Background and objectives Few randomized controlled trials have compared intravenous iron products head to head in CKD patients with iron deficiency anemia. This study compared the efficacy and safety of two intravenous iron products (ferumoxytol [Feraheme injection] and iron sucrose [Venofer]) in patients with CKD and iron deficiency anemia.Design, setting, participants, & measurements In this phase II, randomized, open-label, active-controlled, multicenter clinical trial, patients were randomized 1:1 to either 1.02 g ferumoxytol (23510-mg injections) or 1.0 g iron sucrose administered as either a slow injection or infusion (10 doses for dialysis patients and 5 doses for nondialysis patients). Inclusion criteria included hemoglobin,11.0 g/dl, transferrin saturation,30%, and eGFR,60 ml/min per 1.73 m 2 or a diagnosis of underlying CKD (e.g., nephropathy or nephritis). The primary end point was change in hemoglobin from baseline to week 5. ResultsIn total, 162 patients were randomized. Demographics were balanced between the treatment groups. Adverse event profiles of the two regimens were fairly similar: overall adverse events, 48% ferumoxytol versus 65% iron sucrose; related adverse events, 10% ferumoxytol versus 16% iron sucrose; and adverse events leading to study discontinuation, 1% ferumoxytol versus 5% iron sucrose. Rates of serious adverse events and related serious adverse events were similar between the ferumoxytol and iron sucrose groups: serious adverse events, 9% versus 7%, respectively and related serious adverse events, 1% versus 1%, respectively. Overall, increases in hemoglobin were similar between treatment groups. Based on an ANOVA model adjusted for baseline hemoglobin level and dialysis status, the least squares mean change from baseline to week 5 was 0.860.1 g/dl in the ferumoxytol-treated group and 0.760.1 g/dl in the iron sucrose group. The difference in the mean change from baseline between the two treatment groups was 0.1 g/dl (95% confidence interval, 20.2 to 0.4). ConclusionIn this randomized, controlled trial, ferumoxytol and iron sucrose showed comparable efficacy and adverse events rates.

Background and objectives The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older ($65 years, n=1005) and younger (,65 years, n=2878) patients.Design, setting, participants, & measurements Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified.Results Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were .3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. ConclusionsIn the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.

Background and objectives Hemodialysis (HD) per se entails vascular dysfunction in patients with ESRD. Endothelial dysfunction is a key step in atherosclerosis and is characterized by impaired flow-mediated dilation (FMD). Interventional studies have shown that cocoa flavanol (CF)-rich supplements improve vascular function. Aim of this study was to investigate the effect of flavanol-rich bioactive food ingredients on acute and chronic HD-induced vascular dysfunction in ESRD.Design, setting, participants, & measurements We conducted a randomized, double-blind, placebo-controlled trial from 2012 to 2013. Fifty-seven participants were enrolled, ingested CF-rich beverages (900 mg CF per study day), and were compared with those ingesting CF-free placebo. This included (1) a baseline cross-over acute study to determine safety and efficacy of CF and (2) a subsequent chronic parallel group study with a 30-day follow-up period to study effects of CF on HD-mediated vascular dysfunction entailing (3) an acute substudy during HD in flavanol-naive patients and (4) an acute on chronic study during HD. Primary and secondary outcome measures included changes in FMD and hemodynamics.Results CF ingestion was well tolerated. Acute ingestion improved FMD by 53% (3.260.6% to 4.860.9% versus placebo, 3.260.7% to 3.360.8%; P,0.001), with no effects on BP or heart rate. A 30-day ingestion of CF led to an increase in baseline FMD by 18% (3.460.9% to 3.960.8% versus placebo, 3.560.7% to 3.560.7%; P,0.001), with reduced diastolic BP (73612 to 69611 mmHg versus placebo, 70611 to 73613 mmHg; P=0.03) and increased heart rate (70612 to 74613 bpm versus placebo, 75615 to 74613 bpm; P=0.01). No effects were observed for placebo. Acute ingestion of CF during HD alleviated HD-induced vascular dysfunction (3.460.9% to 2.760.6% versus placebo, 3.560.7% to 2.060.6%; P,0.001). This effect was sustained throughout the study (acute on chronic, 3.960.9% to 3.060.7% versus placebo, 3.560.7% to 2.260.6; P=0.01).Conclusions Dietary CF ingestion mitigates acute HD-induced and chronic endothelial dysfunction in patients with ESRD and thus, improves vascular function in this high-risk population. Larger clinical trials are warranted to test whether this translates into an improved cardiovascular prognosis in patients with ESRD.

In this single-arm, open-label, multicentre study, conversion of a large population of haemodialysis patients from epoetin or darbepoetin to monthly C.E.R.A. administration using pre-filled syringes was shown to be practical, convenient and offer good control of haemoglobin levels, regardless of the previous type of therapy or dosing frequency.

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