Timing of nephrology referral and initiation of dialysis as predictors for survival in hemodialysis patients: 5-year follow-up analysis.

BACKGROUND: A consensus about the optimal timing of dialysis initiation is still controversial. Thus, the goal of this analysis was to compare outcomes in patients with early and late referral with early and late initiation of hemodialysis (HD). METHODS: We studied 190 patients (mean age 52.03±14.22) who were initiated on HD between 1994 and 2004. Patients who received regular nephrology care during 12 months before HD initiation were categorized as early referrals (ER) and those without nephrology care were late referrals (LR). The early start (E-start) was defined by the estimated GFR (eGFR) at start of HD≥7.5 mL/min/1.73 m2, and the late start (L-start) by eGFR of <7.5 mL/min/1.73 m2. The four groups of patients (ER with E-start and L-start; LR with E-start and L-start) were prospectively followed in the next 60 months after HD initiation. RESULTS: During the follow-up, 43.3% of E-start and 43.2% of L-start patients died, without significant difference in survival between the groups [HR for L-start vs. E-start=1.06 (95% CI 0.69-1.62); p=0.797]. When survival between ER and LR groups was compared (28.1% patients in the ER and 53.2% in the LR died), there was significant difference in survival [HR for LR vs. ER=2.16 (95% CI 1.28-3.65); p=0.004]. Compared with patients with ER and L-start, higher mortality was observed among those with LR and L-start [HR 3.51 (95% CI 1.48-8.35); p=0.004] and LR with E-start [HR 2.79 (95% CI 1.16-6.7); p=0.022]. There was no significant difference between patients in ER with L-start and ER with E-start. CONCLUSIONS: Our study showed that ER above 12 months before HD initiation and L-start of dialysis was associated with a reduced mortality risk in HD patients.

Increase in skin autofluorescence and release of heart-type fatty acid binding protein in plasma predicts mortality of hemodialysis patients.

Advanced glycation end-products (AGEs) are uremic toxins that accumulate progressively in hemodialysis (HD) patients. The aim of this study was to assess the 1-year increase in skin autofluorescence (ΔAF), a measure of AGEs accumulation and plasma markers, as predictors of mortality in HD patients. One hundred sixty-nine HD patients were enrolled in this study. Skin autofluorescence was measured twice, 1 year apart using an AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands). Besides routine blood chemistry, additional plasma markers including superoxide dismutase, myeloperoxydase, intercellular adhesion molecule 1 (ICAM-1), C-reactive protein (hs-CRP), heart-type fatty acid binding protein (H-FABP), and von Willebrand factor were measured at baseline. The mortality of HD patients was followed for 36 months. Skin autofluorescence values of the HD patients at the two time points were significantly higher (P < 0.001) than those of healthy subjects of the same age. Mean 1-year ΔAF of HD patients was 0.16 ± 0.06, which was around seven- to ninefold higher than 1-year ΔAF in healthy subjects. Multivariate Cox regression showed that age, hypertension, 1-year ΔAF, hs-CRP, ICAM-1, and H-FABP were independent predictors of overall mortality. Hypertension, 1-year ΔAF, hs-CRP, and H-FABP were also independent predictors of cardiovascular mortality. One-year ΔAF and plasma H-FABP, used separately and in combination, are strong predictors of overall and cardiovascular mortality in HD patients.

Does hepatitis C increase the accumulation of advanced glycation end products in haemodialysis patients?

BACKGROUND: Hepatitis C may cause increased levels of oxidative stress that contribute to accumulation of advanced glycation end products (AGEs), which increase the risk of cardiovascular disease (CVD). The aim of this study was to determine the influence of hepatitis C on AGE accumulation in haemodialysis patients. METHODS: AGE accumulation was measured by means of skin autofluorescence (AF) in 92 haemodialysis (HD) patients and 93 age-matched healthy controls. In the HD patients, CVD-related biochemical variables were also measured. The HD patients were tested for hepatitis C virus (HCV) antibodies and allocated to a HCV+ or HCV- group. RESULTS: Skin AF of the healthy subjects was lower than skin AF in the HD patients (3.13 +/- 0.95 vs 2.2 +/- 0.47; P < 0.001). We calculated the average increase of skin AF in the healthy subjects to be 0.017 arbitrary units per year, being 14 times lower than in HD patients with CVD only and 20 times lower than in HD patients suffering from combined CVD and diabetes mellitus (DM). Multivariate regression analysis showed that AGE accumulation in HD patients can be described by the independent effects of age, DM, CVD and HD vintage. Although inter-cellular adhesion molecule 1 and liver enzymes were elevated in HCV+ HD patients, levels of oxidative stress markers and skin AF were not significantly different between HCV+ and HCV- HD patients. CONCLUSIONS: AGE accumulation was higher in the HD patients than in the healthy controls. AGE accumulation did not differ in HCV+ and HCV- HD patients. This might be due to the fact that hepatitis C did not cause oxidative stress in our HD population. Independent markers of AGE accumulation were age, HD vintage, DM and CVD, but not hepatitis C.

Long-term follow up of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients.

PURPOSE: The aim of this study was to evaluate the persistence of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients. METHODS: 14 hemodialysis patients with chronic hepatitis C were treated with pegylated interferon alpha-2a for a period of 48 weeks. Achieved sustained viral response rate was 35.7% (5/14 patients) at week 72, i.e. 24 weeks after the treatment ended. All treated patients were then prospectively followed until week 144. Follow-up viral data, such as HCV antibodies, serum HCV RNA, and HCV RNA genotype, were determined at week 96 and week 144. HCV antibodies were determined by a 3rd-generation ELISA assay. The presence of HCV RNA was determined using reverse transcriptase polymerase chain reaction (AMPLICOR Hepatitis C Virus Test). HCV genotype was analyzed by reverse transcriptase polymerase chain reaction followed by hybridization of amplified products. The biochemical data were recorded every 24 weeks during the follow-up period. RESULTS: The 5 patients (35.7%), who achieved sustained viral response (SVR), remained HCV RNA negative at week 96. At week 144, 4 hemodialysis patients (28.6%) remained HCV RNA negative. There was a relapse of HCV infection in 1 patient after week 96 of the study. The patients who remained HCV RNA negative also maintained the achieved biochemical response throughout the follow-up period. CONCLUSION: Long-term follow-up of treated hemodialysis patients with pegylated interferon alpha-2a showed persistence of the sustained viral and biochemical response.

Treatment of hepatitis C in hemodialysis patients with pegylated interferon alpha-2a as monotherapy.

BACKGROUND: The high prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is of great concern because they have a higher rate of mortality than HCV-negative hemodialysis patients. The aim of the study was to evaluate the efficacy and safety of pegylated interferon alpha-2a monotherapy in hemodialysis patients with chronic HCV infection. METHODS: Fourteen dialysis patients with chronic HCV infection were scheduled to receive 135 mug pegylated interferon alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. Efficacy and safety were assessed by end of treatment viral response, sustained viral response, biochemical response, and adverse events. Serum HCV RNA levels were assessed using reverse transcriptase polymerase chain reaction (RT-PCR), while HCV genotype was analyzed by RT-PCR followed by hybridization of amplified products. RESULTS: Of the 14 patients enrolled in the study, 9 completed treatment. Eight patients (57%) had undetectable levels of HCV RNA at the end of treatment, while one patient remained positive. Two (14.3%) patients were discontinued because of insufficient therapeutic response. Three patients (21.34%) did not finish treatment because serious adverse events occurred: one patient with bronchopneumonia and one with pericarditis were discontinued from treatment, while one patient died due to cerebral hemorrhage. Sustained viral response was present in 36% of the patients (5/8 patients) at the end of the follow up period. Biochemical response with normalization of serum ALT levels during treatment was observed in all treated patients (83 +/- 20.1 U/L at baseline vs. 23.4 +/- 4.6 U/L at week 48). The most common adverse events were flu-like syndrome, myalgia, arthralgia, and pancytopenia. Most of the adverse events were manageable. The serious adverse events were believed to be unrelated to the therapy, but rather to the co-morbidities of the hemodialysis patients. CONCLUSIONS: Pegylated interferon alpha-2a treatment was effective in a considerable proportion of the treated hemodialysis patients with hepatitis C, and it was reasonably safe to use.