[New oral anticoagulants (NOAC) in nephrology]. / I nuovi Anti-Coagulanti Orali (NOAC): cosa deve sapere un Nefrologo.

The new or direct oral anticoagulants [new oral anticoagulants (NOAC) or direct oral anticoagulants (DOAC)] were launched in the Italian market in 2013. Although these compounds share common pharmacological indications with vitamin K antagonists (warfarin or acenocumarol), they have different mechanisms of action, do not require a constant anticoagulant monitoring but are more efficacious and safer than vitamin K antagonists. The use of these molecules (Dabigatran, Apixaban, Rivaroxaban, Betrixaban, Edoxaban) is constantly rising in daily practice. However, while available data suggest that NOAC/DOAC use is safe, dosage should be adjusted based on renal or liver function. It should be acknowledged that commonly available blood tests [Prothrombin Time (PT) and partial thromboplastin time (PTT)] are not indicated to monitor the anticoagulant activity of these compounds. With the exception of dabigatran, we currently lack of an antidote to reverse the anticoagulant effect of NOAC/DOAC. We herein review available evidence on NOAC/DOAC pharmacokinetic, risk factors for bleeding, interventions to reverse the anticoagulant activity in case of hemorrhages or need of urgent surgery and/or NOAC/DOAC overdose or side effects.

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.

The middle-arm fistula as a valuable surgical approach in patients with end-stage renal disease.

BACKGROUND: American and European guidelines recommend the distal radial-cephalic fistula (dRCF) as the first and best hemodialysis access in patients with end-stage renal disease (ESRD). However, this kind of arteriovenous fistula (AVF) shows a limited primary unassisted patency and frequently needs surgical revisions or angiographic procedures, or both. When dRCF is not feasible, guidelines suggest a proximal brachiocephalic AVF. The middle-arm fistula (MAF), or autogenous forearm radial-median direct access, has been suggested as a possible alternative approach. This study evaluated MAF primary unassisted patency, the most frequent causes of MAF failure, and the possible related factors. METHODS: Data on patients with a MAF placed from January 1991 until June 2008 were retrospectively collected. The probability of MAF failure overall and by the main subgroups was estimated according to Kaplan-Meier with Greenwood standard error (SE). Comparison of failure among different subgroups was performed using the log rank test in univariate analyses. The Cox regression model was used to investigate factors that independently affected the overall hazard of failure and cause-specific hazard of thrombosis. RESULTS: At the end of follow-up, 14.0% of MAF failed (11.6% thrombosis, 1.7% stenosis, 0.7% failed maturation), and 44.2% of MAF were still working. Cumulative probability of MAF unassisted primary patency after 4 years from the creation was 79%. Univariate analyses highlighted that women (P = .019), underweight patients (P = .010), and MAF implantation after starting hemodialysis (P < .001) had a higher risk of MAF failure for any cause than men, normal and overweight patients, and MAF implanted before starting hemodialysis. Results of the Cox multivariate analysis for overall MAF failure confirmed that only MAF implantation before starting hemodialysis is a protective factor against any failure (P = .003), whereas female gender (P = .016) was associated with an increase of the thrombosis hazard ratio to 2.04 (95% confidence interval, 1.14-3.63). CONCLUSION: Our data demonstrate that MAF has a good unassisted primary patency and suggest that this kind of AVF could be a valuable alternative surgical approach when dRCF is not feasible in ESRD patients.

Validation of QB stress test as a useful tool in the detection of native arteriovenous fistula stenosis: results after 22 months of follow-up.

BACKGROUND: Access flow (QA) surveillance is the best method recommended for early stenosis detection, but in native arteriovenous fistula (AVF), the literature is conflicting about the real need for monthly monitoring of QA, as suggested by the K-DOQI Guidelines. METHODS: From 1 January 2006 to 31 October 2007 (mean 18.0 +/- 4.9 months), we prospectively followed up 224 patients with monthly AVF monitoring by means of clinical examination and QB stress test (QBST). Suspected malfunctioning AVFs were referred to ultrasound dilution technique (UDT) and imaging techniques (Doppler ultrasonography, angiography), with eventually further percutaneous angioplasty (PTA) or surgical revision. RESULTS: We observed a good correlation between QBST and QA measurement obtained by the UDT. Patients with positive QBST had a lower QA than negative QBST subjects (433 +/- 203 vs 1168 +/- 681 ml/min, P < 0.0001). Fifty-four out of 224 (24%) patients were selected for possibly malfunctioning AVF. We found no stenosis in 13 out of 54 (24%) patients, inflow stenosis in 29 out of 54 (54%) patients and outflow stenosis in 12 out of 54 (22%) patients. The QBST positive predictive value for inflow stenosis was 76.3%. The interventional radiologist performed 38 PTA procedures in 33 patients (11 PTA per 100 patient-years) and we surgically created 13 new AVF (3.7 per 100 patient-years). Only five thrombosis episodes occurred in five patients during the follow-up (1.5 thromboses per 100 patient-years). CONCLUSIONS: QBST is a simple, low-cost, not time-consuming test, able to select, together with clinical evaluation, malfunctioning AVF with stenosis located specifically in the inflow tract. Our follow-up data demonstrated that it is possible to achieve a low AVF thrombosis rate by adding QBST in an AVF monitoring program, thus reducing the surveillance burden.

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.