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

Area of Science:

• Environmental Health
• Nephrology
• Epidemiology

Background:

• Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants detected globally.
• Previous research suggests potential adverse effects of PFAS on kidney function.
• The Diabetes Prevention Program (DPP) and its Outcomes Study (DPPOS) provide a unique cohort for longitudinal analysis.

Purpose of the Study:

• To investigate the longitudinal association between plasma PFAS concentrations and estimated glomerular filtration rate (eGFR).
• To determine if a lifestyle intervention modifies the relationship between PFAS and eGFR.
• To assess the impact of a PFAS mixture on kidney function.

Main Methods:

• Analysis of 875 participants from the DPP/DPPOS trial, with baseline PFAS measurements and repeated eGFR measures over ~14 years.
• Generalized linear mixed models were used to assess associations between six specific PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA) and eGFR.
• Quantile-based g-computation evaluated the effects of the PFAS mixture on eGFR.

Main Results:

• Elevated baseline plasma PFAS concentrations were inversely associated with eGFR during follow-up.
• Each quartile increase in the PFAS mixture was associated with a 2.26 mL/min/1.73 m² lower eGFR at 5 years post-intervention.
• The inverse association was stronger in participants with baseline hypertension; lifestyle intervention did not modify the association.

Conclusions:

• Longitudinal exposure to PFAS is associated with declining kidney function in prediabetic adults.
• Hypertension may increase susceptibility to the kidney-adverse effects of PFAS.
• Lifestyle interventions did not mitigate the negative impact of PFAS on eGFR in this cohort.