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Bioenergetics: the evolutionary basis of progressive kidney disease
1Department of Pediatrics, The University of Virginia, Charlottesville, Virginia, United States.
Physiological Reviews
|March 30, 2023
Summary
Chronic kidney disease (CKD) stems from nephron vulnerability and evolutionary trade-offs. Understanding kidney bioenergetics may reveal new biomarkers and therapies for progressive CKD.
Area of Science:
- Evolutionary medicine
- Bioenergetics
- Nephrology
Background:
- Chronic kidney disease (CKD) affects over 10% globally, with rising prevalence.
- Nephron loss occurs with aging and injury, yet CKD causes remain unclear.
- Current biomarkers and therapies for CKD progression are limited.
Purpose of the Study:
- To explore evolutionary medicine and bioenergetics to explain heterogeneous nephron injury in CKD.
- To investigate how ancestral adaptations influence nephron vulnerability to stressors.
- To identify potential new biomarkers and therapies for progressive kidney disease.
Main Methods:
- Review of evolutionary medicine principles.
- Analysis of bioenergetic adaptations in mammalian nephrons.
- Integration of concepts of natural selection, metabolic plasticity, and antagonistic pleiotropy.
Main Results:
- Evolutionary adaptations for ancestral environments shape nephron vulnerability to modern stressors (ischemia, hypoxia, toxins).
- Metabolic plasticity and trade-offs, driven by energy allocation and reproductive fitness, contribute to nephron loss.
- Aging can reveal maladaptive traits (antagonistic pleiotropy) leading to cell fate decisions and kidney damage.
Conclusions:
- Understanding nephron bioenergetic adaptations to ancestral and contemporary environments is key.
- This approach may yield novel biomarkers for early detection of kidney disease.
- New therapeutic strategies targeting bioenergetic pathways could slow CKD progression and reduce global burden.
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