Association between serum alpha-klotho levels and the incidence of diabetic kidney disease and mortality in type 2 diabetes: evidence from a Chinese cohort and the NHANES database

Diabetol Metab Syndr. 2025 May 2;17(1):148. doi: 10.1186/s13098-025-01711-x.

ABSTRACT

BACKGROUND: The α-klotho is crucial in diabetes and its related complications. This study seeks to explore the link between α-klotho levels and the risk of diabetic kidney disease (DKD) as well as all-cause and cardiovascular mortality among individuals with type 2 diabetes mellitus (T2DM).

METHODS: The investigation involved 126 Chinese T2DM patients and 4,451 individuals from the National Health and Nutrition Examination Survey (NHANES) database. To evaluate the relationship between α-klotho levels and DKD risk, multivariate logistic regression was utilized. Additionally, restricted cubic spline (RCS) regression analysis was conducted to examine the nonlinear relationship between α-klotho levels and DKD incidence. RCS analysis was employed to explore the correlation between α-klotho and both all-cause and cardiovascular mortality.

RESULTS: In the Chinese cohort, α-klotho levels were notably elevated in T2DM group compared to DKD group. The NHANES data revealed a significant inverse relationship between α-klotho levels and DKD risk. Nonlinear analysis further illustrated a substantial nonlinear connection between α-klotho levels and DKD risk. Serum α-klotho levels below 880.78 pg/mL were linked to increased DKD risk in T2DM patients. When compared to the T2DM group, the DKD group had markedly higher all-cause and cardiovascular mortality rates, with the α-klotho low group (e.g., Q1) exhibiting lower survival compared to other groups. Cox regression findings indicated that elevated α-klotho levels could mitigate all-cause mortality in T2DM patients. The relationship between α-klotho levels and all-cause mortality was also nonlinear, with the minimal risk found at α-klotho levels between 776.95 pg/mL and 812.69 pg/mL, varying by gender.

CONCLUSION: There exists a notable association between α-klotho levels and DKD risk, along with mortality in T2DM patients, with varying effects based on gender. These results highlight the potential importance of α-klotho as both a biomarker and a therapeutic target.

PMID:40312464 | PMC:PMC12046805 | DOI:10.1186/s13098-025-01711-x