Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial

•We examined the relationship between PFAS and eGFR among prediabetic adults.•We found evidence of associations between plasma PFAS and adverse kidney function.•Baseline plasma PFAS was inversely associated with prospective measures of eGFR.•Lifestyle intervention did not modify the association.•We...

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Published inEnvironment international Vol. 148; p. 106375
Main Authors Lin, Pi-I D., Cardenas, Andres, Hauser, Russ, Gold, Diane R., Kleinman, Ken P., Hivert, Marie-France, Calafat, Antonia M., Webster, Thomas F., Horton, Edward S., Oken, Emily
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.03.2021
Elsevier
Subjects
Adult
Alkanesulfonic Acids
Diabetes Mellitus, Type 2
Diabetes Prevention Program
eGFR
Environmental Pollutants
Female
Fluorocarbons
Follow-Up Studies
Humans
Hypertension
Kidney
Kidney function
Male
Middle Aged
Per- and polyfluoroalkyl substances
Prediabetic adults
CDC
DPP
Sm-PFOS
FP
MeFOSAA
Per- and polyfluoroalkyl substances
DPPOS
PFNA
DASH
n-PFOS
PFAS
n-PFOA
FDR
DAGs
PFDA
Sb-PFOA
NIDDK
BMI
eGFR
Hypertension
LOD
EtFOSAA
PFHxS
Kidney function
PFOA
Prediabetic adults
GAM
Diabetes Prevention Program
Sm2-PFOS
IRB
NHANES
PFOS
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Abstract •We examined the relationship between PFAS and eGFR among prediabetic adults.•We found evidence of associations between plasma PFAS and adverse kidney function.•Baseline plasma PFAS was inversely associated with prospective measures of eGFR.•Lifestyle intervention did not modify the association.•We observed stronger effect among those with baseline hypertension. Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
AbstractList •We examined the relationship between PFAS and eGFR among prediabetic adults.•We found evidence of associations between plasma PFAS and adverse kidney function.•Baseline plasma PFAS was inversely associated with prospective measures of eGFR.•Lifestyle intervention did not modify the association.•We observed stronger effect among those with baseline hypertension. Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR >90 mL/min/1.73 m 2 ) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m 2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m ) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996–2002) trial and Outcomes Study (DPPOS, 2002–2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40–64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999–2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: −4.12, −0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.
ArticleNumber 106375
Author Hauser, Russ
Gold, Diane R.
Oken, Emily
Horton, Edward S.
Hivert, Marie-France
Webster, Thomas F.
Cardenas, Andres
Kleinman, Ken P.
Lin, Pi-I D.
Calafat, Antonia M.
AuthorAffiliation 8 Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA
3 Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
4 Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
9 Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
1 Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA
2 Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA
6 Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
7 Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA
5 Department of Biostatistics, School of Public Health and Human Sciences, University of Massachusetts Amherst, Amherst, MA, USA
AuthorAffiliation_xml – name: 9 Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
– name: 4 Channing Division of Network Medicine, Brigham and Women’s Hospital, Boston, MA, USA
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Keywords CDC
DPP
Sm-PFOS
FP
MeFOSAA
Per- and polyfluoroalkyl substances
DPPOS
PFNA
DASH
n-PFOS
PFAS
n-PFOA
FDR
DAGs
PFDA
Sb-PFOA
NIDDK
BMI
eGFR
Hypertension
LOD
EtFOSAA
PFHxS
Kidney function
PFOA
Prediabetic adults
GAM
Diabetes Prevention Program
Sm2-PFOS
IRB
NHANES
PFOS
Language English
License This is an open access article under the CC BY-NC-ND license.
Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
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Notes RH, DG, KPK, MFH, TW, ESH, EO, carried out the conceptualization of the study; PID, AC, and KPK designed the analytical methods and statistical models; PID implemented the formal analysis; EO, AMC, and ESH were responsible in data curation and providing; all authors were involved in the investigation throughout the study; PIL wrote the manuscript and all authors reviewed and revised the manuscript.
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Snippet •We examined the relationship between PFAS and eGFR among prediabetic adults.•We found evidence of associations between plasma PFAS and adverse kidney...
Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to...
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StartPage 106375
SubjectTerms Adult
Alkanesulfonic Acids
Diabetes Mellitus, Type 2
Diabetes Prevention Program
eGFR
Environmental Pollutants
Female
Fluorocarbons
Follow-Up Studies
Humans
Hypertension
Kidney
Kidney function
Male
Middle Aged
Per- and polyfluoroalkyl substances
Prediabetic adults
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Title Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial
URI https://dx.doi.org/10.1016/j.envint.2020.106375
https://www.ncbi.nlm.nih.gov/pubmed/33482440
https://pubmed.ncbi.nlm.nih.gov/PMC7929640
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