"Adenosine an old player with new possibilities in kidney diseases": Preclinical evidences and clinical perspectives

Area of Science:

• Nephrology
• Pharmacology
• Molecular Biology

Background:

• Renal injury stems from diverse causes including ischemia reperfusion, drug toxicity, and radio contrast agents.
• Four adenosine receptor subtypes (A1, A2A, A2B, A3) exhibit varied roles in kidney physiology and pathology.
• Adenosine receptors are implicated in acute kidney injury, chronic kidney disease, and nephritis.

Purpose of the Study:

• To review the multifaceted roles of adenosine receptor subtypes in kidney diseases.
• To explore the therapeutic potential of targeting adenosine receptors for renal protection and treatment.
• To discuss challenges and future directions for clinical applications of adenosine receptor modulators.

Main Methods:

• Literature review of studies on adenosine receptors in various renal injury models.
• Analysis of experimental findings regarding the activation or inhibition of specific adenosine receptor subtypes.
• Examination of clinical trial outcomes and challenges associated with adenosine receptor-targeted therapies.

Main Results:

• A1 receptor activation protects against acute kidney injury by improving hemodynamics and reducing tubular necrosis.
• A2A receptor activation influences macrophage phenotype in nephritis models; adenosine kinase inhibitors promote A2A stimulation.
• A3 receptor inhibition shows antioxidant, immunosuppressive, and anti-fibrotic effects, requiring further investigation.

Conclusions:

• Adenosine receptor modulation presents a potential therapeutic strategy for kidney diseases.
• Clinical success requires well-designed trials, possibly using agents with limited brain penetration to avoid neurological side effects.
• Further research is needed to fully elucidate the benefits of targeting specific adenosine receptor subtypes in diverse renal injury contexts.