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 sK...

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Main Authors: Tao Hong, Zelong Lian, Chaojun Zhang, Weihuang Zhang, Zhennan Ye
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2498089
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author Tao Hong
Zelong Lian
Chaojun Zhang
Weihuang Zhang
Zhennan Ye
author_facet Tao Hong
Zelong Lian
Chaojun Zhang
Weihuang Zhang
Zhennan Ye
author_sort Tao Hong
collection DOAJ
description 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); p < 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.
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spelling doaj-art-e912a7d68cdc43ada89100ec7806e9952025-08-20T03:11:05ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2498089Hypertension modifies the association between serum Klotho and chronic kidney disease in US adults with diabetes: a cross-sectional study of the NHANES 2007–2016Tao Hong0Zelong Lian1Chaojun Zhang2Weihuang Zhang3Zhennan Ye4Department of Nephrology, Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Nephrology, Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Information Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Nephrology, Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaDepartment of Nephrology, Institute of Nephrology, and Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, and Key Laboratory of Prevention and Management of Chronic Kidney Disease of Zhanjiang City, Affiliated Hospital of Guangdong Medical University, Zhanjiang, ChinaContext 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); p < 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.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2498089Chronic kidney diseaseKlothohypertensiondiabetes mellitusinteraction
spellingShingle Tao Hong
Zelong Lian
Chaojun Zhang
Weihuang Zhang
Zhennan Ye
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
Renal Failure
Chronic kidney disease
Klotho
hypertension
diabetes mellitus
interaction
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Chronic kidney disease
Klotho
hypertension
diabetes mellitus
interaction
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2498089
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