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

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.

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).

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).

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.