Poor Sleep and Kidney Function Could Drive Severe Liver Disease

Credit: Unsplash / Greg Pappas

A combination of poor sleep health and kidney function are linked to a higher risk of developing a severe form of metabolic dysfunction-associated steatotic liver disease (MASLD), according to new study findings.

The research, from an international team of clinical investigators, additionally found that impaired kidney function could "partially mediate" the link between sleep and new-onset MASLD. The investigators originally sought to analyze the potential causes and effects of renal function in the link between sleep and severe MASLD risk. As they noted, up to one in five patients with MASLD are at risk of developing metabolic dysfunction-associated steatohepatitis (MASH)—a condition closely tied to a high risk of cirrhosis.

Their study used data from the UK Biobank, that which included more than 300,000 individual patients without prior liver disease. Mean patient age was 56 years old; 95 percent were White and 56 percent were female. The team collected data on patient lifestyle, sociodemographics, and renal function biomarkers, including urea, urate, creatinine, and cystatin C.

Poor sleep was assessed using five self-reported behaviors: sleep duration, chronotype, insomnia, snoring, and daytime sleepiness. The team defined high-risk sleep behaviors as an inadequate sleep duration (less than seven hours a day or more than eight hours a day), evening chronotype, frequent insomnia, snoring, and often daytime sleepiness. Each sleep behavior was given a score of zero (low poor sleep risk) or one (high poor sleep risk).

New-onset severe MASLD was identified through relevant hospital admission data, cancer registries, or death registries during follow-up. Over a median follow-up of 12.1 years, 2303 participants were diagnosed with new-onset severe MASLD. Investigators observed participants who developed severe MASLD had a greater waist-to-hip ratio, lower Townsend deprivation index scores, lower physical activity levels, were more likely to smoke, and had a greater prevalence of diabetes and high blood pressure compared to participants without new-onset severe MASLD.

Investigators assessed the associations between poor sleep and renal function with the increased risk of MASLD using multivariable Cox models, traditional mediation, and two-step Mendelian randomization analyses.

Inadequate sleep duration, frequent insomnia, snoring, and often daytime sleepiness were linked to a 19 to 37 percent increased risk of new-onset severe MASLD. Investigators observed a dose-response relationship between a poor sleep score and the risk of new-onset severe MASLD. Compared to participants with a low poor sleep score, participants with a high poor sleep score had an increased risk of new-onset severe MASLD.

As for renal function indicators, serum cystatin C and urate were associated with the risk of new-onset severe MASLD. Investigators observed a significant dose-response relationship between renal function biomarkers and new-onset severe MASLD. Participants with a high renal function biomarker score had a three-fold greater risk of developing severe MASLD, compared to participants with a low score.

Furthermore, low eGFR scores were linked to a greater risk of severe MASLD. Low eGFRcys had a two-fold greater risk of severe MASLD, compared to participants with high levels of eGFRcys.

Participants with poor sleep and the greatest renal function biomarker scores had a more than five-fold greater risk of severe MASLD, compared to those with healthy sleep patterns and the lowest renal function biomarker scores. The renal function biomarker score explained 10.08 percent of the correlations between poor sleep scores and the risk of new-onset severe MASLD.

“Our study demonstrates that sleep parameters and renal function indicators were independently and jointly associated with the risk of developing new-onset severe MASLD,” investigators wrote.

Analyses also showed a causal link between insomnia and new-onset severe MASLD with chronic kidney disease mediating the relationship. Ultimately, the study underscored the bidirectional communication of the liver-kidney axis and offered modifiable strategies to prevent MASLD.

“These findings not only suggest that interventions targeting sleep and renal function improvement could reduce the incidence and progression of MASLD but also highlight the bidirectional communication of the liver–kidney axis,” investigators wrote. “The potential mechanisms underpinning the effects of sleep and renal function on MASLD warrant further investigation.”

An original version of this article was published on sister site HCPLive.