Mr Tingfang Zhang1, Dr Zoe McArdle1, Ms Brianna Moore1, Ms Alyssa Muzio1, Professor Kate Denton1, Professor Robert Widdop1, Professor Sharon Ricardo1
1Monash University, Clayton, Australia
Biography:
Tingfang Zhang is a PhD candidate at Monash University with a background in biomedical science, holding both an Honours and a Master’s degree in the field. His research focuses on the progression from acute kidney injury (AKI) to chronic kidney disease (CKD), with a particular interest in investigating the therapeutic potential of angiotensin II type 2 receptor (AT2R) agonists. Tingfang is passionate about translating preclinical findings into potential clinical strategies for kidney disease and is actively contributing to advancements in renal pathophysiology.
Aim:
To investigate sex-specific differences in renal injury and progression from acute kidney injury (AKI) to chronic kidney disease (CKD) using a two-stage mouse model of unilateral ischemia-reperfusion injury (uIRI) followed by contralateral nephrectomy (uIRIx).
Background:
Sex differences in AKI are recognised, but their role in the progression to CKD remains unclear. While females may be protected against early injury, progression to CKD appears influenced by age, hormonal status, and intrinsic differences in cellular injury responses. The mechanisms driving these sex-specific outcomes are not well understood, underscoring the need for further investigation.
Method:
Male (8-10 weeks) and female (10-12 weeks) C57BL/6 mice underwent kidney uIRI (21-minute clamping), followed by uIRIx on day 14. Functional assessments included transdermal glomerular filtration rate (tGFR), urine output, and urinary albumin-to-creatinine ratio (uACR), monitored at 14, 42, 70 and 98 days post-uIRI. Kidney tissue was analysed using quantitative histopathology, collagen accumulation, glomerular injury, and immunohistochemistry (KIM-1) for tubular injury.
Results:
Male mice exhibited sustained reduction in GFR from Day 17 post-IRI (814.2±50.0 vs. 261.0±51.2 μl/min/100g, p<0.001), elevated urine output (p<0.001), and higher uACR (12.8±3.0 vs. 39.8±8.4 mg/g, p<0.05) compared to controls. Histologically, male kidneys showed increased collagen deposition (p<0.001), tubular dilation, glomerulosclerosis, and elevated KIM-1 expression (p<0.001) compared to controls. In contrast, female mice showed moderate GFR reduction (821.4±72.4 vs. 467.8±61.9μl/min/100g, p<0.01) compared to controls at day 42 with partial recovery by day 98, and smaller increase in urine output and collagen accumulation than male mice.
Conclusion:
This study reveals a distinct sex-specific response to AKI, with female mice exhibiting less severe injury and partial functional recovery, highlighting potential sex-specific differences in AKI-to-CKD transition and need for gender-tailored therapeutic strategies.
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