Kidney development represents one of the earliest yet sustained developmental processes occurring in utero and in early childhood. Although nephrogenesis continues for up to 35 weeks’ gestation, the final processes of maturation, including renal vascular development and glomerular filtration, can continue until nearly 2 years of age (1). Disruption to these critical periods of kidney development has been linked to reduced kidney mass and nephron number in adulthood and the subsequent development of chronic illnesses including hypertension and chronic kidney disease (CKD) (1). CKD and hypertension are responsible for an estimated 5 to 11 million deaths annually, although the downstream metabolic consequences of these diseases, including the development of cardiovascular disease, further highlight the global impact they have on morbidity and mortality (2–4).
In recent years, the association between perinatal environmental exposures and an increased risk for developing adult diseases has garnered growing attention. Numerous studies have highlighted the mechanisms through which exposure to pollutants, such as heavy metals, endocrine disruptors, and air pollutants, during the perinatal period may predispose fetuses and young children toward later developing CKD and/or hypertension (Table) (5). These exposures are increasingly recognized as harmful yet potentially modifiable risk factors for the development of these diseases and may be important targets for future research and legislation.
Common toxins, effects, and sources of perinatal exposures on kidney function and development
In utero, the developing fetus is reliant on the transplacental exchange of nutrients and waste products to maintain appropriate homeostasis. Although this is a highly efficient process, maternal exposures to specific environmental chemicals may subsequently expose developing fetuses to potent nephrotoxins. This can lead to a cascade of structural and functional alterations leading to glomerular hypertrophy, increased apoptosis leading to fibrosis and tubular injury, oxidative stress, and disruption of signalling pathways including the renin-angiotensin system and aryl hydrocarbon receptor pathway (5).
Air pollutants, including fine particulate matter, ozone, and polycyclic aromatic hydrocarbons, are ubiquitous, particularly in urban areas, and have been frequently linked to poor kidney outcomes including CKD and hypertension (6). Maternal exposures during the second and third trimesters to such pollutants have been associated with hypertension in infancy and early childhood, with sustained increases persisting into late childhood (7–9).
Heavy metals are another class of environmental toxins linked to nephrotoxicity and hypertension in children. For example, lead exposure, even at low levels, during pregnancy has been associated with increased systolic blood pressure in early childhood, particularly among infants born prematurely (<37 weeks’ gestational age), in whom nephrogenesis is already disrupted (10). Cadmium is another metal that has nephrotoxic properties and has been associated with worsening markers of kidney injury with cumulative exposure (11).
Finally, endocrine disruptors, such as bisphenol A and phthalates, are another significant category of environmental toxins that have been postulated to affect risk of developing kidney diseases, although few studies have examined the effects of maternal exposures on childhood risk of CKD or hypertension, and this remains an area of research needing further exploration (6).
Implications of these findings extend beyond individual health outcomes and represent significant challenges for health care systems globally. In the United States, the total direct medical cost of CKD is projected to triple to $818 billion per year, with similar trends expected globally (12, 13). Addressing this issue requires a multifaceted approach guided by research initiatives and legislation. Research in this field is still relatively new, and only a limited number of environmental chemical classes have been investigated (6). Further research in this area needs to be supported that focuses on the independent effects of perinatal exposures to environmental chemicals on childhood outcomes, including particular attention to time- and dose-dependent effects of specific stressors (5). In addition, stricter regulations on the use of harmful chemicals and pollutants and increased public awareness and education, including careful product labeling practices, need to be prioritized in high-risk environments, such as urban city centers and commercial and industrial areas.
The link between perinatal exposure to environmental toxins and the risk of hypertension and kidney diseases highlights a pressing public health issue. By advocating for stricter regulations, promoting awareness, and investing in research, we can mitigate the silent threat posed by these insidious toxins.
Footnotes
References
- 1.↑
Sanders AP, et al. Perinatal and childhood exposure to environmental chemicals and blood pressure in children: A review of literature 2007–2017. Pediatr Res 2018; 84:165–180. doi: 10.1038/s41390-018-0055-3
- 2.↑
Luyckx VA, et al. The global burden of kidney disease and the sustainable development goals. Bull World Health Organ 2018; 96:414–422C. doi: 10.2471/BLT.17.206441
- 3.
Zhou B, et al. Global epidemiology, health burden and effective interventions for elevated blood pressure and hypertension. Nat Rev Cardiol 2021; 18:785–802. doi: 10.1038/s41569-021-00559-8
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Landsberg L, et al. Obesity‐related hypertension: Pathogenesis, cardiovascular risk, and treatment: A position paper of The Obesity Society and the American Society of Hypertension. J Clin Hypertens (Greenwich) 2012; 15:14–33. doi: 10.1111/jch.12049
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Oulerich Z, Sferruzzi-Perri AN. Early-life exposures and long-term health: Adverse gestational environments and the programming of offspring renal and vascular disease. Am J Physiol Renal Physiol 2024; 327:F21–F36. doi: 10.1152/ajprenal.00383.2023
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Hsu C-N, Tain Y-L. Adverse impact of environmental chemicals on developmental origins of kidney disease and hypertension. Front Endocrinol (Lausanne) 2021; 12:745716. doi: 10.3389/fendo.2021.745716
- 7.↑
Rosa MJ, et al. Identifying critical windows of prenatal particulate matter (PM2.5) exposure and early childhood blood pressure. Environ Res 2020; 182:109073. doi: 10.1016/j.envres.2019.109073
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Zhang M, et al. Maternal exposure to ambient particulate matter ≤2.5 µm during pregnancy and the risk for high blood pressure in childhood. Hypertension 2018; 72:194–201. doi: 10.1161/HYPERTENSIONAHA.117.10944
- 9.↑
van Rossem L, et al. Prenatal air pollution exposure and newborn blood pressure. Environ Health Perspect 2015; 123:353–359. doi: 10.1289/ehp.1307419
- 10.↑
Sanders AP, et al. Prenatal lead exposure modifies the effect of shorter gestation on increased blood pressure in children. Environ Int 2018; 120:464–471. doi: 10.1016/j.envint.2018.08.038
- 11.↑
Rodríguez-López E, et al. Early-life dietary cadmium exposure and kidney function in 9-year-old children from the PROGRESS cohort. Toxics 2020; 8:83. doi: 10.3390/toxics8040083
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Chadban S, et al. Projecting the economic burden of chronic kidney disease at the patient level (Inside CKD): A microsimulation modelling study. EClinicalMedicine 2024; 72:102615. doi: 10.1016/j.eclinm.2024.102615
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Heidenreich PA, et al. Forecasting the future of cardiovascular disease in the United States. Circulation 2011; 123:933–944. doi: 10.1161/CIR.0b013e31820a55f5
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Government of Canada. Perfluorooctane sulfonate (PFOS), its salts and precursors—information sheet. Accessed June 30, 2024. https://www.canada.ca/en/health-canada/services/chemical-substances/fact-sheets/chemicals-glance/perfluorooctane-sulfonate-public-summary.html
