TY  - JOUR
A1  - de Zeeuw, Dick
A1  - Akizawa, Tadao
A1  - Agarwal, Rajiv
A1  - Audhya, Paul
A1  - Bakris, George L.
A1  - Chin, Melanie
A1  - Krauth, Melissa
A1  - Lambers Heerspink, Hiddo J.
A1  - Meyer, Colin J.
A1  - McMurray, John J.
A1  - Parving, Hans-Henrik
A1  - Pergola, Pablo E.
A1  - Remuzzi, Giuseppe
A1  - Toto, Robert D.
A1  - Vaziri, Nosratola D.
A1  - Wanner, Christoph
A1  - Warnock, David G.
A1  - Wittes, Janet
A1  - Chertow, Glenn M.
T1  - Rationale and Trial Design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: The Occurrence of Renal Events (BEACON)
JF  - American Journal of Nephrology
N2  - Background: Chronic kidney disease (CKD) associated with type 2 diabetes mellitus constitutes a global epidemic complicated by considerable renal and cardiovascular morbidity and mortality, despite the provision of inhibitors of the renin-angiotensin-aldosterone system (RAAS). Bardoxolone methyl, a synthetic triterpenoid that reduces oxidative stress and inflammation through Nrf2 activation and inhibition of NF-κB was previously shown to increase estimated glomerular filtration rate (eGFR) in patients with CKD associated with type 2 diabetes mellitus. To date, no antioxidant or anti-inflammatory therapy has proved successful at slowing the progression of CKD. Methods: Herein, we describe the design of Bardoxolone Methyl Evaluation in Patients with Chronic Kidney Disease and Type 2 Diabetes: the Occurrence of Renal Events (BEACON) trial, a multinational, multicenter, double-blind, randomized, placebo-controlled Phase 3 trial designed to determine whether long-term administration of bardoxolone methyl (on a background of standard therapy, including RAAS inhibitors) safely reduces renal and cardiac morbidity and mortality. Results: The primary composite endpoint is time-to-first occurrence of either end-stage renal disease or cardiovascular death. Secondary endpoints include the change in eGFR and time to occurrence of cardiovascular events. Conclusion: BEACON will be the first event-driven trial to evaluate the effect of an oral antioxidant and anti-inflammatory drug in advanced CKD.
KW  - clinical trial
KW  - diabetes mellitus
KW  - glomerular filtration rate
KW  - trial design
KW  - bardoxolone methyl
KW  - Nrf2
KW  - end-stage renal disease
KW  - cardiovascular death
KW  - chronic kidney disease
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196832
SN  - 0250-8095
SN  - 1421-9670
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 37
IS  - 3
ER  - 
TY  - JOUR
A1  - Macdougall, Iain C.
A1  - Bircher, Andreas J.
A1  - Eckhardt, Kai-Uwe
A1  - Obrador, Gregorio T.
A1  - Pollock, Carol A.
A1  - Stenvinkel, Peter
A1  - Swinkels, Dorine W.
A1  - Wanner, Christoph
A1  - Weiss, Günter
A1  - Chertow, Glenn M.
T1  - Iron management in chronic kidney disease: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference
JF  - Kidney International
N2  - Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the risk for acute reactions and other adverse effects.
KW  - chronic kidney disease
KW  - hypersensitivity
KW  - infections
KW  - iron
KW  - overload
KW  - oxidative stress
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191467
VL  - 89
IS  - 1
ER  -