Risk of CKD in biopsy-proven metabolic dysfunction-associated steatotic liver disease
Fahim Ebrahimi, Christian Eichhorn, Tracey G Simon, Jiangwei Sun, David Bergman, Carole A Marxer, Heba Alkhatib, Soran R Bozorg, Hannes Hagström, Juan J Carrero, Jonas F LudvigssonAbstract
Background and hypothesis
There is scarce long-term data on the risk of chronic kidney disease (CKD) in patients with biopsy-proven metabolic dysfunction-associated steatotic liver disease (MASLD). We hypothesize that the risk of CKD in MASLD is increased and may vary with worsening histological severity.
Methods
Nationwide matched cohort study including all Swedish adults with histologically confirmed MASLD from 1969 to 2017 (n = 11 082) without prior kidney disease [simple steatosis (n = 7 522), non-fibrotic metabolic dysfunction-associated steatohepatitis (MASH) (n = 1 257), non-cirrhotic fibrosis (n = 1 692) and cirrhosis (n = 611)]. Individuals were matched to ≤ 5 population comparators (n = 52 645). The primary endpoint consisted of incident CKD, kidney failure with replacement therapy (KFRT; initiation of dialysis or kidney transplant) or death from kidney disease. Multivariable Cox regression was used to estimate adjusted hazard ratios (aHRs). Individuals with MASLD with at least one sibling were compared to their full siblings.
Results
Over a median of 17.6 years, 878 individuals with MASLD (incidence rate [IR] 53.1/10 000 person-years) vs. 2 643 comparators (IR 27.4) developed the composite CKD outcome. This was equal to one additional composite outcome event in 39 individuals with MASLD followed for ten years and corresponded to an aHR of 1.85 (95% confidence interval [CI] 1.68 − 2.04). The HR increased with worsening histological severity of MASLD (Ptrend < 0.001). Individuals with MASLD were at an almost two-fold increased hazard of CKD (aHR 1.83; 95% CI 1.66 − 2.02) and three-fold increased hazard of KFRT (aHR 2.88; 95% CI 2.32 − 3.57). Findings were robust and consistent across sensitivity and secondary analyses, including when individuals with MASLD were compared to their full biological siblings.
Conclusion
Individuals with biopsy-proven MASLD were at higher risk of developing CKD compared to both the general population and siblings. Excess risks were evident across all histological stages of MASLD and increased with worsening histologic severity.