Poor Sleep, Renal Function Linked to Risk of Developing New-Onset MASLD

A new study discovered poor sleep and renal function were associated with an increased risk of new-onset severe metabolic dysfunction-associated steatotic liver disease (MASLD).¹

“Another key finding of the present study is that renal function impairment partially mediates the association between sleep and new-onset severe MASLD incidence,” wrote investigators, led by Tian Tian, MD, from Anhui Medical University in China.

Up to 20% of people with MASLD may develop metabolic dysfunction-associated steatohepatitis, which can then lead to cirrhosis.² Investigators sought to investigate the potential causal interrelationships and mediating roles of renal function impairment in the association between sleep and severe MASLD risk.¹

The study involved 305,257 UK Biobank participants (mean age: 56.46 years; 95.04% White, 55.64% female) without prior liver disease. Data were collected on lifestyle, sociodemographics, and renal function biomarkers, including urea, urate, creatinine, and cystatin C.

Poor sleep was assessed using 5 self-reported behaviors: sleep duration, chronotype, insomnia, snoring, and daytime sleepiness. The team defined high-risk sleep behaviors as an inadequate sleep duration (< 7 hours a day or > 8 hours a day), evening chronotype, frequent insomnia, snoring, and often daytime sleepiness. Each sleep behavior was given a score of 0 (low poor sleep risk) or 1 (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% - 37% 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 (P < .001). 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 (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.34 – 2.19).

As for renal function indicators, serum cystatin C and urate were associated with the risk of new-onset severe MASLD (P < .001). Investigators observed a significant dose-response relationship between renal function biomarkers and new-onset severe MASLD (HR, 1.32; 95% CI, 1.27 – 1.36). Participants with a high renal function biomarker score had a 3.19-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 (P < .010). Low eGFRcys had a 2.08-fold greater risk of severe MASLD, compared to participants with high levels of eGFRcys (HR, 2.08; 95% CI, 1.76 – 2.46; P < .001).

Participants with poor sleep and the greatest renal function biomarker scores had a 5.45-fold greater risk of severe MASLD, compared to those with healthy sleep patterns and the lowest renal function biomarker scores (95% CI, 3.88 – 7.66; P < .001). The renal function biomarker score explained 10.08% 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 (odds ratio [OR] 1.23; 95% CI, 1.11–1.35) 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.”

References

1. ^{Tian T, Zeng J, Li YC, et al. Joint effects of sleep disturbance and renal function impairment on incident new-onset severe metabolic dysfunction-associated steatotic liver disease. Diabetes Obes Metab. Published online August 8, 2024. doi:10.1111/dom.15841}
2. ^{Metabolic Dysfunction-Associated Steatotic Liver Disease. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/22437-non-alcoholic-fatty-liver-disease. Accessed August 19, 2024.}