Kidney international
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Kidney international · Nov 2016
Randomized Controlled Trial Multicenter StudyVadadustat, a novel oral HIF stabilizer, provides effective anemia treatment in nondialysis-dependent chronic kidney disease.
Current treatment of anemia in chronic kidney disease (CKD) with erythropoiesis-stimulating agents can lead to substantial hemoglobin oscillations above target range and high levels of circulating erythropoietin. Vadadustat (AKB-6548), a novel, titratable, oral hypoxia-inducible factor prolyl hydroxylase inhibitor induces endogenous erythropoietin synthesis and enhances iron mobilization. In this 20-week, double-blind, randomized, placebo-controlled, phase 2b study, we evaluated the efficacy and safety of once-daily vadadustat in patients with stages 3a to 5 non-dialysis-dependent CKD. ⋯ Serious adverse events occurred in 23.9% and 15.3% of the vadadustat- and placebo-treated patients, respectively. Three deaths occurred in the vadadustat arm. Thus, this phase 2b study demonstrated that vadadustat raised and maintained hemoglobin levels in a predictable and controlled manner while enhancing iron mobilization in patients with nondialysis-dependent CKD.
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Kidney international · Sep 2016
Randomized Controlled TrialTreatment with patiromer decreases aldosterone in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
Elevated serum aldosterone can be vasculotoxic and facilitate cardiorenal damage. Renin-angiotensin system inhibitors reduce serum aldosterone levels and/or block its effects but can cause hyperkalemia. Patiromer, a nonabsorbed potassium binder, decreases serum potassium in patients with chronic kidney disease on renin-angiotensin system inhibitors. ⋯ Patients on patiromer had significant reductions in mean systolic/diastolic blood pressure (-6.70 ± 1.59/-2.15 ± 1.06 mm Hg), whereas those on placebo did not (-1.21 ± 1.89 mm Hg/+1.72 ± 1.26 mm Hg). Significant changes in plasma renin activity were found only in the placebo group (-3.90 ± 1.41 μg/l/hr). Thus, patiromer reduced serum potassium and aldosterone levels independent of plasma renin activity in patients with chronic kidney disease and hyperkalemia on renin-angiotensin system inhibitors.
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Kidney international · Mar 2016
Randomized Controlled TrialPerioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery.
Acute kidney injury (AKI) following cardiac surgery is closely interrelated with hemodynamic instability and sympathetic activity, and adversely influences prognosis. Here, we investigated in a randomized placebo-controlled trial whether dexmedetomidine, an α2 adrenoreceptor agonist, could prevent AKI after valvular heart surgery. Two hundred patients undergoing valvular heart surgery were randomly assigned to equal placebo or treatment groups. ⋯ The incidence of AKI, based on Acute Kidney Injury Network criteria, was significantly lower in the treatment group compared with the control group (14 vs. 33%). The dexmedetomidine group exhibited a significantly lower incidence of a composite of major morbidity end points (21 vs. 38%) and a significantly shorter length of intensive care unit stay (3 [2, 3] days vs. 3 [2, 4] days) compared with the control group. Thus, perioperative infusion of dexmedetomidine effectively reduced both the incidence and severity of AKI, and improved outcome in patients undergoing valvular heart surgery without untoward hemodynamic side effects.
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Kidney international · Jan 2016
Randomized Controlled Trial Comparative StudyComparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis.
No previous study has compared mycophenolate mofetil (MMF) with low-dose cyclophosphamide (CYC) in the treatment of lupus nephritis (LN). To do so, we recruited patients with LN (class III, IV, or V) and randomized them to receive either low-dose CYC or oral MMF. Those with crescentic LN, a serum creatinine over 265 μmol/l, and neurological or pulmonary lupus were excluded. ⋯ Gastrointestinal symptoms were significantly more frequent in patients receiving MMF (52 vs. 4%). However, other adverse events were similar. Thus, low-dose intravenous CYC is comparable in safety and efficacy to oral MMF in the induction treatment of less severe LN.
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Kidney international · Oct 2015
Randomized Controlled Trial Multicenter Study Comparative StudyComparison of standard and accelerated initiation of renal replacement therapy in acute kidney injury.
In patients with severe acute kidney injury (AKI) but no urgent indication for renal replacement therapy (RRT), the optimal time to initiate RRT remains controversial. While starting RRT preemptively may have benefits, this may expose patients to unnecessary RRT. To study this, we conducted a 12-center open-label pilot trial of critically ill adults with volume replete severe AKI. ⋯ Two surviving patients, both randomized to standard RRT initiation, were still RRT dependent at day 90. No safety signal was evident in either arm. Our findings can inform the design of a large-scale effectiveness randomized control trial.