Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018

Introduction Smoking is a recognized risk factor for chronic kidney disease (CKD), and cotinine and hydroxycotinine are tobacco metabolites that can be used to quantify smoking. This study evaluated their relationship with CKD in smokers. Methods This secondary dataset analysis is based on National...

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Main Authors: Shili Zhao, Shijing Zheng, Zhiqiang Liu, Yue Xu, Ning Jia, Cihang Lu, Yaning Wang
Format: Article
Language:English
Published: European Publishing 2025-03-01
Series:Tobacco Induced Diseases
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Online Access:https://www.tobaccoinduceddiseases.org/Hydroxycotinine-exhibits-a-stronger-association-with-chronic-kidney-disease-in-smokers,201969,0,2.html
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author Shili Zhao
Shijing Zheng
Zhiqiang Liu
Yue Xu
Ning Jia
Cihang Lu
Yaning Wang
author_facet Shili Zhao
Shijing Zheng
Zhiqiang Liu
Yue Xu
Ning Jia
Cihang Lu
Yaning Wang
author_sort Shili Zhao
collection DOAJ
description Introduction Smoking is a recognized risk factor for chronic kidney disease (CKD), and cotinine and hydroxycotinine are tobacco metabolites that can be used to quantify smoking. This study evaluated their relationship with CKD in smokers. Methods This secondary dataset analysis is based on National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2018. A crosssectional examination of a subsample of 2930 adult smokers aged ≥20 years was conducted to investigate the relationship between serum cotinine and its metabolite, hydroxycotinine, and CKD. Linear regression, multivariable-adjusted logistic regression, restrictive cubic splines, and subgroup analysis were utilized. Results Serum cotinine and hydroxycotinine levels were significantly elevated in CKD patients compared to the non-CKD population (230.00 vs 212.00 ng/ mL, p=0.02 for cotinine; 97.30 vs 74.70 ng/mL, p<0.001 for hydroxycotinine). In multivariable-adjusted logistic regression models, cotinine (≥316 ng/mL) showed a positive association solely with renal insufficiency (adjusted odds ratio, AOR=1.53; 95% CI: 1.07–2.17). In contrast, hydroxycotinine (≥124 ng/mL) was independently associated with three CKD indices: CKD diagnosis (AOR=1.61; 95% CI: 1.06–2.43), renal insufficiency (AOR=2.07; 95% CI: 1.33–3.23), and albuminuria (or proteinuria) (AOR=1.61; 95% CI: 1.06–2.43). Restricted cubic spline analyses revealed nonlinear dose-response relationships: hydroxycotinine exhibited broader negative associations with both eGFR and uACR (p<0.001), while cotinine showed threshold-dependent correlations with CKD risk (positive <180 ng/mL, attenuated above). Subgroup analyses further indicated that hydroxycotinine consistently correlated with CKD across demographics (e.g. males, age 0.05). Conclusions Elevated serum concentrations of cotinine and hydroxycotinine are positively associated with low glomerular filtration rate, albuminuria, and CKD in smokers, with hydroxycotinine demonstrating a stronger correlation. Smoking is established as a heightened risk factor for CKD, thus avoidance or reduction of smoking is strongly recommended.
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publisher European Publishing
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series Tobacco Induced Diseases
spelling doaj-art-79f2563d9f3f4b709ab3ceb38b894c792025-08-20T03:53:38ZengEuropean PublishingTobacco Induced Diseases1617-96252025-03-0123March11410.18332/tid/201969201969Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018Shili Zhao0https://orcid.org/0009-0000-2903-3955Shijing Zheng1Zhiqiang Liu2Yue Xu3Ning Jia4Cihang Lu5Yaning Wang6https://orcid.org/0009-0005-8773-3489Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of ChinaDivision of Nephrology, Beijing Yanqing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of ChinaDivision of Nephrology, Beijing Yanqing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of ChinaDivision of Nephrology, Beijing Yanqing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of ChinaDivision of Nephrology, Beijing Yanqing Hospital of Traditional Chinese Medicine, Beijing, People’s Republic of ChinaDivision of Endocrinology and Metabolic Diseases, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of ChinaDepartment of Nephrology, Binzhou Medical University Hospital, Binzhou, People’s Republic of ChinaIntroduction Smoking is a recognized risk factor for chronic kidney disease (CKD), and cotinine and hydroxycotinine are tobacco metabolites that can be used to quantify smoking. This study evaluated their relationship with CKD in smokers. Methods This secondary dataset analysis is based on National Health and Nutrition Examination Survey (NHANES) data from 2013 to 2018. A crosssectional examination of a subsample of 2930 adult smokers aged ≥20 years was conducted to investigate the relationship between serum cotinine and its metabolite, hydroxycotinine, and CKD. Linear regression, multivariable-adjusted logistic regression, restrictive cubic splines, and subgroup analysis were utilized. Results Serum cotinine and hydroxycotinine levels were significantly elevated in CKD patients compared to the non-CKD population (230.00 vs 212.00 ng/ mL, p=0.02 for cotinine; 97.30 vs 74.70 ng/mL, p<0.001 for hydroxycotinine). In multivariable-adjusted logistic regression models, cotinine (≥316 ng/mL) showed a positive association solely with renal insufficiency (adjusted odds ratio, AOR=1.53; 95% CI: 1.07–2.17). In contrast, hydroxycotinine (≥124 ng/mL) was independently associated with three CKD indices: CKD diagnosis (AOR=1.61; 95% CI: 1.06–2.43), renal insufficiency (AOR=2.07; 95% CI: 1.33–3.23), and albuminuria (or proteinuria) (AOR=1.61; 95% CI: 1.06–2.43). Restricted cubic spline analyses revealed nonlinear dose-response relationships: hydroxycotinine exhibited broader negative associations with both eGFR and uACR (p<0.001), while cotinine showed threshold-dependent correlations with CKD risk (positive <180 ng/mL, attenuated above). Subgroup analyses further indicated that hydroxycotinine consistently correlated with CKD across demographics (e.g. males, age 0.05). Conclusions Elevated serum concentrations of cotinine and hydroxycotinine are positively associated with low glomerular filtration rate, albuminuria, and CKD in smokers, with hydroxycotinine demonstrating a stronger correlation. Smoking is established as a heightened risk factor for CKD, thus avoidance or reduction of smoking is strongly recommended.https://www.tobaccoinduceddiseases.org/Hydroxycotinine-exhibits-a-stronger-association-with-chronic-kidney-disease-in-smokers,201969,0,2.htmlsmokecotininehydroxycotininechronic kidney disease
spellingShingle Shili Zhao
Shijing Zheng
Zhiqiang Liu
Yue Xu
Ning Jia
Cihang Lu
Yaning Wang
Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
Tobacco Induced Diseases
smoke
cotinine
hydroxycotinine
chronic kidney disease
title Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
title_full Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
title_fullStr Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
title_full_unstemmed Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
title_short Hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine: Evidence from NHANES 2013–2018
title_sort hydroxycotinine exhibits a stronger association with chronic kidney disease in smokers when compared to cotinine evidence from nhanes 2013 2018
topic smoke
cotinine
hydroxycotinine
chronic kidney disease
url https://www.tobaccoinduceddiseases.org/Hydroxycotinine-exhibits-a-stronger-association-with-chronic-kidney-disease-in-smokers,201969,0,2.html
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