Adverse Impact of Environmental Chemicals on Developmental Origins of Kidney Disease and Hypertension

Abstract

Chronic kidney disease (CKD) and hypertension are becoming a global health challenge, despite developments in pharmacotherapy. Both diseases can begin in early life by so-called "developmental origins of health and disease" (DOHaD). Environmental chemical exposure during pregnancy can affect kidney development, resulting in renal programming. Here, we focus on environmental chemicals that pregnant mothers are likely to be exposed, including dioxins, bisphenol A (BPA), phthalates, per- and polyfluoroalkyl substances (PFAS), polycyclic aromatic hydrocarbons (PAH), heavy metals, and air pollution. We summarize current human evidence and animal models that supports the link between prenatal exposure to environmental chemicals and developmental origins of kidney disease and hypertension, with an emphasis on common mechanisms. These include oxidative stress, renin-angiotensin system, reduced nephron numbers, and aryl hydrocarbon receptor signaling pathway. Urgent action is required to identify toxic chemicals in the environment, avoid harmful chemicals exposure during pregnancy and lactation, and continue to discover other potentially harmful chemicals. Innovation is also needed to identify kidney disease and hypertension in the earliest stage, as well as translating effective reprogramming interventions from animal studies into clinical practice. Toward DOHaD approach, prohibiting toxic chemical exposure and better understanding of underlying mechanisms, we have the potential to reduce global burden of kidney disease and hypertension.

Keywords: DOHaD (developmental origins of health and disease); chronic kidney disease; endocrine disruption chemical; environmental chemical; hypertension; oxidative stress; renin-angiotensin system.

Figure 1

Adverse impact of maternal environmental chemical exposure on developmental origins of kidney disease and hypertension. In pregnancy, exposure to various environmental chemicals occurs through daily consumer activity. There are many sources of contamination like industry, waste infrastructure, consumer products, contaminated foods, etc. These environmental chemicals cause renal programming, resulting in chronic kidney disease and hypertension in adulthood.

Figure 2

Overview of the common mechanisms of renal programming in response to various environmental chemicals in early life. RAS, renin-angiotensin system; AHR, aryl hydrocarbon receptor.