Effects of oral vitamin C supplementation on oxidative stress and inflammation status in haemodialysis patients.

BACKGROUND: There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients. Limited data, however, are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients. METHODS: We ran a prospective, randomized, open-label trial to assess the effects of oral vitamin C supplementation (250 mg three times per week) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis (HD) patients. RESULTS: Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls, C-reactive protein and albumin, or erythrocyte concentrations of reduced and oxidized glutathione. CONCLUSION: Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients. Whether a higher oral dose or the intravenous route can modify these markers remains to be determined.

Increased pasma S-nitrosothiol concentrations predict cardiovascular outcomes among patients with end-stage renal disease: a prospective study.

The plasma concentrations of S-nitrosothiols, which are circulating nitric oxide metabolites with potential biologic activity, are increased among patients undergoing chronic hemodialysis (HD). However, the ability of S-nitrosothiols to release nitric oxide at physiologically relevant sites may be reduced among HD patients, because of impaired availability and/or activity of factors involved in S-nitrosothiol breakdown. The resultant lack of S-nitrosothiol bioavailability could contribute to the high cardiovascular risk for such patients. A possible relationship between plasma S-nitrosothiol levels and cardiac outcomes, as well as all-cause mortality rates, was investigated in a cohort of 250 chronic HD patients and who were undergoing regular dialysis three times per week were monitored for 1 yr. During that follow-up period, major cardiac events and all-cause deaths were prospectively recorded. At baseline, high plasma S-nitrosothiol levels (>2 micro M, corresponding to the top quartile of all measured values) were independently associated with pulse pressure in an adjusted multivariate analysis (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.05; P = 0.007). During the follow-up period, 36 patients died (16 as a result of cardiac causes) and 33 patients experienced major adverse cardiac events. In an adjusted Cox proportional-hazards model, high plasma S-nitrosothiol concentrations (i.e., the top quartile versus the three other quartiles) were an independent predictor of cardiac events (hazard ratio, 3.30; 95% confidence interval, 1.61 to 6.76; P = 0.001) but not of all-cause death. Therefore, among chronic HD patients, markedly elevated plasma S-nitrosothiol levels are associated with pulse pressure and predict cardiovascular outcomes. These findings support the hypothesis that impaired S-nitrosothiol bioavailability in uremia is an important factor for the excessive cardiovascular risk among HD patients.

Prognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study.

BACKGROUND: Cardiac disease is the main cause of mortality in long-term hemodialysis patients. Cardiac troponins (cTn) have been proposed to be markers of cardiac damage, but their value is still debated in hemodialysis patients. The aim of this prospective study is to assess the prognostic value of biochemical cardiac markers in long-term hemodialysis patients. METHODS: We measured serum levels of cTn I (cTnI), cTn T (cTnT), and creatine kinase-MB (CK-MB) in 258 asymptomatic patients (mean age, 60 +/- 15 years; 150 men) before the dialysis treatment. All causes of death and major adverse cardiac events (MACEs: cardiac death, myocardial infarction, or unstable angina) were recorded at 1 and 2 years of follow-up. A Cox proportional hazard regression model was used to identify factors predictive of mortality. RESULTS: On inclusion, 48 patients (18.6%) had cTnT levels greater than 0.1 ng/mL, 46 patients (17.8%) had cTnI levels greater than 0.15 ng/mL, and 18 patients (7.0%) had CK-MB levels greater than 3 ng/mL. Of 246 patients followed up at 2 years, 64 patients (26%) had died, including 29 patients (11.8%) of cardiac disease, and 49 patients (19.9%) experienced at least 1 MACE. MACEs were significantly greater for patients with elevated predialysis serum cTnT and CK-MB levels (>0.1 ng/mL and 3 ng/mL, respectively) than for patients with normal levels of these cardiac markers (31.9% versus 17.1%; P = 0.01; 38.9% versus 18.4%; P = 0.02, respectively). No differences were found for cTnI levels. In multivariate analysis, age (relative risk [RR], 1.04; P = 0.002), previous ischemic heart disease (RR, 2.5; P = 0.0001), and serum cTnT levels greater than 0.1 ng/mL (RR, 1.9; P = 0.04) were independent significant factors for MACEs. CONCLUSION: Increased predialysis serum levels of cTnT and CK-MB, but not cTnI, were predictive of a high risk for overall mortality and MACEs at 2 years in asymptomatic hemodialysis patients.

Mesenteric ischaemia in haemodialysis patients: a case/control study.

BACKGROUND: Mesenteric ischaemia is not uncommon in dialysis patients and seems to have been increasing in the last decade. However, the risk factors for mesenteric ischaemia are unclear and prognosis of patients after this type of ischaemic accident is not well defined. METHODS: From January 1988 to June 1999, 15 haemodialysis patients (0.3% per patient-year) from a single institution presented with mesenteric ischaemia and the clinical, biological and radiological aspects of the ischaemia were described. To identify risk factors for mesenteric ischaemia, each ischaemic patient (case) was matched with two other haemodialysis patients not having ischaemia (controls). Survival curves were then established for the two groups. RESULTS: A marked hypotensive episode was present in seven out of 15 case patients (47%) during dialysis sessions that preceded mesenteric ischaemia. Abdominal pain, guarding, fever and hyperleucocytosis were all present in 13 out of 15 patients (87%). An abdominal computerized tomography scan with opaque enema enabled a rapid diagnosis for six patients. The caecum was the most frequently (47%) affected segment. Twelve patients were surgically treated and the remaining three were given medical support. The two groups (case and control) were not different in cardiovascular risk factors, comorbidity, administered drugs or main haemodialysis characteristics. The median survival of the case group was 600 days, whereas 80% of the control group survived beyond this period (P=0.0132). Eleven case patients survived >3 months after mesenteric ischaemia and had a median survival of 1500 days, which was identical to their matched control patients. CONCLUSIONS: Mesenteric ischaemia should be systematically suspected in patients experiencing abdominal pain during or after dialysis sessions. Prompt diagnosis and treatment usually allow for a favourable prognosis.

Long-term results of a prospective randomized study comparing two immunosuppressive regimens, one with and one without CsA, in low-risk renal transplant recipients.

Due to the nephrotoxicity of cyclosporin A (CsA), its benefit on long-term graft survival remains controversial, especially in low-risk patients. Here we report the 12-year results of a calcineurin-inhibitor-free regimen. One hundred and seventeen low-risk kidney recipients were prospectively randomized to maintenance therapy with either a combination of azathioprine and prednisone (group NoCsA, n=58), or with cyclosporine, azathioprine, and prednisone (group CsA, n=59). Both groups received induction therapy with anti-lymphocyte globulins (ALG). Twelve-year patient survival was 75% and 82.5% in the CsA and NoCsA groups, respectively [ P= not significant (NS)]. Twelve-year graft survival was 59% and 56% ( P=NS) in the CsA and NoCsA groups, respectively (NS). Transplant rejection rates were similar in both groups. Mean serum creatinine levels after 10 years were 161 and 136 micromol/l in the CsA and NoCsA groups, respectively. Rejection-free patients of the CsA group had poorer renal function (168 micromol/l) than those of the NoCsA group (121 micromol/l; P=0.0060). We concluded that a 12-year graft survival of 56% and a graft half-life of 15 years can be achieved without the primary use of a calcineurin inhibitor in low-risk patients receiving ALG. Patients treated with CsA had poorer graft function at 12 years.

Outbreak of hepatitis C virus infection in a hemodialysis unit: potential transmission by the hemodialysis machine?

OBJECTIVE: To identify the routes of transmission during an outbreak of infection with hepatitis C virus (HCV) genotype 2a/2c in a hemodialysis unit. DESIGN: A matched case-control study was conducted to identify risk factors for HCV seroconversion. Direct observation and staff interviews were conducted to assess infection control practices. Molecular methods were used in a comparison of HCV infecting isolates from the case-patients and from patients infected with the 2a/2c genotype before admission to the unit. SETTING: A hemodialysis unit treating an average of 90 patients. PATIENTS: A case-patient was defined as a patient receiving hemodialysis with a seroconversion for HCV genotype 2a/2c between January 1994 and July 1997 who had received dialysis in the unit during the 3 months before the onset of disease. For each case-patient, 3 control-patients were randomly selected among all susceptible patients treated in the unit during the presumed contamination period of the case-patient. RESULTS: HCV seroconversion was associated with the number of hemodialysis sessions undergone on a machine shared with (odds ratio [OR] per additional session, 1.3; 95% confidence interval [CI95], 0.9 to 1.8) or in the same room as (OR per additional session, 1.1; CI95, 1.0 to 1.2) a patient who was anti-HCV (genotype 2a/2c) positive. We observed several breaches in infection control procedures. Wetting of transducer protectors in the external pressure tubing sets with patient blood reflux was observed, leading to a potential contamination by blood of the pressure-sensing port of the machine, which is not accessible to routine disinfection. The molecular analysis of HCV infecting isolates identified among the case-patients revealed two groups of identical isolates similar to those of two patients infected before admission to the unit. CONCLUSIONS: The results suggest patient-to-patient transmission of HCV by breaches in infection control practices and possible contamination of the machine. No additional cases have occurred since the reinforcement of infection control procedures and the use of a second transducer protector.