Aim The objective of this study was to explore the relationship between serum aspartate/alanine aminotransferase ratio (AST/ALT) and subsequent development of chronic kidney disease (CKD) in non-diabetic Japanese men and women in a 25-year follow-up study.

Methods The study included all middle-aged and older non-diabetic Japanese citizens who received health check-ups in Zentsuji, Kagawa, Japan (1998–2023). AST/ALT was classified into three categories: <1.0 (reference), 1.0–<1.5, and ≥1.5. Participant characteristics were compared by AST/ALT categories. The Weibull accelerated failure time model was used to examine the association between AST/ALT categories and subsequent CKD onset because the proportional hazards assumption was violated.

Results Of 6309 men and 9192 women, 2966 men and 4395 women remained in the final cohort. After a mean follow-up of 7.50 years for men and 8.34 years for women, 33.7% of men and 34.0% of women developed CKD. Women had higher AST/ALT than men. In women, a dose-response relationship was observed, with a 9% shorter survival time to CKD onset for AST/ALT ≥1.5 compared with AST/ALT <1.0. In contrast, men had a shorter survival time to CKD onset by point estimates, but the 95% confidence intervals crossed 1 in all models.

Conclusions In this study comparing the risks of CKD development in non-diabetic men and women by AST/ALT levels, a dose-response relationship was only observed in women. Differences in the distribution of AST/ALT by sex may have affected the results. Therefore, in non-diabetic Japanese women, AST/ALT may be used as an indicator of future CKD development.

Okawa has been employed by Zentsuji City as a part-time data analyst. Suzuki and Mitsuhashi have no competing interests to declare.

This research is self-funded and received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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We used data anonymized before receipt. The Ethics Committee of Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital approved this study (No. K1708-040). The Ethics committee waived the need for informed consent. This study was conducted in accordance with the Declaration of Helsinki and Japanese Ethical Guidelines for Medical and Biological Research Involving Human Subjects.

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