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Kidney stone disease: risk factors, pathophysiology and management

Nature Reviews Nephrology volume 21, pages 794–808 (2025)Cite this article

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Abstract

Nephrolithiasis is the most common health condition affecting the kidney and urinary tract and constitutes a major global health-care problem. The prevalence of nephrolithiasis has increased substantially over the past five decades, irrespective of age, sex or ethnicity. Kidney stones cause substantial morbidity, reduced quality of life and enormous health-care expenditure, largely due to their frequent recurrence. Furthermore, nephrolithiasis is now recognized as a systemic condition associated with increased risks of chronic kidney disease, cardiovascular disease, metabolic syndrome and low bone mass. Nephrolithiasis exhibits marked pathophysiological heterogeneity. Dietary and environmental exposures interact with genetic predisposition to shape individual disease risk. Calcium oxalate stones are most prevalent, commonly driven by hypercalciuria, hyperoxaluria, hypocitraturia and low urine volume, whereas the formation of uric acid and calcium phosphate stones is commonly linked to urinary pH. A comprehensive clinical evaluation can uncover underlying metabolic abnormalities, distinguish idiopathic, secondary and Mendelian forms of nephrolithiasis, identify systemic disease associations and guide therapy. Recurrence prevention requires individualized strategies that combine dietary and pharmacological interventions. For established stones, surgical management is effective, with ureteroscopy and percutaneous nephrolithotomy achieving high stone-free rates. Despite its considerable clinical and societal burden, nephrolithiasis remains under-recognized, underserved and under-researched. Greater awareness and investments in research, innovation and education are urgently needed.

Key points

  • Adults and children with recurrent kidney stone disease (KSD) can benefit from a metabolic evaluation, which can be used to identify metabolic abnormalities, exclude secondary and monogenic KSD, and recognize systemic disease manifestations.

  • Dietary interventions and pharmacotherapy for prevention of kidney stone recurrence should be tailored to the underlying pathophysiology, disease activity, comorbidities and specific needs of the patient.

  • Disease activity should be monitored regularly and treatment adjusted accordingly. Careful patient education and follow-up are key to long-term treatment success.

  • Patients must be empowered and supported to understand their disease, implement self-selected lifestyle changes and make informed choices on pharmaceutical and surgical interventions.

  • Crucial KSD knowledge gaps persist and require further investigation. Future research priorities include the development of novel treatment options and the generation of randomized clinical trial evidence that can inform the management of KSD.

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Fig. 1: Physicochemistry of kidney stone formation.
Fig. 2: Histopathology and pathogenesis of kidney stone formation.
Fig. 3: Pathophysiology of hypercalciuria.

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Acknowledgements

S.A.H. is a Wellcome Trust Clinical Career Development Fellow.

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Authors and Affiliations

  1. Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

    Matteo Bargagli, Martin Scoglio & Daniel G. Fuster

  2. Graduate School for Health Sciences, University of Bern, Bern, Switzerland

    Martin Scoglio

  3. Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK

    Sarah A. Howles

  4. Academic Endocrine Unit, Radcliffe Department of Medicine, University of Oxford, Oxford, UK

    Sarah A. Howles

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D.G.F. served as a consultant for Otsuka, Alnylam, Boehringer Ingelheim and Kyowa Kirin, and received unrestricted research grants from Otsuka, Boehringer Ingelheim and CSL Vifor. S.A.H. has received payment from CJ Medical and Boston Scientific for educational activities. The other authors declare no competing interests.

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Bargagli, M., Scoglio, M., Howles, S.A. et al. Kidney stone disease: risk factors, pathophysiology and management. Nat Rev Nephrol 21, 794–808 (2025). https://doi.org/10.1038/s41581-025-00990-x

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