Sex Differences in Renal Pathophysiology
Summary
Our understanding of how biological sex shapes the pathophysiology of the kidney has expanded markedly. Men and women differ in the prevalence, progression and outcome of many renal conditions. Epidemiological studies reveal that men are more susceptible to acute kidney injury and display more rapid progression to chronic kidney disease, whereas women often exhibit a degree of protection until the post-menopausal period. These differences arise from interactions between sex hormones, sex chromosomes and renal cellular mechanisms. Oestrogens promote vasodilatation, enhance antioxidant pathways and support tubular integrity, while androgens are linked to pro-inflammatory signalling and altered mitochondrial function. At a structural level, glomerular filtration and tubular reabsorption display sex-specific regulation, influencing susceptibility to nephrotoxic insults. Furthermore, immune cell infiltration, fibrotic remodelling and endothelial function within the kidney reflect a sexual dimorphism that informs both disease risk and therapeutic response. Recognition of these mechanisms is guiding precision strategies in the management of acute and chronic kidney disease across sexes, underpinning more tailored diagnostic and treatment approaches.
Research from Nature Portfolio
Recent work has delineated how the response to acute renal injury diverges between sexes during the transition to chronic kidney disease. Experimental models of renal ischaemia in rats revealed that female animals mount an early antioxidant defence and maintain higher expression of adaptive factors such as hypoxia-inducible factor and endothelial nitric oxide synthase, which mitigates fibrotic remodelling and proteinuria over the long term. In contrast, males progressively develop oxidative stress, glomerular hypertrophy and interstitial fibrosis, culminating in sustained functional decline. Studies involving oophorectomy underscore the protective role of ovarian hormones in female renoprotection, highlighting potential avenues for sex-specific intervention in the prevention of chronic kidney disease after acute injury.
Sex Differences in Renal Pathophysiology publication trend
The graph below shows the total number of articles in sex differences in renal pathophysiology across all publications each year (not limited to Nature Index journals).
Technical terms
Glomerular filtration rate (GFR): A measure of the volume of fluid filtered by the glomeruli per unit time, indicating kidney function.
eGFR and mGFR: Estimated and measured GFR respectively; eGFR is calculated from serum biomarkers, mGFR is determined using clearance techniques.
Renal fibrosis: The accumulation of extracellular matrix components in the interstitium, leading to scarring and loss of function.
Macrophage polarization: The process by which macrophages acquire distinct functional phenotypes (M1 pro-inflammatory or M2 reparative) in response to stimuli.
Sexual dimorphism: The systematic physiological differences between males and females of a species, in this context relating to kidney structure and function.
References
- Unveiling mechanisms underlying kidney function changes during sex hormone therapy. Journal of Clinical Investigation (2025).
- Activation of GPER1 in macrophages ameliorates UUO-induced renal fibrosis. Cell Death & Disease (2023).
- Sex dimorphism in kidney health and disease: mechanistic insights and clinical implication. Kidney International (2024).
- Gender Differences in the Acute Kidney Injury to Chronic Kidney Disease Transition. Scientific Reports (2017).
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