Endothelin and tubulointerstitial renal disease

Area of Science:

• Nephrology
• Molecular Biology
• Pathophysiology

Background:

• Endothelin (ET) system components are present in renal tubular cells.
• Acute kidney injury (AKI) and polycystic kidney disease (PKD) involve tubular pathology.
• The ET system's role in these diseases is under investigation.

Purpose of the Study:

• To review current knowledge on the endothelin system's involvement in AKI and PKD.
• To evaluate the translational potential of ET-targeting therapies from preclinical studies to human applications.

Main Methods:

• Review of preclinical and clinical studies on the ET system in renal tubular diseases.
• Analysis of studies investigating ET receptor antagonists in AKI and PKD models.
• Examination of the balance between ETA and ETB receptor activity.

Main Results:

• Preclinical studies suggest ET system involvement in ischemia-reperfusion injury and radiocontrast-induced AKI, but clinical translation has been unsuccessful.
• ET system activation is noted in sepsis-induced AKI models, with variable preclinical efficacy of ET blockers.
• While the ET system is crucial in PKD pathophysiology, selective ET receptor targeting in animal models has yielded disappointing results, highlighting the need for balanced ETA/ETB receptor action.

Conclusions:

• The ET system is implicated in the pathogenesis of renal tubulointerstitial diseases, including AKI and PKD.
• Despite extensive preclinical data, experimental findings on ET blockers have not translated to successful human therapies for these kidney conditions.
• A balanced interaction between ETA and ETB receptors is essential for maintaining kidney structure and function in cystic kidneys.