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

Abstract

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

Environment-Wide Association Study of CKD

“…However, studies suggesting potential reverse causation, possibly owing to reduced kidney function, are accumulating. Polyfluoroalkyl substance concentrations were associated with decreased eGFR in people without CKD; however, these were associated with increased eGFR among patients with CKD (46). In addition, menopausal status can affect serum polyfluoroalkyl substance concentration, as menstruation is a well known excretion route of polyfluoroalkyl substance among women (47).…”

Perfluoroalkyl substances and likelihood of stroke in persons with and without diabetes

“…21,22 We have recently observed inverse relationships between PFAS and coronary heart disease that was more pronounced among those with diabetes 16 and between PFAS and kidney function and chronic kidney disease that was significantly stronger in those with diabetes. 23 Using the C8 Health Project population, we examined the relationship of serum PFAS with stroke and the potential modifying influence of diabetes in a large sample of Appalachian adults, a population with among the highest rates of both diabetes and stroke in the United States. 20,24…”

Associations between Exposures to Perfluoroalkyl Substances and Diabetes, Hyperglycemia, or Insulin Resistance: A Scoping Review

“…Overall, we are unable to make a conclusion about the relationship between PFAS exposures and T2D due to variability and limited evidence. However, several studies did investigate comorbidities that may contribute to, or result from, potential interactions between PFAS exposures and diabetes, such as obesity, renal disease, abnormal liver function, and cancers [ 96 , 97 , 98 ]. Because behavioral factors such as diet and exercise influence development and progression of T2D, it is possible that factors such as consuming convenience foods wrapped in PFAS-containing packaging or spending more sedentary time in contact with surfactant-treated materials could be both increasing PFAS exposures and also increasing risk for diabetes and other comorbidities.…”