Gallbladder removal surgery is among the most common operations in the United States. But does this procedure increase the risk of kidney cancer? The evidence so far has been mixed and limited in scale.
Recently, an analysis of two large Swedish and United Kingdom research cohorts uncovered more definitive clues on this topic.
Gallstones affect 1 in 4 western adults
Gallstones are hardened deposits of digestive fluid in the gallbladder. The gallbladder stores and concentrates bile, a fluid produced by the liver that helps digest fats. Bile contains cholesterol, bile salts, bilirubin, and other compounds. Gallstones form when bile has too much cholesterol or bilirubin.
Gallstones affect up to a quarter of adults in Western countries [1]. While many remain symptom-free, around 20% develop complications such as abdominal pain, infection, and inflammation of the gallbladder [2]. This often requires surgical removal of the gallbladder, known as cholecystectomy.
Gallstones and potential risk of kidney cancer
Following cholecystectomy, the amount of bile salts in the urine rises. These compounds can potentially damage kidneys and instigate cancer development over time [3]. Therefore, cholecystectomy is believed to increase the risk of kidney cancer.
However, the association between gallbladder removal and subsequent kidney cancer development may not be that straightforward. To clarify the potential link between cholecystectomy and kidney cancer, researchers analyzed clinical data of gallstones and kidney cancer patients [4].
Analyzing swedish cholecystectomy patients
The researchers first looked at cholecystectomy rates, kidney cancer diagnoses, and other data from Swedish national registries spanning over 50 years.
Of 628,000 patients undergoing gallbladder removal, 2627 later developed kidney cancer. The relative risk was 17% higher compared to matched controls who did not have surgery.
Short-term risk spike after gallbladder removal
In the first 6 months following cholecystectomy, kidney cancer risk rose almost 4-fold as compared to the general population. However, the reasons may involve detection bias.
Since abdominal imaging is common around the time of gallbladder surgery, cancers coincidentally present may get spotted sooner than they would otherwise. This likely explains the initial spike in diagnoses.
However, the study found risks remained elevated even when excluding cases were diagnosed in the first few years after cholecystectomy. This points to a true biological link.
Gallbladder removal at young age has higher kidney cancer risk
Another important finding was that patients undergoing cholecystectomy before the age of 40 years had a 55% higher kidney cancer rate than those over 60 years of age. The risk was intermediate for middle-aged adults.
This suggests cholecystectomy earlier in life, which allows more time for bile-related kidney damage to accumulate, is associated with greater odds of eventually developing cancer.
Causal link between gallstones and kidney cancer supported
To further validate these results, the team used a technique called Mendelian randomization using United Kingdom biobank data.
People inherit certain gene variants that make them more prone to developing gallstones. Since gene assignment is random at conception, this creates a "natural experiment" to infer causality.
The analysis found gallstone genetic risk also increased kidney cancer odds, providing evidence that it is not surgery alone but the stones themselves that drive cancer risk. Known kidney cancer risk factors like smoking partially mediated the effect.
What should patients know?
While provocative, these findings do not imply that gallbladder removal significantly increases kidney cancer risk for most people. But they do have important implications:
Kidney cancer screening may be warranted years after cholecystectomy, especially if done at a young age.
Research into anti-inflammatory drugs and supplements to lower kidney damage from bile acids is needed.
Being aware of these possible risks allows patients to make informed choices about timing elective gallbladder removal and subsequent kidney cancer screening. Further studies are warranted to clarify the biological mechanisms linking gallstones to cancer development.
References
1. K. S. Gurusamy and B. R. Davidson, “Gallstones,” BMJ, vol. 348, p. g2669, Apr. 2014, doi: 10.1136/bmj.g2669.
2. H.-U. Marschall and C. Einarsson, “Gallstone disease,” Journal of Internal Medicine, vol. 261, no. 6, pp. 529–542, 2007, doi: 10.1111/j.1365-2796.2007.01783.x.
3. S. Li, C. Li, and W. Wang, “Bile acid signaling in renal water regulation,” American Journal of Physiology-Renal Physiology, vol. 317, no. 1, pp. F73–F76, Jul. 2019, doi: 10.1152/ajprenal.00563.2018.
4. E. Kharazmi et al., “Gallstones, Cholecystectomy, and Kidney Cancer: Observational and Mendelian Randomization Results Based on Large Cohorts,” Gastroenterology, vol. 165, no. 1, pp. 218-227.e8, Jul. 2023, doi: 10.1053/j.gastro.2023.03.227.
