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Nephrolithiasis: A Paleolithic Perspective and Physiological Approach to Prevention.
Calyani Ganesan1, Lynda Frassetto2, Alan C Pao1,3,4
1Division of Nephrology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA;
Annual Review of Medicine
|January 27, 2026
Summary
The modern human diet, high in sodium and acid precursors, significantly increased the risk of nephrolithiasis (kidney stones) compared to the Paleolithic diet. Adopting ancient dietary patterns may reduce stone risk.
Area of Science:
- Evolutionary Medicine
- Nephrology
- Nutritional Science
Background:
- Nephrolithiasis (kidney stones) is a prevalent condition with complex etiologies.
- The human diet has undergone drastic changes over evolutionary history, particularly in the last 10,000 years.
Purpose of the Study:
- To explore the Paleolithic diet's influence on nephrolithiasis risk.
- To investigate the impact of the agricultural and industrial food production revolutions on kidney stone formation.
Main Methods:
- Review of evolutionary and historical dietary evidence.
- Analysis of the shift from a high-potassium, low-sodium, alkali-rich Paleolithic diet to a modern diet.
Main Results:
- The Paleolithic diet was characterized by high potassium, low sodium, and high alkali precursors.
- Modern diets, influenced by agriculture and industrialization, are high in sodium and acid precursors, increasing stone risk.
- The abrupt dietary shift challenged renal homeostasis, elevating stone formation risk.
Conclusions:
- A return to Paleolithic-like dietary patterns may mitigate kidney stone risk.
- While medications like thiazides, alkali, and empagliflozin show potential, further clinical trials are necessary to confirm their efficacy in preventing stone recurrence.
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