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Review
. 2022 Oct 17;3(12):2174-2182.
doi: 10.34067/KID.0007962021. eCollection 2022 Dec 29.

Environmental Exposures and Kidney Disease

Abhijit V Kshirsagar  1 , Evan M Zeitler  1 , Anne Weaver  2 , Nora Franceschini  3 , Lawrence S Engel  3
Affiliations
Review

Environmental Exposures and Kidney Disease

Abhijit V Kshirsagar et al. Kidney360. .

Abstract

Accumulating evidence underscores the large role played by the environment in the health of communities and individuals. We review the currently known contribution of environmental exposures and pollutants on kidney disease and its associated morbidity. We review air pollutants, such as particulate matter; water pollutants, such as trace elements, per- and polyfluoroalkyl substances, and pesticides; and extreme weather events and natural disasters. We also discuss gaps in the evidence that presently relies heavily on observational studies and animal models, and propose using recently developed analytic methods to help bridge the gaps. With the expected increase in the intensity and frequency of many environmental exposures in the decades to come, an improved understanding of their potential effect on kidney disease is crucial to mitigate potential morbidity and mortality.

Keywords: air pollution; clinical nephrology; extreme weather events; kidney disease; water pollution.

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Conflict of interest statement

N. Franceschini reports serving on the editorial boards of American Journal of Physiology–Renal Physiology and Contemporary Clinical Trials; and serving in an advisory or leadership role as a convener for the National Heart, Lung, and Blood Institute TOPMed kidney working group, as vice-chair of the Women’s Health Initiative Ancillary Committee, and on the Women’s Health Initiative Publication and Presentation Committee. A.V. Kshirsagar reports having consultancy agreements with Alkahest, Rockwell, and Target RWE; serving on the editorial boards of American Journal of Kidney Disease and Kidney Medicine; and having royalties with UpToDate (as contributor). E.M. Zeitler reports receiving research funding, via spouse, from Dexcom, Novo Nordisk, Rhythm Pharmaceuticals, and VTV Therapeutics. All remaining authors have nothing to disclose.

Figures

Figure 1.
Figure 1.
Multiple routes of environmental exposures and their potential end-organ effects. Environmental exposures occur through a variety of routes that can directly and indirectly influence kidney health. Pollutants in the air, water, and soil may be ingested, inhaled, or absorbed through the skin. To varying degrees, these pollutants cross into the bloodstream, where they may travel to, and directly injure, the kidneys. Some compounds will first be absorbed via the gastrointestinal tract, undergoing first-pass metabolism in the liver before returning to the bloodstream. Some exposures may also indirectly contribute to kidney disease by causing conditions such as diabetes and hypertension—well-established risk factors for incident or progressive CKD. DM, diabetes mellitus.
Figure 2.
Figure 2.
Integration of epidemiologic data with metabolomic/proteomic analyses to bridge the information gap. Integrating large datasets from previously disparate fields, such as epidemiology and metabolomics, may be key to connecting environmental exposures to biologic outcomes. In the proposed framework, epidemiologic data contribute to epigenome-wide association studies (EWAS), which identify putative disease-associated exposures. Concurrently, metabolomic and proteomic studies can identify signals in biologic samples that are associated with exposure to pollutants, are predictors of outcome, or both. Exposures identified via EWAS can then be compared with these signals, and candidate compounds tested in preclinical models to confirm causality.
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