Perfluoroalkyl substances and kidney function in chronic kidney disease, anemia, and diabetes

Abstract

Background

Anemia often complicates chronic kidney disease (CKD), leading to insufficient tissue oxygenation and hypoxic injury, the factor thought to underlie progression from CKD to renal failure. Perfluorocarbons are potent oxygen transporters used in organ preservation and synthetic blood development. Data are scarce on their relationship with kidney function, especially in diabetes where anemia and hypoxia are more prevalent. We investigated the relationship of perfluoroalkyl acids (PFAS) with kidney function and variation by diabetes and anemia status.

Methods

Data on 53,650 adults (5,210 with diabetes) were obtained from the C8 Health Project. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid, perfluorooctane sulfonate, and perfluorononanoic acid.

Findings

Each PFAS was positively associated with eGFR among those with CKD or anemia; this was the strongest among those with both CKD and anemia, followed by those with CKD uncomplicated by anemia. These relationships were more pronounced among those with diabetes (all P<0.01). In the absence of both CKD and anemia, PFAS was inversely associated with eGFR. Among persons with both anemia and diabetes, when further stratified by CKD stage, compared to an eGFR <30, ORs (95% CI) for being in the eGFR ≥ 90, 60–89, 45–59, and 30–45 range, respectively, were 3.20 (2.00–5.13), 2.64 (1.83–3.80), 3.18 (2.17–4.67), and 1.99 (1.38–2.86) for each ng/dL increase in PFHxS. Results were similar for each PFAS.

Interpretation

PFAS are inversely associated with kidney function in CKD and diabetes, with a stronger relation observed when anemia is present.

Keywords:

• diabetes
• anemia
• chronic kidney disease
• hypoxia
• perfluoroalkyl substances

Acknowledgments

This work was supported in part by the National Institutes of Health grant U54GM104942 to the West Virginia University Clinical and Translational Science Institute. The funding source had no involvement in the design of the study, the collection, analysis and interpretation of the data, the writing of the report, or the decision to submit this manuscript for publication. Parts of this paper were presented at the 75th and 76th Scientific Sessions of the American Diabetes Association, New Orleans, Louisiana, June 2016 and San Diego, California, June 2017. The poster’s 2016 abstract was published in the conference’s Late Breaking abstract booklet and the 2017 poster’s abstract was published in Diabetes 2017; 66 (S1).

Disclosure

The authors report no conflicts of interest in this work.