MASH, MASLD Linked to Higher Risk of Kidney Stones

Patients with fatty liver disease, particularly those with metabolic dysfunction-associated steatotic liver disease (MASLD), are significantly more likely to develop kidney stones, according to a new study published in JGH Open.1

The findings reveal a strong metabolic link between 2 of the most common conditions in modern medicine and may reshape how clinicians approach kidney stone prevention in patients with liver-related metabolic disorders, write the researchers of the study.

The group called for prospective trials to validate these findings and clarify causal pathways, especially through biochemical studies examining liver-kidney metabolic interactions. | Image credit: Pakawadee - stock.adobe.com

Researchers analyzed data from more than 140 million hospitalizations across the United States, making the study one of the largest to explore the relationship between liver steatosis and nephrolithiasis (kidney stone disease, or KSD).

Across all hospitalized adults, the odds of having kidney stones were nearly twice as high in those with metabolic dysfunction-associated steatohepatitis (MASH) and more than 3 times higher in those with MASLD compared with individuals without liver fat accumulation. After full adjustment, MASLD remained the strongest predictor, with an odds ratio (OR) of 3.38, compared with 1.96 for MASH (both P < 0.0001).

“The observed correlations warrant increased clinical vigilance in managing patients with these comorbidities,” wrote the researchers.

The researchers used National Inpatient Samples from 2016 to 2020, identifying the hospitalizations involving diagnoses of MASLD, the disease formerly known as nonalcoholic fatty liver disease, and MASH, then compared these groups to patients without liver disease. Advanced logistic regression modeling was used to adjust for demographic, metabolic, and socioeconomic factors, including body mass index (BMI), type 2 diabetes, obesity, gout, and smoking.

Notably, when analyzed alongside traditional metabolic risk factors, fatty liver disease was more strongly linked to kidney stones than diabetes or gout, both long-recognized culprits in stone formation.

When comparing the 2 forms of liver disease directly, patients with MASLD had a higher prevalence of kidney stones (2.8%) than those with MASH (1.7%). The researchers noted that the finding challenges expectations, as MASH represents a more advanced stage of liver injury.

The study offered potential biochemical mechanisms linking fatty liver and kidney stones. Prior research suggests that impaired liver metabolism can reduce alanine glyoxylate aminotransferase activity, leading to higher oxalate levels in the bloodstream and urine, a key driver of calcium oxalate stone formation. Additionally, chronic oxidative stress and lipid accumulation may promote crystal nucleation in kidney tissue.

Consistent with prior studies,2 men were more likely to have kidney stones, while women, particularly premenopausal women, showed a protective effect, possibly due to estrogen’s influence on calcium and citrate balance. Geographic patterns also emerged: individuals living in the South Atlantic and Pacific regions had significantly higher kidney stone odds than those in the Northeast, aligning with the effects of warmer climates and dehydration risk.

The researchers emphasize that the findings should prompt clinicians to screen for kidney stones. or at least assess risk, in patients with known liver steatosis. They also argue for moving beyond BMI as the sole predictor of risk.1

“Of note, after adjusting for other variables, our analysis did not demonstrate a consistent incremental increase in the odds of KSD diagnosis with rising BMI values,” described the researchers.

The group called for prospective trials to validate these findings and clarify causal pathways, especially through biochemical studies examining liver-kidney metabolic interactions. They also highlight the need to integrate dietary data, medication history, and genetic markers in future analyses.

References

1. Habib T, Zaidan N, Jaber K, et al. Association of kidney stone disease with metabolic dysfunction associated liver disease and metabolic dysfunction associated steatohepatitis: a national inpatient sample study. Open J Gasrtroenterol Hepatol. Published online September 17, 2025. doi:10.1002/jgh3.70280

2. Ferraro PM, Taylor EN, Curhan GC. Factors associated with sex differences in the risk of kidney stones. Nephrol Dial Transplant. 2022;38(1):177-183. doi:10.1093/ndt/gfac037