Does a history of chronic kidney stone disease, specifically with large monohydrate oxalate stones requiring repeated shockwave lithotripsy, contribute to the development of kidney cancer due to associated oxidative stress and inflammation?

From the Guidelines

There is limited evidence to suggest a direct link between chronic kidney stone disease and the development of kidney cancer, but repeated interventions like shockwave lithotripsy may contribute to oxidative stress and inflammation, potentially increasing cancer risk. Chronic kidney stones, particularly those requiring repeated interventions, can cause persistent inflammation and oxidative stress in kidney tissues, which are known potential contributors to cancer development 1. Monohydrate calcium oxalate stones can cause repeated injury to kidney cells during their formation and passage, and the interventions needed to remove them may increase risk. Additionally, the underlying metabolic conditions that cause stone formation might independently influence cancer risk. However, many people with long-term kidney stone disease never develop kidney cancer, and other factors like genetics, smoking, obesity, and hypertension play more significant roles in kidney cancer development.

Some studies suggest that oxidative stress plays a crucial role in the pathogenesis of atherosclerosis in chronic kidney disease (CKD) patients, and associations exist between increased oxidative stress, inflammation, and endothelial dysfunction, which may contribute to increased risk of cardiovascular disease 1. The determination of oxidative stress relies on the use of more stable surrogate markers, as oxidants have very short half-lives and cannot be reliably evaluated in the clinical situation.

Given the potential risks, it is advisable to maintain regular follow-up with a urologist or nephrologist who can monitor kidney health and function over time, especially in patients with a history of chronic kidney stones requiring repeated interventions like shockwave lithotripsy 1. Clinicians should obtain a repeat stone analysis, when available, especially in patients not responding to treatment, as a change in stone composition may account for the lack of response to dietary/medical therapy 1.

Key considerations for patients with chronic kidney stone disease include:

• Maintaining regular follow-up with a urologist or nephrologist to monitor kidney health and function
• Obtaining repeat stone analysis, when available, especially in patients not responding to treatment
• Managing underlying metabolic conditions that cause stone formation
• Reducing risk factors for kidney cancer, such as smoking, obesity, and hypertension
• Considering the potential risks and benefits of repeated interventions like shockwave lithotripsy.

From the Research

Association between Kidney Stone Disease and Kidney Cancer

• There is evidence to suggest that kidney stone disease, particularly with large monohydrate oxalate stones requiring repeated shockwave lithotripsy, may contribute to the development of kidney cancer due to associated oxidative stress and inflammation 2, 3, 4, 5.
• Studies have shown that chronic kidney disease (CKD) is characterized by increased levels of oxidative stress and inflammation, which can promote renal injury and damage to molecular components of the kidney 3.
• Mitochondrial dysfunction has also been implicated in the pathophysiology of kidney stone disease, particularly calcium oxalate stone formation, and may contribute to oxidative stress and tissue inflammation 4.
• A history of kidney stones has been associated with an increased risk of chronic kidney disease (CKD) in a meta-analysis of observational studies, suggesting a potential link between kidney stone disease and kidney cancer 6.

Mechanisms of Oxidative Stress and Inflammation

• Oxidative stress and inflammation can establish a vicious cycle of tissue injury and stone formation, with immune cells and pro-inflammatory cytokines playing a key role in the development of kidney stone disease 2.
• The production of reactive oxygen species (ROS) and the development of oxidative stress are common features of many renal and cardiovascular diseases, including hypertension, diabetes, and nephrolithiasis 5.
• Mitochondrial dysfunction can lead to oxidative stress and tissue inflammation, which can contribute to the formation of kidney stones and potentially increase the risk of kidney cancer 4.

Clinical Implications

• Targeting inflammation directly may prove to be a novel and suitable means of treatment for at least some types of kidney stone disease, particularly in patients experiencing recurrent stone episodes or with a well-defined metabolic cause such as uric acid or calcium oxalate stones 2.
• Lifestyle interventions that reduce oxidative stress and inflammation may be beneficial in preventing kidney stone formation and potentially reducing the risk of kidney cancer 3.