Ramipril and Cardiovascular Outcomes in Patients on Maintenance Hemodialysis: The ARCADIA Multicenter Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Renin-angiotensin system (RAS) inhibitors reduce cardiovascular morbidity and mortality in patients with CKD. We evaluated the cardioprotective effects of the angiotensin-converting enzyme inhibitor ramipril in patients on maintenance hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this phase 3, prospective, randomized, open-label, blinded end point, parallel, multicenter trial, we recruited patients on maintenance hemodialysis with hypertension and/or left ventricular hypertrophy from 28 Italian centers. Between July 2009 and February 2014, 140 participants were randomized to ramipril (1.25-10 mg/d) and 129 participants were allocated to non-RAS inhibition therapy, both titrated up to the maximally tolerated dose to achieve predefined target BP values. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the single components of the primary end point, new-onset or recurrence of atrial fibrillation, hospitalizations for symptomatic fluid overload, thrombosis or stenosis of the arteriovenous fistula, and changes in cardiac mass index. All outcomes were evaluated up to 42 months after randomization. RESULTS: At comparable BP control, 23 participants on ramipril (16%) and 24 on non-RAS inhibitor therapy (19%) reached the primary composite end point (hazard ratio, 0.93; 95% confidence interval, 0.52 to 1.64; P=0.80). Ramipril reduced cardiac mass index at 1 year of follow-up (between-group difference in change from baseline: -16.3 g/m2; 95% confidence interval, -29.4 to -3.1), but did not significantly affect the other secondary outcomes. Hypotensive episodes were more frequent in participants allocated to ramipril than controls (41% versus 12%). Twenty participants on ramipril and nine controls developed cancer, including six gastrointestinal malignancies on ramipril (four were fatal), compared with none in controls. CONCLUSIONS: Ramipril did not reduce the risk of major cardiovascular events in patients on maintenance hemodialysis. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ARCADIA, NCT00985322 and European Union Drug Regulating Authorities Clinical Trials Database number 2008-003529-17.

[Uremic Toxins: how can we improve the removal today?] / Tossine uremiche: come migliorarne la rimozione oggi.

Uremic status results from a malfunctioning of kidneys due to the accumulation of compounds which, under normal conditions, are excreted or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. Such compounds have toxic effects on the cardio-vascular system. An useful classification, published by the European Uremic Toxin Work Group (EUTox) is: 1) small water-soluble compounds; 2) protein-bound compounds; 3) the larger "middle molecules". High-flux membranes and more efficient treatment techniques, like HDF, improve the removal of uremic toxins in the middle molecular-weight range, and recent studies suggest that these strategies have better results on the morbidity and mortality. Today new membranes, medium cut-off membranes (MCO), with increased pore size, allow for the removal of higher molecular-weight toxins, such as kappa and lambda light chains and/or mediators of inflammation. For toxins in the 15 to 45 KD-size range, MCO membranes improve the removal in comparison with high-flux HD and/or HDF. Therefore MCO membrane simplifies the treatment of HD patients with a removal spectrum that extend the current possibilities of the best available therapies for End Stage Renal Disease.

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.