Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans

Background Arteriosclerosis obliterans (ASO) in hemodialysis patients is the dominant cause of morbidity evolving from arteriosclerosis. Adiponectin is an adipose-derived cytokine which, because of its modulation of endothelial adhesion molecules, has potential anti-inflammatory and anti-atherogenic properties. However, the implications of adiponectin and endothelial function in ASO of hemodialysis patients has not been fully elucidated. Methods In this study we measured serum levels of adiponectin, adhesion molecules (VCAM-1 and ICAM-1), and an endothelial cell injury marker (CD146) in patients with ASO. We sought to determine clinical and laboratory correlates of ASO in ESRD patients. A total of 80 hemodialysis patients and 82 patients with normal serum creatinine levels were enrolled. Serum levels of adiponectin, ICAM-1, VCAM-1, and CD146 were measured by ELISA. Results Serum adiponectin levels in 41 hemodialysis patients with ASO were significantly lower than in 39 patients without ASO. Serum CD146 levels in hemodialysis patients with ASO were significantly higher than in patients without ASO. There were no significant differences between levels of ICAM-1 and VCAM-1 in these two groups. Similar results were obtained for patients with normal renal function. Serum adiponectin was related to hemodialysis duration and BMI in hemodialysis patients. In patients with normal renal function, adiponectin was related to HDL-cholesterol, triglyceride, and ICAM-1. Conclusion A decrease in serum adiponectin levels and an increase in serum CD146 may be closely associated with the development of ASO, regardless of renal function. However, there are different mechanisms determining serum adiponectin levels in patients with normal kidney function and in hemodialysis patients. In memory of Dr Kenji Okuda (1944–2007).     

Reduction of left ventricular hypertrophy in children undergoing hemodialysis

Left ventricular hypertrophy (LVH) is related to a 1,000-fold increased risk of cardiovascular morbidity and mortality in young adults with end-stage renal disease (ESRD) treated with hemodialysis (HD) or peritoneal dialysis. We report a series of 17 children (5 girls, 12 boys), with a median (range) age of 11 (2–18) years, all treated by HD, who presented with an increased left ventricular mass (LVM) index of 54.8±4.5 g/m^2.7 at onset of HD and reached 36.2±2.6 g/m^2.7 (mean±SEM, P<0.0001) at last follow up. Over the observation period, systolic (P<0.0001) and diastolic (P<0.0001) blood pressure (indexed for height, gender, and age) decreased and hemoglobin (+2.8 g/dL; P<0.0001) increased compared to initial values. Only BP as well as plasma protein level at onset of HD session correlated with LVM in multiple correlation analysis. In conclusion, increased LVM is a common feature in pediatric patients with ESRD. Normalization of BP and reduction of the extracellular volume (represented by plasma protein at onset of HD session) are key points in reducing LVH during HD in children.     

Long-term outcome of chronic dialysis in children

We describe the outcome since 1984 of all children receiving chronic dialysis in our centre for >3 months with a minimum follow-up of 5 (median 7.2) years. There were 98 children (61 boys), with a median age at the start of dialysis of 4.2 (range: birth to 16.2) years. Twenty-one children started dialysis at <1 year of age and 54 under <5 years. Thirty children had significant comorbidity. The median time on dialysis was 1.4 (0.3 to 14.4) years, giving a total dialysis experience of 296 patient-years. Fifty-three children received a renal transplant as their first change of treatment modality, but 31 switched between PD and HD, with a total of 54 changes of dialysis modality pre-transplantation. Twenty-one of the transplanted patients (39%) returned to dialysis. There were a total of 115 transplants in 88 patients. There was a positive increase for both the weight and height SDS for all the age groups while on dialysis, but this did not reach statistical significance. There were 17 deaths over the 20-year study period; of these, 10 died on dialysis. The overall patient survival was 83%. The mortality rate was 2.7 times greater in children who required renal replacement therapy under the age of 5 years. Of the deaths, 76% were in association with comorbid conditions. In conclusion, both a younger age at the start of renal replacement therapy and comorbidity are significant risk factors for death. The number of returnees to dialysis highlights the importance of conserving dialysis access.     

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome was retrospectively studied in 78 children in eight centers for the past 20 years. Median age at onset was 4.4 years (1.1–15.0 years) and the gender ratio was 1.4. Median follow-up period was 7.7 years (1.0–19.7 years). The disease in 45 patients (58%) was initially not steroid-responsive and in 33 (42%) it was later non-responsive. The main therapeutic strategies included administration of ciclosporine (CsA) alone (n = 29; 37%) and CsA + mycophenolate mofetil (n = 18; 23%). Actuarial patient survival rate after 15 years was 97%. Renal survival rate after 5 years, 10 years and 15 years was 75%, 58% and 53%, respectively. An age at onset of nephrotic syndrome (NS) > 10 years was the only independent predictor of end-stage renal disease (ESRD) in a multivariate analysis using a Cox regression model (P < 0.001). Twenty patients (26%) received transplants; ten showed recurrence of the NS: seven within 2 days, one within 2 weeks, and two within 3–5 months. Seven patients lost their grafts, four from recurrence. Owing to better management, kidney survival in idiopathic steroid-resistant nephrotic syndrome (SRNS) has improved during the past 20 years. Further prospective controlled trials will delineate the potential benefit of new immunosuppressive treatment.     

Renal transplantation and chronic dialysis in children and adolescents: the 1993 annual report of the North American Pediatric Renal Transplant Cooperative Study

The 1993 North American Pediatric Renal Transplant Cooperative Study annual report summarizes data voluntarily contributed by 82 participating centers on 3,223 pediatric patients who received 2,819 renal transplants from January 1987 through January 1993 and 999 independent courses of dialysis from January 1992 through January 1993. In addition to updating information regarding trends and outcomes in pediatric renal transplantation presented in previous annual reports, 1st-year registry data are presented regarding current practices and trends in chronic dialysis therapy for children and adolescents in North America. Living donor graft (LDG) survival rate was 90% at 1 years 85% at 2 years and 75% at 5 years post transplant. Cadaver graft (CG) survival rates were 76%, 71% and 62% at 1, 2 and 5 years post transplant, respectively. Overall mortality post transplantation continues to be low (CG 6.8%, LDG 4%), mortality remains high in young infants. The dialysis cohort was generally younger than the transplantation cohort. In all age groups, peritoneal dialysis was utilized in the majority of pediatric patients and the overall incidence of peritonitis was 1 episode per 8.2 patient months. External percutaneous catheters were utilized as the predominant chronic hemodialysis access in the study, and access site infections ranged from 6.9% at 1 month to 13.5% at 6 months.Center     

碳酸镧与传统磷结合剂治疗维持性血液透析患者高磷血症的Meta分析

目的 评价碳酸镧与传统磷结合剂治疗维持性血液透析患者高磷血症的疗效和安全性.方法 计算机检索MEDLINE(1996-2012.12)、EBCO (1996-2012.12)、Cochrane图书馆临床对照试验资料库和中文万方数据库(1996-2012.12).手工检索已发表或未发表的相关文献,包括会议摘要等.检索无语种限制.纳入碳酸镧与传统磷结合剂比较治疗维持性血液透析患者高磷血症的随机对照试验.由两名评价员独立评价纳入研究的质量和提取资料,并用RevMan 5.0软件进行Meta分析.结果 共纳入10项研究.Meta分析结果显示,碳酸镧与传统磷结合剂相比,降低血磷水平的疗效差异无统计学意义[WMD=-0.06,95％ CI(-0.27～0.15),P=0.57],但碳酸镧治疗组血钙水平低于含钙磷结合剂,两组间因不良反应退出情况差异无统计学意义,碳酸镧治疗组高钙血症发生率低于传统磷结合剂.结论 碳酸镧治疗对终末期肾脏疾病维持性血液透析患者高磷血症有效,且其高钙血症发生率低于传统磷结合剂.     

DAA‐based antiviral treatment of patients with chronic hepatitis C in the pre‐ and postkidney transplantation setting

DAA‐based regimens for chronic hepatitis C infection encourage treatment of “difficult‐to‐treat” cohorts. This study investigated efficacy and safety of DAA‐based regimens in HCV patients on dialysis or postkidney or liver/kidney transplantation. Twenty‐five patients treated with DAA combinations were evaluated: 10 were on dialysis (eight: hemodialysis, two: peritoneal dialysis), eight were kidney transplant recipients, and seven were liver/kidney transplant recipients. Except for one patient treated with daclatasvir ([DCV]/60 mg/QD)/simeprevir ([SMV]/150 mg/QD), the others received sofosbuvir‐based regimens ([SOF];400 mg/QD) combined with SMV:eight, DCV:13 or either ledipasvir ([LDV]90 mg/QD), ribavirin ([RBV];weight based) or pegylated interferon/RBV. HCV‐RNA was determined by Abbott RealTime (LLOQ]:12 IU/ml) or Roche AmpliPrep/COBAS TaqMan assay (LLOQ:15 IU/ml); treatment response evaluated every 4 weeks, at the end of treatment, and 4 and 12 weeks thereafter. Twenty‐four (96%) patients achieved SVR 12/24 (ITT‐analysis). Mean treatment duration was 15.1 ± 5.1 weeks (±SD), and two patients terminated prematurely – both reached SVR12. Six patients were hospitalized due to complications of underlying disease. One patient achieved SVR24 but was re‐infected (week 27). Kidney function remained stable; serum creatinine increased in only one patient – SOF was reduced to 400 mg/48 h. Treatment with DAA combinations in renally impaired HCV patients is highly effective and well tolerated. These findings call for further controlled trials and data from real‐life cohorts.     

Independent validation of stromal uPA in ABCSG-08: Level 1b evidence for the prognostic value of uPA immunohistochemistry

PurposeTo validate the prognostic role of urokinase-type plasminogen-activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) protein expression in FFPE archived tumor samples when assessed by immunohistochemistry.Patients and methodsFresh-frozen, paraffin-embedded (FFPE) samples from 303 postmenopausal women with hormone receptor-positive, early breast cancer were investigated. The patients had received 5 years of endocrine therapy in the prospectively randomized ABCSG-8 trial. Immunohistochemistry for stromal uPA and PAI-1 protein expression was correlated with distant recurrence-free survival (DRFS) and overall survival (OS).ResultsWe detected stromal uPA in 132 of 297 tumors (44.4%) and stromal PAI-1 expression in 74 out of 299 samples (24.7%). Co-expression of uPA and PAI-1 was present in 48 of 294 (16.3%) cases. Neither uPA nor PAI-1 expression was associated with tumor size, age, nodal status, grading, or quantitative receptor status. Patients whose tumor stroma expressed uPA protein had a significantly shorter DRFS (adjusted HR for relapse: 2.78; 95% CI 1.31–5.93; p = 0.008 Cox regression analysis) than women without uPA expression. No such association was seen for PAI-1 and the uPA/PAI1 ratio. After a median follow-up of 5.6 years, women with uPA-positive tumors demonstrated significantly shorter DRFS (93.3% vs. 84.8%; p < 0.013 log-rank test), and tended to have a worse OS (83.0% vs. 77.3%; p = 0.106) compared to women with uPA negative tumors.ConclusionThis independent validation in archived tumor samples from a large prospective randomized trial confirms the clinical utility of stromal uPA evaluation by immunohistochemistry. This provides level 1b evidence for the prognostic role of stromal uPA in women with endocrine-responsive early breast cancer.     

Novel Risk Factors for Progression of Diabetic and Nondiabetic CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

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