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Why is chronic kidney disease progressive? Evolutionary adaptations and maladaptations
1Department of Pediatrics, The University of Virginia, Charlottesville, Virginia, United States.
American Journal of Physiology. Renal Physiology
|September 7, 2023
Summary
Evolutionary traits like limited nephron number and aging-related nephron loss contribute to chronic kidney disease (CKD). Understanding these evolutionary constraints may reveal new therapeutic targets for CKD.
Area of Science:
- Evolutionary biology
- Nephrology
- Physiology
Background:
- Global prevalence of chronic kidney disease (CKD) is increasing despite advances in renal physiology.
- Evolutionary trade-offs and ancestral adaptations influence CKD development across the lifespan.
- Cell cycle function is constrained by energy availability, impacting nephrogenesis and aging.
Purpose of the Study:
- To explore the evolutionary basis of chronic kidney disease (CKD).
- To understand how evolutionary traits shape CKD progression over a lifetime.
- To identify potential therapeutic targets by applying an evolutionary perspective to CKD.
Main Methods:
- Analysis of evolutionary traits influencing CKD: nephron number variation, aging-related nephron loss, and adaptive kidney growth.
- Examination of energy allocation constraints on fetal nephrogenesis and cell senescence.
- Application of evolutionary principles, including antagonistic pleiotropy, to explain CKD increase with aging.
Main Results:
- Three key evolutionary traits (nephron number, aging loss, adaptive growth) shape CKD.
- Energy prioritization can restrict fetal nephrogenesis, a CKD risk factor.
- Adaptive nephron hypertrophy accelerates cell senescence, increasing vulnerability and CKD risk with aging.
Conclusions:
- An evolutionary perspective reveals how ancestral adaptations and constraints contribute to CKD.
- Understanding cell cycle regulation, senescence, and hypertrophy in an evolutionary context is crucial.
- This approach may lead to novel therapeutic strategies for managing and treating chronic kidney disease.
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