally) was initiated 12?h after the surgery for 10 days. Then, blood was collected and kidneys were removed to evaluate the efficacy of Dex on post-SCI renal complications. Results: Dex treatment significantly attenuated elevated serum creatinine and blood urea nitrogen in SCI rats to normalcy. Further in SCI rats elevated level of MDA, protein carbonyl and myeloperoxidase (MPO) were observed and Dex treatment significantly attenuated these toxic manifestations to normalcy. Besides in SCI rats, the antioxidants (SOD, CAT, Gpx and GST and GSH) levels were significantly diminished and Dex treated rats significantly restored the antioxidants level in renal tissue to normalcy. Notably, in our study the protein expression of inflammatory cytokines (TNF-α and IL-6) and cleaved caspase-3 were upregulated in renal tissue of SCI rats. Fascinatingly, Dex treatment downregulated the protein expression of TNF-α, IL-6 and cleaved caspase-3 by anti-inflammatory, antiapoptotic mechanism. Furthermore, SCI rats displayed upregulated protein expression of kidney of SCI rats. Dex treatment diminished the renal apoptosis by downregulating the cleaved caspase-3 expression. Conclusion: Taken together, these results accentuate that Dex may be a beneficial clinical agent to combat post-SCI renal complications.     

The Relationship of Visfatin Levels to Inflammatory Cytokines and Left Ventricular Hypertrophy in Hemodialysis and Continuous Ambulatory Peritoneal Dialysis Patients

Visfatin was recently defined as an adipocytokine; however, the pathophysiological role of visfatin is not completely understood. A few studies suggest that visfatin may be a new proinflammatory adipocytokine. The aim of the present study was to compare serum visfatin levels between hemodialysis and continuous ambulatory peritoneal dialysis (CAPD) patients and evaluate the relationship between visfatin levels to IL-6, TNF-α, and left ventricular hypertrophy. Serum visfatin, IL-6, and TNF-α levels were measured by using the ELISA method, and echocardiographic evaluations were performed in 31 hemodialysis patients, 30 CAPD patients, and 21 healthy volunteers. Serum visfatin levels were higher in the CAPD group (265.27 ± 387.86 ng/mL) than hemodialysis (97.68 ± 244.96 ng/mL,) and control (41.33 ± 48.87 ng/mL) groups (p = 0.04, p = 0.01, respectively). No significant difference was observed between the hemodialysis and control groups. In univariate analysis, visfatin levels were positively correlated with IL-6 (r = 0.24, p = 0.03), TNF-α (r = 0.34, p = 0.002), and BMI (r = 0.26, p = 0.03) and negatively correlated with some left ventricular diastolic parameters [Em and Em/Am (r = ?0.305, p = 0.01), (r = ?0.251, p = 0.03), respectively]. No relationship was found between visfatin and left ventricular mass index. In the linear regression analysis, visfatin levels independently related with TNF-( (β = 0.369, p = 0.001) and IL-6 (β = 0.284, p = 0.015). This study has found significantly higher levels of serum visfatin in CAPD patients when compared to healthy individuals. Increased visfatin levels seem to associate with proinflammatory cytokines such as IL-6 or TNF-α. As for the effects of on left ventricular structure and functions, visfatin might have negative effects on left ventricular diastolic function parameters but have no effects on left ventricular mass index.     

The odontogenic-related microinflammation in patients with chronic kidney disease

Objectives: This study estimated plasma levels of interleukin IL-1β, IL-6, tumour necrosis factor-α (TNF-α), interferon-γ (INF-γ) in chronic kidney disease (CKD) patients with a single odontogenic pathology. Material and methods: Forty-nine selected adult CKD patients with single odontogenic pathology based on clinical and X-ray examination: patients after proper root canal treatment, without periapical lesions (n?=?12), with pulp necrosis (n?=?7), with asymptomatic periapical lesions (n?=?22), with periodontal disease (n?=?8), and 14 with healthy teeth were enrolled. Patients with coexisting different dental pathologies and the evidence of other infection were excluded. In all patients plasma concentrations of CRP, IL-1β, IL-6, TNF-α, and INF-γ were measured. Results: Patients with periodontitis were characterized by increased concentrations of IL-6 and TNF-α. Those with pulp necrosis had significantly more frequently serum CRP level over 2?mg/L and presented significantly elevated IL-6, but decreased TNF-α concentration than in the subjects with healthy teeth. In patients with periapical lesions and patients after root canal therapy, the concentrations of cytokines did not indicate for the systemic inflammation. Conclusions: Periodontitis and pulp necrosis are important sources of systemic microinflammation in CKD patients. Plasma concentrations of IL-6 and TNF-α appear to be more sensitive markers of odontogenic inflammation in CKD patients than CRP.     

不同血液净化方式对尿毒症透析患者血中细胞因子清除的临床应用

目的 研究不同血液净化方式对尿毒症透析患者血中细胞因子的清除效果.方法 将2006年4月至2009年2月在我院血液净化中心透析的45例患者按随机数字表法分为(1)血液透析联合血液灌流组;(2)血液透析滤过组;(3)HD组,血液透析组,每组15例.血液透析联合血液灌流组、血液透析滤过组每周治疗1次,每组患者治疗3次,中间间隔1周,第1次及第3次治疗前、后各从动脉端采血5 ml,并留取正常健康对照组血液,整批送检.测定治疗前、后血清细胞因子的浓度.结果 血液灌流联合血液透析组、血液透析滤过组及血液透析组治疗前、后白细胞介素1β、白细胞介素6、肿瘤坏死因子α浓度与健康对照组比较差异有统计学意义(P＜0.01);血液透析组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(3±10)ng/L、(4±9)ng/L、(4±9)ng/L,治疗前、后差值比较分别为176.0%、141.0%、187.0%,血液透析滤过组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(39±15)ng/L、(36±14)ng/L、(45±16)ng/L,治疗前后差值比较分别为24.6%、22.1%、29.8%,血液灌流联合血液透析组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(48±16)ng/L、(38±15)ng/L、(50±14)ng/L,治疗前差值比较分别为27.8%、23.9%、32.3%,3组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平间比较差异有统计学意义(t分别=17.39、11.24、21.89,P均＜0.01).结论 不同的血液净化方式对各类细胞因子的清除效果不同,其中液灌流联合血液透析组及血液透析滤过组治疗埘细胞因子清除有效,血液透析组治疗对细胞因子清除基本无效,液灌流联合血液透析组及血液透析滤过组细胞因子清除效果与血液透析滤过组比较差异无统计学意义(P＞0.05).     

Association of serum IL-18 with protein-energy wasting in end-stage renal disease patients on haemodialysis

Purpose

Protein-energy wasting (PEW) is highly prevalent in end-stage renal disease (ESRD) patients with inflammation who are on haemodialysis treatment. Interleukin-18 (IL-18) is an important pro-inflammatory cytokine that is significantly elevated in ESRD patients. However, the relationship between PEW and IL-18 is unclear. We therefore performed a cross-sectional study on 100 ESRD patients undergoing haemodialysis to clarify this.

Methods

PEW was defined according to the diagnostic criteria of the International Society of Renal Nutrition and Metabolism. Inflammation was assessed based on the serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α) and IL-18. We analysed the association between PEW and IL-18 by using logistic analysis and linear regression after adjustment for basic characteristics, comorbidities and laboratory findings.

Results

Among the 100 haemodialysis patients who were recruited, 56 had PEW. Even though there was no difference between the PEW group and non-PEW group with regard to disease causes, age, gender, cholesterol, ferritin, and haemoglobin, the levels of inflammation indicators such as CRP, IL-6, TNF-α and IL-1β were significantly higher in the PEW group. Moreover, IL-18 was found to contribute to PEW, but was negatively correlated with pre-albumin after adjustment for possible confounding factors.

Conclusions

Thus, the findings indicate that IL-18 is associated with PEW in ESRD patients on haemodialysis, which suggests that IL-18 may be involved in the pathogenesis of PEW in this setting.

     

The Effect of Renal Replacement Therapies on Serum Gastrointestinal System Hormones

Background. The kidney is a major site for the inactivation, degradation, and clearance of a variety of peptide hormones. It has been shown that the uremia increases or decreases gastrointestinal system (GIS) hormones. Moreover, studies investigating the serum GIS hormones levels in chronic renal failure (CRF) were conducted mainly in a particular period of the renal replacement therapy, and the changes caused by continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis (HD) could not be fully demonstrated. In this study, we investigated the effect of CAPD and HD on serum GIS hormones (amylase, lipase, trypsinogen, and gastrin) levels in CRF patients who were diagnosed for the first time. Methods. Serum amylase, lipase, trypsinogen, and gastrin levels were measured in 36 patients who were just diagnosed with CRF, 22 patients with CAPD and 14 patients with HD. GIS hormones of these patients were measured before treatment and three months from the beginning of CAPD and HD treatment. As the control group, 20 normal healthy cases with well-matched age and gender were used. Results. The mean serum amylase, lipase, secretin, and gastrin levels were found meaningfully decreased according to the beginning values at third months of the CAPD and HD treatment. However, they were higher than control group. Conclusion. In patients receiving CAPD or HD as renal replacement therapy, GIS hormone levels were found to be lower, albeit higher than the healthy control group.     

Reduction of Pro-Inflammatory Cytokines through Hemodiafiltration

Background. Hemodialysis (HD) prolongs the life of the patients with end stage renal disease (ESRD), but the survival rates are still lower than the general population. More than half of ESRD patients died from cardiovascular disease (CVD). Recent studies have revealed that CVD is a consequence of vascular inflammation, and that there are active inflammatory processes in ESRD patients. Reports have indicated that ESRD patients have fewer CVD events and better survival with hemodiafiltration (HDF), but the reasons for this remain unclear. This study attempts to prove that HDF reduces the CVD-related cytokines. Methods. Seventeen adult HD outpatients were put on HDF in our hospital from September 2004 to June 2006. We collected plasma samples before and six months after initiation of HDF. The target pro-inflammatory cytokines selected were interleukin-6 (IL-6), interleukin-18 (IL-18), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Results. After six months of HDF, most of the biochemical parameters did not changed. Plasma IL-18 and TNF-α are decreased significantly (p?<?0.05) but IL-6 and CRP are not. Conclusions. IL-18 and INF-α decreased significantly after six months of HDF. These cytokines are key factors in atherosclerotic plaque formation and rupture, and a reduction of these inflammatory cytokines in HDF may reduce the CVD incidence and prolong life.     

The Evaluation of Effects of Demographic Features,Biochemical Parameters,and Cytokines on Clinical Outcomes in Patients with Acute Renal Failure

Aim. To evaluate the effects of cytokines, biochemical parameters and demographic features on clinical outcomes of acute renal failure (ARF). Patients and Methods. 59 patients with acute renal failure (28 men, 31 women) were enrolled to the study. Cytokines, biochemical parameters, and complete blood count were measured. Patients were divided into two groups: as survivors (group 1, n = 46) and nonsurvivors (group 2, n = 13). Results. Mean age of patients were 52.3 ± 17.9 years. 46 patients survived (77.9%) and 13 patients died (22.1%). There was a statistically significant relationship between IL-2R, IL-6, and TNF-α levels and mortality rates (p = 0.004, p = 0.016, p = 0.020, respectively) and between TC levels and mortality rates (p = 0.041). In multivariable logistic regression analysis, the effects of proinflammatory cytokines (IL-1β, IL-2R, IL-6, TNFα, CRP, and ESR) on the clinical outcomes in ARF was observed to be statistically significant (r = 0.341, p = 0.005). Conclusion. We realized that in totally demographic features (male gender, advanced age, poor nutritional status), biochemical parameters (TC, albumin, and hemoglobin) and cytokine levels (IL-2R, IL-6, TNF-α), CRP and ESR may be predictive factors for mortality in patients with ARF.     

Plasma ghrelin and leptin in adult cystic fibrosis patients

BackgroundWeight loss in cystic fibrosis (CF) may be associated with altered levels of appetite stimulating peptide ghrelin and the appetite decreasing peptide leptin. However, prior data on leptin in CF are conflicting, while the data on ghrelin are scarce. We hypothesized that weight loss in CF is associated with low levels ghrelin and elevated levels of leptin.MethodsPlasma ghrelin, leptin, TNF-α, IL-1 and IL-6, BMI, fat free mass (FFM), fat mass (FM) were measured in 74 CF adults and 20 controls. CF subjects were divided into 3 groups based on lung disease: mild (n = 19), moderate (n = 30) and severe (n = 25).ResultsSevere CF patients (% predicted FEV1 27 ± 7; median BMI 21 kg/m²) had significantly elevated ghrelin and decreased leptin compared to controls and other CF subjects. Ghrelin correlated (r value, p value) with BMI (− 0.35,< 0.001), FFM (− 0.22,< 0.05), FM (− 0.41,< 0.0001), FEV1 (− 0.62,< 0.001), TNF-α (0.51,< 0.0001), IL-1 (0.56,< 0.0001), and IL-6 (0.33,< 0.01). Leptin correlated (r value, p value) with BMI (0.40,< 0.0001), FM (0.56,< 0.0001), FEV1 (0.34,< 0.05), IL-1 (− 0.51,< 0.05) and TNF-α (− 0.43,< 0.0001). BMI and FEV1 were independent predictors of ghrelin (− 0.35,< 0.05;−0.59,< 0.001). FM was a predictor of leptin (0.56,< 0.0001). Cytokines were elevated only in severe CF (severe CF vs. controls, pg/ml): TNF-α (3.4 ± 0.6 vs. 1.2 ± 0.4), IL-1 (3.5 ± 1 vs. 0.2 ± 0.1), IL-6 (17.4 ± 4 vs. 2.4 ± 2).ConclusionsElevated ghrelin and decreased leptin levels are a consequence rather than a cause of weight loss in advanced CF.     

Effects of melatonin on the serum levels of pro-inflammatory cytokines and tissue injury after renal ischemia reperfusion in rats

Abstract

We investigated the changes in the serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6, the pro-inflammatory cytokines, and the possible effect of melatonin on the modulation of these inflammatory molecules after renal ischemia reperfusion (IR). The study was carried out in the laboratory of Department of Pharmacology. Forty-six male Wistar albino rats were divided into five groups as control (n?=?6), positive control (n?=?4), sham (n?=?12), renal IR (n?=?12), and renal IR melatonin (n?=?12). After 1?h renal pedicle occlusion, the blood samples were taken for the measurement of cytokine levels at second hour of the reperfusion. The rats were sacrificed after 24?h of reperfusion for histopathological evaluation. Melatonin or vehicle was administrated to IR rats. Lipopolysaccharide (LPS) was administered to the positive control group and the blood was taken at fourth hour. Serum TNF-α levels increased significantly in renal IR and LPS groups. Serum IL-6 levels were not different from control except the LPS group. There was no significant correlation between the serum TNF-α levels and the histopathological score after renal IR. Melatonin treatment reversed the increase of serum TNF-α levels and histopathological injury in renal tissue after renal IR. Melatonin may have a protective effect by reducing the serum level of TNF-α in renal IR.     

Inflammation and oxidation: do they improve after kidney transplantation? Relationship with mortality after transplantation

Summary

Patients with chronic kidney disease (CKD) are characterized by a state of inflammation and oxidative stress that seems to improve after kidney transplantation (KT). Nevertheless, there is controversy regarding what is the best marker that better define inflammation and specially oxidative stress.

Objective

To evaluate the biomarkers which are associated with improvements in inflammation and lipid peroxidation in patients who have undergone KT. To evaluate the relationship between inflammation, lipid peroxidation and mortality in KT.

Patients

196 KT (between 2003 and 2008). 67.9% men; median age: 51.9 years. Inflammation markers analyzed previous KT and 3 months after KT: c-reactive protein(CRP), interleukin 6(IL-6), tumor necrosis factor alpha(TNFα), soluble tumor necrosis factor receptor alpha(sTNFRα), soluble interleukin-2 receptor (sIL-2R). Lipid peroxidation markers analyzed: oxidized low-density lipoprotein (oxLDL) and anti-oxLDL antibodies. Calculation of glomerular filtration rate after KT: MDRD equation.

Results

Following KT, there is a significant decrease in CRP (p = 0.006), IL-6 (p = 0.0037), TNFα (p < 0.0001), sTNFRα (p < 0.0001) and sIL-2R (p < 0.0001), while levels of oxLDL increase after KT (p < 0.0001) and there is not a significantly difference in anti-oxLDL. 12.8% of the patients had died in 2012. These patients had higher levels of IL-6 (p = 0.011) and sTNFRα (p < 0.006) after KT and a lower MDRD (p < 0.0001), hemoglobin (p = 0.012) and albumin (p = 0.007). We observed no statistically differences in the levels of markers previous KT. Of the patients who died, the 43.5% of them had anti-oxLDL antibody levels greater than 75th percentile (P₇₅: 3781 UI/ml, p = 0.028). In the multivariate analysis, age (OR:1.12; p = 0.0129), MDRD (OR:0.92; p = 0.013) and P₇₅ of anti-oxLDL(OR: 5.19; p = 0.026) were independent risk factors for mortality. Independent risk factors for survival were: P₇₅ of IL-6 (HR: 2.45; p = 0.027), oxLDL (HR:19.85; p = 0.002) and anti-oxLDL (HR: 9.55; p = 0.003).

Conclusions

KT improved inflammation but not lipid oxidative state. KT patients who died had a higher inflammatory state (with higher levels of IL-6 and sTNFRα), a worse lipid oxidative state and a worse renal function 3 months after KT. Age, anti-oxLDL and renal function at 3 months after KT were independent risk factors for mortality.

     

Study of the role of tumor necrosis factor-α (–308 G/A) and interleukin-10 (–1082 G/A) polymorphisms as potential risk factors to acute kidney injury in patients with severe sepsis using high-resolution melting curve analysis

Rational: Septic acute kidney injury (AKI) is a prevalent complication in intensive care units with an increased incidence of complications.

Objective: The aim of the present study was to assess the use of high-resolution melting curve (HRM) analysis in investigating whether the genetic polymorphisms; –308?G/A of tumor necrosis factor-α (TNF-α), and –1082?G?/A of Interleukin-10 (IL-10) genes may predispose patients diagnosed with severe sepsis to the development of AKI.

Methods: One hundred and fifty patients with severe sepsis participated in the present study; only sixty-six developed AKI. Both polymorphisms were studied using HRM analysis.

Main findings: The low producer genotype of both studied polymorphism of TNF-α and IL-10 genes was associated with AKI. Using logistic regression analysis, the low producer genotypes remained an independent risk factor for AKI. A statistically significant difference was detected between both studied groups as regards the low producer genotype in both TNF-α?(–308?G/A) and interleukin-10 (IL-10) (–1082?G/A) polymorphisms being prevalent in patients developing AKI.

Principle conclusions: The low producer genotypes of both TNF-α (–308?G/A) and IL-10 (–1082?G/A) polymorphisms could be considered a risk factor for the development of AKI in critically ill patients with severe sepsis, thus management technique implemented for this category should be modulated rescuing this sector of patients from the grave deterioration to acute kidney injury. Using HRM for genotyping proved to be a highly efficient, simple, cost-effective genotyping technique that is most appropriate for the routine study of large-scale samples.     

Leptin in CAPD patients: serum concentrations and peritoneal loss.

BACKGROUND: To determine whether serum leptin concentrations in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) are influenced by peritoneal loss of leptin and to compare serum leptin levels of normal subjects with those of patients receiving renal replacement therapy such as haemodialysis (HD), CAPD, or kidney transplantation. SUBJECTS AND METHODS: Eighty-four individuals were investigated: six females and 14 males on standard CAPD; 13 females and 13 males on chronic HD; 10 female and eight male kidney transplant recipients, and 10 female and 10 male subjects as controls. Morning serum, 8-h and 24-h samples of peritoneal fluid concentrated to 6-20-fold by Centricon 3 (cutoff 3000 daltons), and 24-h urinary concentrations of leptin were measured with commercial RIA (Linco Research, Inc., USA). Venous blood and peritoneal fluid samples of albumin, beta2-microglobulin, glucose, urea, and creatinine were determined by standard laboratory techniques. Serum insulin levels were measured by radioimmunoassay. RESULTS: Patients (men and women) on CAPD and after kidney transplantation exhibited significantly higher serum concentrations of leptin and leptin/BMI ratios than control subjects. These increased values did not reach statistical significance in HD patients. Serum leptin concentrations were correlated very significantly with BMI in all cases (r=0.380, P<0.001). Moreover, in CAPD patients (r=0.630, P<0.007) and in HD patients (r=0.668, P<0.005), but not in kidney transplant recipients or control subjects, significant correlations were observed between serum leptin and insulin concentrations. Residual renal function (RRF) in the range 0-12.8 ml/min and serum beta2-microglobulin levels in the range 7.9-47.1 mg/l did not influence serum leptin levels in CAPD and HD patients. As expected, leptin was detected in the peritoneal fluid of CAPD patients. Twenty-four-hour peritoneal loss (30.95+/-21.05 ng/min) and 24-h peritoneal clearance (0.01+/-0.01 ml/kg/min) of leptin account for only 3.9% of estimated whole-body leptin production rate and 0.7% of leptin clearance from plasma respectively. Twenty-four-hour urinary losses of leptin in CAPD patients were negligible, accounting for 5.6+/-1.8% (range 0.3-15.2%) of total (peritoneal and urinary) loss of this hormone. CONCLUSIONS: These findings suggest that serum leptin levels are not affected by continuous peritoneal loss of leptin during CAPD and that insulin resistance and hyperinsulinaemia contribute to elevated serum leptin concentrations in CAPD and HD patients. The aetiology of increased serum leptin levels in kidney transplant recipients is probably different from that in dialysis patients.