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Publications

Journal Article Ahead of print

PubMed: 42933690 DOI: 10.1016/j.jhepr.2026.102070

Risk of Adverse Kidney Outcomes in Families with MASLD: A Population-Based Multigenerational Cohort Study.

JHEP Rep

Authors: Fahim Ebrahimi, Christian Eichhorn, Jiangwei Sun, David Bergman, Carole A Marxer, Hannes Hagström, Juan J Carrero, Jonas F Ludvigsson

Affiliations

  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland.
  • Department of Gastroenterology and Hepatology, Clarunis University Center for Gastrointestinal and Liver Diseases, Basel, Switzerland; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Division of Hepatology, Department of Upper GI, Karolinska University Hospital, Stockholm, Sweden; Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York, USA.

Abstract

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with chronic kidney disease (CKD), but whether the CKD excess risk extends to MASLD family members is unknown.

METHODS

Nationwide multigenerational cohort study involving family members of all Swedish adults with biopsy-proven MASLD (1969-2017) and matched general population comparators. In total, 37,250 MASLD first-degree relatives (FDRs: parents, siblings, offspring) and 9,159 MASLD spouses, as well as 194,327 comparator FDRs and 46,582 comparator spouses were followed until 2021. The primary endpoint was a composite of chronic kidney disease (CKD) diagnosis, kidney failure with replacement therapy (KFRT), or death from CKD. Cox regression was used to calculate adjusted hazard ratios (aHRs).

RESULTS

Over a median of 18.8 years, the incidence rate of the composite adverse kidney outcome was higher in MASLD FDRs vs. comparator FDRs (137 vs. 123/100,000 person years (PYs); aHR=1.11, 95%CI=1.01-1.21). Risk estimates for each single component were increased but did not attain statistical significance: CKD (aHR=1.10, 95%CI=0.99-1.21), KFRT (aHR=1.17, 95%CI=0.96-1.41), and death from CKD (aHR=1.25, 95%CI=0.68-2.30). Risks were most pronounced among siblings (aHR=1.21, 95%CI=1.03-1.42). MASLD spouses also had an increased risk of the primary endpoint (25 vs. 20/100,000PY; aHR=1.12, 95%CI=0.97-1.30).

CONCLUSIONS

First degree relatives of individuals with biopsy-proven metabolic dysfunction-associated steatotic liver disease have a slightly higher risk of adverse kidney outcomes, but absolute risks are low and do not motivate systematic screening. A similar risk increase in spouses, albeit statistically non-significant, may be compatible with a contribution of shared lifestyle and metabolic factors, although genetic and environmental influences cannot be definitely disentangled.

MeSH

Liver Diseases, Kidney Diseases, Incidence, Cohort Studies, Kidney, Biopsy, Liver, Spouses, Siblings, Risk Factors