RESUMO
BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). This study investigated safety and efficacy of once-daily and 3-times-weekly dosing in patients with dialysis-dependent (DD)-CKD compared with darbepoetin alfa (DA). METHODS: This phase 3b, randomized (1:1:1; vadadustat once-daily [starting dose: 300 or 450 mg], vadadustat 3-times-weekly [starting dose: 600 or 750 mg], DA), open-label, active-controlled, noninferiority trial included conversion (weeks 0-20) and maintenance (weeks 20-52) periods. Primary and secondary efficacy endpoints were mean change in hemoglobin from baseline during the primary (PEP, weeks 20-26) and secondary (SEP, weeks 46-52) evaluation periods. Other endpoints included proportion of patients requiring ESA rescue (hemoglobin <9.5 g/dL or with increases in dose ≥50% or ≥100% in DA group). Safety endpoints included treatment-emergent adverse events (TEAEs) and serious AEs (SAEs). RESULTS: Least squares (LS) mean treatment difference between vadadustat once-daily and DA from baseline to PEP was -0.27 g/dL (95% CI, -0.55 to 0.01); the lower bound met the noninferiority threshold (-0.75 g/dL). The LS mean treatment difference between vadadustat 3-times-weekly and DA from baseline to PEP was -0.53 g/dL (95% CI, -0.80 to -0.25), which did not meet the lower bound noninferiority threshold. The LS mean change from baseline to the SEP between DA and vadadustat once-daily was -0.40 (95% CI, -0.79 to -0.02), and for vadadustat 3-times-weekly was -0.42 (95% CI, -0.81 to -0.02). Proportion of patients who received ESA rescue during weeks 2-52 was higher in the DA group than vadadustat groups. Similar TEAEs and treatment-emergent SAEs were observed across groups. CONCLUSIONS: Vadadustat once-daily, but not 3-times-weekly, was noninferior to DA in the correction and maintenance of hemoglobin in patients with DD-CKD converted from an ESA; safety profiles were similar across groups. TRIAL REGISTRATION: EudraCT 2019-004851-36/ClinicalTrials.gov identifier: NCT04313153.
RESUMO
Patients on maintenance hemodialysis are particularly prone to opportunistic infections because of their increased exposure to antibiotics, frequent vascular access, and altered cellular immunity. This case report discusses a 63-year-old African American patient on maintenance hemodialysis who presented with acute painful swelling of her left knee and fever. She was diagnosed to have septic arthritis, candidemia, and arteriovenous (AV) graft infection caused by Candida albicans. The management included removal of the infected AV graft, intravenous fluconazole, and arthrotomy with lavage. The Candida infection subsided, but the patient continued to have knee swelling because of chronic synovitis. We believe that this is the first case of acute Candida septic arthritis in a patient with end-stage renal disease, where hematogenous spread was proven by positive C. albicans cultures from the blood, AV graft, and synovial fluid.