Losartan reduces ensuing chronic kidney disease and mortality after acute kidney injury

Area of Science:

• Nephrology
• Cardiovascular Research
• Translational Medicine

Background:

• Acute kidney injury (AKI) is a known risk factor for developing chronic kidney disease (CKD).
• The mechanisms linking AKI recovery to subsequent CKD progression are not fully understood.
• Existing research suggests a potential role for the renin-angiotensin-aldosterone system in this transition.

Purpose of the Study:

• To investigate the role of angiotensin II type 1a (AT1a) receptor signaling in the progression from AKI to CKD.
• To evaluate the therapeutic potential of blocking AT1a receptor signaling in mitigating AKI-induced CKD.

Main Methods:

• A murine model of severe AKI was established using right nephrectomy and left renal ischemia-reperfusion injury.
• Kidney injury, fibrosis, and gene expression were assessed post-AKI.
• Mice received losartan (AT1a receptor blocker), hydralazine (antihypertensive), or vehicle starting 4 weeks after AKI for 5 months.
• Outcomes measured included mortality, blood pressure, albuminuria, azotemia, and kidney fibrosis.

Main Results:

• Despite initial functional recovery, AKI mice exhibited progressive fibrosis, hypertension, albuminuria, and azotemia, along with increased mortality.
• Losartan administration significantly attenuated these adverse outcomes, restoring parameters to control levels.
• Hydralazine controlled blood pressure but did not prevent CKD progression or reduce mortality.

Conclusions:

• Angiotensin II type 1a receptor signaling is a key mechanism driving CKD development after AKI.
• Targeting AT1a receptors with losartan offers a promising therapeutic strategy to prevent or slow CKD progression and reduce mortality post-AKI.