Cardiac and renal function in patients with type 2 diabetes who have chronic kidney disease: potential effects of bardoxolone methyl.
The intracellular and tissue balance of oxidant and antioxidant forces is a potential therapeutic target for a variety of agents in the treatment of complications due to chronic disease including diabetes mellitus and hypertension. There are a myriad of processes controlled at the level of genes, transcription factors, and protein messages that work to control the normal use of oxidative reactions within cells. Loss of control of these processes may lead to reversible dysfunction in many cell lines including the podocyte, renal tubular cells, and cardiac myocytes. Bardoxolone methyl is a novel nuclear regulator factor (Nrf-2) activator which works to tip the balance of effects towards antioxidation and as an observation made serendipitously, improves renal filtration function in humans after approximately 12 weeks of therapy. The improvement in estimated glomerular filtration can be up to 30% in those with stage 3 and 4 chronic kidney disease. However, experimental evidence suggests there may be a consequence of relative hyperfiltration in diseased kidneys as well as potential adverse effects on skeletal and cardiac myocytes. Only large, prospective randomized trials with carefully collected and adjudicated clinical outcomes will inform the research community on the therapeutic risks and benefits of this important new agent.
St John Hospital and Medical Center, Providence Hospital and Medical Centers, Departments of Medicine, St John Providence Health System, Detroit, MI, USA.
Peter A
PA
McCullough
Sajid
S
Ali
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002908:Chronic Disease; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology; D007677:Kidney Function Tests; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009828:Oleanolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D016877:Oxidants / Q000378:metabolism
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D016877:Oxidants; D009828:Oleanolic Acid; C445068:bardoxolone methyl