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β2-Adrenergic receptor agonism as a therapeutic strategy for kidney disease
Ali Kamiar1,2, Keyvan Yousefi1,2, Julian C Dunkley1,3
1Interdisciplinary Stem Cell Institute, University of Miami Leonard M. Miller School of Medicine, Miami, Florida.
Insights
Chronic kidney disease affects 14% of people, potentially leading to acute kidney injury (AKI). Research explores beta2-adrenergic receptors (β2ARs) for novel kidney disease treatments, targeting molecular pathways for nephroprotection.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Chronic kidney disease (CKD) affects 14% of the population and can progress to acute kidney injury (AKI), a condition with high mortality and limited treatment options.
- Hypertension, diabetes, and cardiovascular disease are major comorbidities associated with kidney disease.
- Beta2-adrenergic receptors (β2ARs) are present in various kidney structures and play roles in regulating renal blood flow, electrolyte balance, and tubular function.
Purpose of the Study:
- To review preclinical research on beta2-adrenergic receptor (β2AR) signaling in kidney diseases.
- To update on the molecular pathways and potential drug targets identified through β2AR research.
- To highlight the emerging field of nephroprotection via β2AR activation.
Main Methods:
- Review of preclinical studies investigating β2AR signaling in renal contexts.
- Analysis of molecular pathways involved in β2ARs' effects on kidney function.
- Identification of potential therapeutic targets for kidney-related diseases.
Main Results:
- β2ARs are expressed in multiple kidney regions and influence key physiological processes.
- β2AR signaling pathways interact with other intracellular mechanisms in the kidney.
- Preclinical research has identified potential drug targets for kidney diseases based on β2AR modulation.
Conclusions:
- Activation of β2ARs shows promise for nephroprotection.
- Further research is needed to understand the pharmacology and potential side effects of renal β2AR modulation.
- Several potential drug targets are under clinical development for kidney diseases.
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.
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