An Early Decrease in Release of Aquaporin-2 in Urinary Extracellular Vesicles After Cisplatin Treatment in Rats

Area of Science:

• Nephrology
• Biochemistry
• Molecular Biology

Background:

• Aquaporin-1 (AQP1) and Aquaporin-2 (AQP2) are key proteins in renal water balance.
• Both AQP1 and AQP2 are present in urinary extracellular vesicles (uEVs).
• Cisplatin, a chemotherapy drug, is known to reduce renal AQP1 and AQP2 expression.

Purpose of the Study:

• To investigate the impact of cisplatin on the release of uEV-AQP1 and uEV-AQP2 in rats.
• To determine if uEV-AQP1 and uEV-AQP2 can serve as biomarkers for cisplatin-induced nephrotoxicity.

Main Methods:

• Rats were treated with cisplatin, and renal function was assessed via blood tests at various time points.
• The release of uEV-AQP1 and uEV-AQP2 was quantified over a 168-hour period post-treatment.

Main Results:

• Renal function showed minimal change at 24 hours but declined significantly later.
• uEV-AQP1 release showed a transient increase at 24 hours, followed by a decrease at 168 hours.
• uEV-AQP2 release decreased significantly at 24 hours and remained low throughout the study.

Conclusions:

• Decreased uEV-AQP2 levels may indicate early-stage cisplatin-induced renal impairment.
• Measuring both uEV-AQP1 and uEV-AQP2 in urine could help stage cisplatin-induced kidney injury.
• These findings highlight the potential of uEV-AQPs as non-invasive biomarkers for monitoring chemotherapy-related kidney damage.