β2-Adrenergic receptor agonism as a therapeutic strategy for kidney disease

Abstract

Approximately 14% of the general population suffer from chronic kidney disease that can lead to acute kidney injury (AKI), a condition with up to 50% mortality for which there is no effective treatment. Hypertension, diabetes, and cardiovascular disease are the main comorbidities, and more than 660,000 Americans have kidney failure. β2-Adrenergic receptors (β2ARs) have been extensively studied in association with lung and cardiovascular disease, but with limited scope in kidney and renal diseases. β2ARs are expressed in multiple parts of the kidney including proximal and distal convoluted tubules, glomeruli, and podocytes. Classical and noncanonical β2AR signaling pathways interface with other intracellular mechanisms in the kidney to regulate important cellular functions including renal blood flow, electrolyte balance and salt handling, and tubular function that in turn exert control over critical physiology and pathology such as blood pressure and inflammatory responses. Nephroprotection through activation of β2ARs has surfaced as a promising field of investigation; however, there is limited data on the pharmacology and potential side effects of renal β2AR modulation. Here, we provide updates on some of the major areas of preclinical kidney research involving β2AR signaling that have advanced to describe molecular pathways and identify potential drug targets some of which are currently under clinical development for the treatment of kidney-related diseases.