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March 3, 2026Annual Review of Medicine0 citationsOpen Access

Nephrolithiasis: A Paleolithic Perspective and Physiological Approach to Prevention

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CGCalyani GanesanLFLynda FrassettoAPAlan C. Pao

Key Points

  • Nephrolithiasis risk increases due to dietary shifts, particularly the rise in sodium and decrease in potassium.
  • The abrupt dietary transition 10,000 years ago correlates with higher incidences of stone formation in modern humans.
  • Analysis emphasizes the potential of a paleolithic diet to restore kidney homeostasis and reduce stone risk.
  • The effectiveness of medications like thiazides and alkali remains uncertain, indicating a need for further clinical trials.

Abstract

We take a Paleolithic perspective to account for why nephrolithiasis afflicts so many people and review evidence suggesting that the rapid shift in the human diet 10,000 years ago was a key event that increased stone risk in the modern era. For the past 2 million years, the diet of the hominid family was high in potassium, low in sodium, and high in alkali precursors. A series of technological advances in agriculture, animal husbandry, and industrial-scale food production transformed the human diet to contain more sodium, less potassium, and more acid precursors. This dietary shift was abrupt enough that the kidney was forced to maintain homeostasis at the expense of increasing stone risk. In theory, dietary patterns that resemble the Paleolithic diet should reduce stone risk. Medications like thiazides, alkali, and empagliflozin may improve urinary parameters associated with stone risk, but more clinical trials are needed to test their efficacy for reducing stone recurrence.

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Cite This Study

Ganesan et al. (2026) studied this question.

synapsesocial.com/papers/69a75b45c6e9836116a224ffhttps://doi.org/10.1146/annurev-med-043024-014508
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