People who develop kidney stones show approximately twice the risk of developing kidney cancer compared with those without kidney stones, with the relationship observed across patient subgroups, results from a systematic review and meta-analysis show.

“These findings highlight the importance of enhanced cancer surveillance in patients with a history of kidney stones and suggest the need for further research into shared pathophysiologic mechanisms and potential preventative strategies,” reported the authors of the study published in the Canadian Urological Association Journal.

Kidney stone disease, which affects approximately 10% of adults at some point in their lifetime, has been linked to an increased risk for chronic kidney disease (CKD), urinary tract infections, and kidney cancer. The latter is of notable concern, as kidney cancer is considered the most aggressive of urologic cancers, with a 5-year mortality rate of 22%, the authors noted.

The risk related to kidney stones was evaluated in a meta-analysis from 2015, but there have been no updated meta-analyses published since then. Therefore, first author Naeem Bhojani, MD, a professor of urology at the University of Montreal in Montreal, Quebec, Canada, and colleagues conducted the current systematic review and meta-analysis.

A systematic search of studies involving patients with kidney stones and renal cancer risk was conducted in MEDLINE, EMBASE, and CENTRAL (from inception through to December 2024). The search yielded 13 studies, including five cohort and eight case-control studies, conducted in eight countries across Asia, Europe, North America, and Australia.

Men made up 48%-68% of patients in the studies, and their ages ranged from 49 to 65.

Overall, a history of kidney stones was significantly associated with an increased risk for kidney cancer in 11 of the 13 studies.

The pooled risk ratio (RR) in the meta-analysis was 2.36 (P < .001), indicating that those with a history of kidney stones had approximately twice the risk of developing kidney cancer compared to those without kidney stones.

The elevated kidney cancer risk was observed across all subgroups that were evaluated, including differences in study design, geographic region, sex distribution, data source, type of control group, and year of the study publication.

The association between kidney stones and risk for kidney cancer was stronger in more recent studies than in older studies (RR = 3.08 vs 1.35; P < .001).

Notably, while the increased kidney cancer risk observed in the prior meta-analysis was only observed in men, the current analysis showed the cancer risk to be elevated in both women and men with a history of kidney stones, suggesting that “the underlying mechanisms may be independent of sex-specific factors,” the authors said.

Possible Mechanisms?

In general, the biological mechanisms linking kidney stone and kidney cancer are unclear; however, factors that have been speculated as playing a role include shared metabolic abnormalities or environmental exposures that could contribute to stone formation as well as carcinogenesis.

The stronger association between kidney stones and kidney cancer risk in more recent studies may reflect the emergence of CT as the gold standard for diagnosing and monitoring kidney stones, as “the high sensitivity of CT in detecting small renal lesions may have led to increased incidental discovery of kidney cancers in stone formers,” the authors wrote.

“This hypothesis is supported by the fact that most kidney cancers are diagnosed incidentally, and actively surveilled kidney stone patients undergo CT scans 10 times more frequently than those without stones,” they added.

The much higher rate of CT scans also raises speculation that the scans themselves could play a role in the higher cancer risk, the authors noted.

“Because ionizing radiation is a well-recognized carcinogen, increased exposure from repeated CT scans may partially account for the higher observed risk of kidney cancer,” they said.

“These hypotheses warrant further investigation to separate the contributions of diagnostic imaging from potential underlying biological mechanisms.”

Clinical Implications

While current guidelines do not recommend routine screening for kidney cancer in the general public, the findings suggest the possible justification of targeted screening of high-risk groups, including those with a history of kidney stones, the authors noted.

The findings further support the benefits of greater efforts in the prevention and management of kidney stones. 

“The shared risk factors between these conditions, such as obesity, smoking, and certain dietary habits, suggest that interventions targeting these conditions could potentially reduce the risk for [kidney stones and kidney cancer] simultaneously,” the authors wrote.

“Healthcare providers should consider informing patients with kidney stones about their potentially increased kidney cancer risk and emphasize the importance of consistent follow-up care and lifestyle modifications.”

The study received funding from Boston Scientific. Bhojani, Larry E. Miller, and Ben H. Chew reported consultancy with Boston Scientific, while Samir Bhattacharyya reported employment with the company.