Serum concentrations of free indoxyl and p-cresyl sulfate are associated with mineral metabolism variables and cardiovascular risk in hemodialysis patients.

BACKGROUND: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are uremic toxins associated with cardiovascular outcome in CKD patients. The present work is an analysis of the association of serum free, total IS and PCS with cardiovascular events and calcium-phosphate metabolism variables in hemodialysis patients. METHODS: Serum levels of total and free IS and PCS were measured in 139 hemodialysis patients. Their relationship with calcium-phosphate metabolism variables were tested in an observational cohort study. In addition, their association with cardiovascular events was investigated during a 4-year follow-up. RESULTS: Patients in the highest tertile (T3) of serum free IS showed lower serum 1,25(OH)2D compared to patients in the middle (T2) and lowest tertile (T1); in addition to this, T3 patients showed lower serum irisin than T1 patients and lower serum PTH than all the other subjects (T1 + T2) combined. Serum PTH was also measured during the two years after the baseline measurement and was higher in patients in the T1 than in those in the T3 of serum free IS. Cox regression analysis showed that cardiovascular risk was lower in T1 patients than in those in the T3 of serum free PCS, both using a univariate (OR 2.55, 95% CI 1.2-5.43; p = 0.015) or multivariate model (OR 2.48, 95% CI 1.12-5.51; p = 0.003). CONCLUSIONS: Serum free IS may be associated with PTH and 1,25(OH)2D secretion, whereas free PCS may predict cardiovascular risk in hemodialysis patients.

Kinetics of Hepatitis B virus load during haemodialysis sessions and α-interferon: a prospective study.

BACKGROUND: It has been reported a slow progression of hepatitis B in patients undergoing maintenance dialysis, and a role of dialysis session per se has been suggested. The aim of the present study is to evaluate the kinetics of the hepatitis B viral load (HBV DNA) in serum during haemodialysis sessions using a highly sensitive technique; the role of interferon-α in lowering HBV viral load in such patients was also investigated. METHODS: HBV DNA was determined in 24 HBsAg positive patients on maintenance hemodialysis immediately before and after a 4-hour hemodialysis session, the same measurements were repeated 48 and 72 hours later. HBV DNA quantitation was performed by a novel RealTime PCR assay. Serum IFN-α levels were tested in parallel in a subset of HD sessions (n=40) by ELISA. RESULTS: 20 (83%) HBsAg positive patients had detectable HBV DNA in serum. Positive status for HBV DNA in serum was not predicted by demographic, clinical or biochemical parameters. HBV load decreased in many patients after hemodialysis sessions 5.92 log10 IU/mL (95% CI, 5.34 to 6.28 log10 IU/mL) vs. 4.79 log10 IU/mL (95% CI, 4.23 to 6.15 log10 IU/mL) (P=0.02). A significant relationship between mean HBV DNA levels before dialysis and percentage reduction of HBV DNA during HD sessions occurred [F-test=5.41, rho (least squares)=0.307]. Increase of serum IFN-α levels was found in a minority (3/40=7%) of HD sessions. CONCLUSIONS: Hemodialysis procedure gives reduction of HBV load in HBsAg chronic carriers; no relationship with IFN-α activity during HD sessions was found. The kinetics of HBV viremia in HD procedures could explain the low viral load which is typically observed in these patients. Further studies to identify the mechanisms responsible for reduction of HBV viremia during HD procedures are under way.

Novel assay using total hepatitis C virus (HCV) core antigen quantification for diagnosis of HCV infection in dialysis patients.

Dialysis patients remain a high-risk group for hepatitis C virus (HCV) infection. The current diagnosis of HCV infection among dialysis patients includes serological assays and nucleic acid amplification technology (NAT) for assessing serum anti-HCV antibody and HCV viremia, respectively. However, current NAT techniques are expensive and labor-intensive and often lack standardization. An assay prototype designed to detect and quantify total HCV core antigen (total HCV core Ag) protein in serum and plasma in the presence or absence of anti-HCV antibodies has been recently developed. A comparison between a total anti-HCV core Ag enzyme-linked immunosorbent assay (ELISA) and a quantitative HCV RNA assay based on reverse transcription-PCR (RT-PCR) (Amplicor HCV Monitor test) was performed using a large (n = 305) cohort of ELISA HCV 3.0 HCV-negative and -positive patients on maintenance dialysis. The concentrations of HCV core Ag and HCV RNA levels (measured by RT-PCR) were significantly correlated (r = 0.471, P = 0.0001) over a wide range of HCV RNA levels and were maintained among different HCV genotypes (HCV genotype 1, r = 0.862, P = 0.0001; HCV genotype 2, r = 0.691, P = 0.0001). We estimated that 1 pg of total HCV core Ag per ml is equivalent to approximately 19.952 IU of HCV RNA per ml, even if the wide range in the ratio of core Ag to HCV RNA (95% confidence intervals, 2.8 x 10(3) to 1.6 x 10(5) IU/ml) precluded definitive conclusions. In summary, total HCV core Ag proved to be useful for performing HCV RNA measurement among dialysis patients in routine laboratories without the need for special equipment or training. The present study supports the use of the total anti-HCV core Ag ELISA for assessing viral load among dialysis patients with HCV infection.

Biological dynamics of hepatitis B virus load in dialysis population.

BACKGROUND: Control of the spread of hepatitis B virus (HBV) infection in dialysis units has been one of major advances in the management of end-stage renal disease. However, the natural history of HBV in dialysis patients remains unclear. The aim of this study is to measure monthly HBV viral load (HBV DNA) in a large cohort (n = 29) of hepatitis B surface antigen (HBsAg)-positive chronic dialysis patients during 12 months. METHODS: HBV DNA was measured using the Amplicor HBV Monitor Test (Roche Diagnostics, Branchburg, NJ), an in vitro assay using polymerase chain reaction nucleic acid amplification and DNA hybridization for the quantitative measurement of HBV DNA in serum. RESULTS: We observed three HBV DNA patterns: (1) patients persistently positive by Amplicor HBV Monitor Test (persistent HBV DNA; 7 of 29 patients; 24.1%), (2) individuals with alternatively positive and negative results (intermittent HBV DNA; 18 of 29 patients; 62.1%), and (3) patients persistently negative by Amplicor HBV Monitor Test (4 of 29 patients; 13.8%). HBV viral load was greater in patients with persistent compared with intermittent HBV DNA (persistently HBV DNA positive; 2.686 x 10(4) copies/mL; 95% confidence interval [CI], 5.2499 x 10(4) to 1.8158 x 10(4)copies/mL) versus intermittently HBV DNA positive (1.071 x 10(3) copies/mL; 95% CI, 8.524 x 10(3) to 4.09 x 10(2) copies/mL; P = 0.0001). In the entire group, HBV load at study entry was low and did not change versus the end of follow-up. CONCLUSION: Three patterns of HBV viremia in dialysis patients over time were assessed; HBV load was not high and was relatively stable. HBsAg-positive patients who were intermittently HBV DNA positive had less HBV viral load than persistently HBV DNA-positive patients. Periodic testing for HBV DNA to assess the virological status of HBsAg-positive dialysis patients is recommended.

Epidemiology of GB virus c/hepatitis g virus infection in patients on peritoneal dialysis.

BACKGROUND: A new genus in the family Flaviviridae has recently been discovered; it has provisionally been designated GBV-C/HGV. As determined by virologic techniques [reverse-transcription polymerase chain reaction (RT-PCR)], infection with GBV-C/HGV is frequent in renal transplant (RT) recipients and in patients on chronic hemodialysis (HD). The epidemiology of GBV-C/HGV infection in patients on peritoneal dialysis is scarce and mostly based on RT-PCR technology. PURPOSE: We report on the prevalence (as detected by serologic and virologic techniques) and the risk factors for GBV-C/HGV infection in a cohort of patients on continuous ambulatory peritoneal dialysis (CAPD). We also tested a control group of blood donors. METHODS: Infection by GBV-C/HGV was assessed by serologic and virologic techniques. Cases of GBV-C/HGV viremia (GBV-C/HGV RNA) were detected by RT-PCR. Antibodies to the envelope protein of GBV-C/HGV (anti-E2 GBV-C/HGV antibody) were analyzed by serologic methods. RESULTS: We found a high frequency [17/85 (20%)] of GBV-C/HGV. The rates of GBV-C/HGV viremia and anti-E2 GBV-C/HGV positivity were 10.5% (9/85) and 10.5% (9/85) respectively. In most patients [17/18 (94%)], the presence of anti-E2 GBV-C/HGV antibody was associated with clearance of GBV-C/HGV from serum. No relationship was noted between anti-E2 GBV-C/HGV antibody (or GBV-C/ HGV viremia) and age, sex, race, time on dialysis, anti-HCV antibody, HBsAg status, and anti-HIV positivity. The frequency of GBV-C/HGV infection in CAPD patients was much higher than that in blood donors, even if the difference did not approach statistical significance. No associations between GBV-C/HGV positivity and biochemical liver tests [aminotransferase and gamma glutamyl transpeptidase (GGT)] were apparent. CONCLUSIONS: Infection by GBV-C/HGV as detected by RT-PCR and anti-E2 antibody was common in patients on CAPD and in controls alike. No association was seen between GBV-C/HGV and various demographic or clinical factors. The clinical significance of GBV-C/HGV in CAPD remains unclear. Larger investigations are in progress.