Aim: Multiple studies have investigated the association between alanine aminotransferase (ALT) and diabetes mellitus (DM); however, only a few studies have specifically examined the relationship between ALT and diabetic kidney disease (DKD). This study aimed to investigate the relationship between ALT and DKD using clinical data.
Methods: A cross-sectional study was conducted on 668 individuals that included non-DM (N=281), DM without DKD (N=160), and DKD (N=227) patients. A generalized additive model (GAM) was used to examine the dose–response relationship between ALT and DKD risk. We also analyzed the data from the US National Health and Nutrition Examination Survey (NHANES) 2015– 2018 using the same statistical methods; 4481, 1110, and 671 individuals were included in the non-DM, DM without DKD, and DKD groups, respectively.
Results: The changes in ALT activity among the non-DM, DM without DKD, and DKD groups showed a similar pattern in both our clinical data and the NHANES dataset. ALT activity increases with the onset of DM, whereas ALT activity decreases when DM progresses to DKD. The GAM revealed a nonlinear U-shaped relationship between ALT and DKD risk in the two datasets, and the lowest range of ALT was 40– 50 IU/L. Both lower (< 40 IU/L) and higher (> 50 IU/L) ALT activity were found to be positively associated with DKD risk.
Conclusion: A U-shaped nonlinear association between ALT and DKD was found in our clinical data and NHANES data. DKD risk was increased by both lower or higher ALT activity. To confirm the causality of nonlinear relationship, larger prospective studies or Mendelian randomization analysis are required.

Keywords: alanine aminotransferase, diabetic kidney disease, dose–response relationship, NHANES