Hypertension modifies the association between serum Klotho and chronic kidney disease in US adults with diabetes: a cross-sectional study of the NHANES 2007-2016.

CONTEXT

The association between serum soluble Klotho (sKlotho) and chronic kidney disease (CKD) in individuals with diabetes mellitus (DM) remains controversial, and the influence of hypertension on this association is inconclusive.

OBJECTIVE

This study aims to investigate the joint association of sKlotho and hypertension with CKD prevalence in adults with DM.

METHODS

This cross-sectional study included 3,302 adults with DM from the National Health and Nutrition Examination Survey (2007-2016). Multivariate logistic regression analysis stratified by hypertension was used to assess the association between sKlotho and CKD prevalence. Moreover, the interaction between hypertension and sKlotho on CKD was evaluated.

RESULTS

Among individuals with DM, a significant association between sKlotho levels and CKD prevalence was observed only in those with hypertension. CKD prevalence was significantly lower in individuals with high sKlotho (≥ 806 pg/mL) than in those with low sKlotho (< 806 pg/mL) [adjusted OR = 0.54 (95% CI: 0.41-0.72);  < 0.001]. Moreover, a significant interaction between hypertension and sKlotho on CKD prevalence was observed among adults with DM [Multiplicative scale: OR = 0.65 (95% CI: 0.42-0.99); RERI = -0.80 (95% CI: -1.49 to -0.10); AP = -0.51 (95% CI: -0.90 to -0.12); SI = 0.44 (95% CI: 0.30-0.66)].

CONCLUSIONS

Among DM adults, hypertension modified the association between sKlotho levels and CKD prevalence. Both additive and multiplicative interactions were observed between hypertension and sKlotho levels on CKD. The causalities between hypertension, Klotho, and CKD in diabetic patients need further exploration, and underlying mechanisms warrants elucidation.