On this world kidney day we highlight two important research themes within ACS, linking environmental health and lifestyle to kidney function and cardiovascular health. PhD candidate Jonathan Overeem and physician-researcher Britt Wever talk about their research.
Vulnerability before birth
Kidney disease and hypertension can be programmed during gestation when nephrogenesis takes place. Because no new nephrons are formed after birth, environmental exposures during this window can have long-term consequences for kidney function and blood pressure regulation.
Effect of air pollution
Air pollution is a major environmental health risk, and one of its most harmful components is fine particulate matter (PM2.5). “These particles are small enough to cross biological barriers”, explains Jonathan Overeem. This includes the placenta, and the particles have been detected on the foetal side of the placenta and in foetal tissues. Because of their filtration function, the kidneys are particularly susceptible to particle accumulation. Overeem further explains, “This means that the adverse effects of PM2.5 extend beyond the lungs.” “We therefore hypothesized that maternal exposure to PM2.5 during pregnancy could impair nephrogenesis and program alterations in offspring sodium handling, kidney function, and blood pressure regulation", says Overeem.
Collaboration with the University of São Paulo
In his project, funded by the ACS Work Visit grant, Overeem went to the University of São Paulo to investigate the effects of gestational PM2.5 exposure. “In São Paulo, urban levels PM2.5 far exceed the WHO annual average of 10 µg/m³, so we could use the natural environment as intervention, and compare it to clean, filtered air”, explains Overeem. This environment accurately recapitulates the daily exposure of the population, making the findings highly translatable on a population level.
Clinical implications for kidney diseases
Most of the data associating hypertension and chronic kidney disease incidence (CKD) with PM2.5 exposure comes from observational data. “Our collaboration is the first exposome study linking PM2.5 with developmental programming of hypertension and chronic kidney disease”, notes Overeem. By identifying a new risk factor for disease programming we aim to gain new insights on why certain patients develop CKD and hypertension.
High salt intake
The incidence of diabetes and diabetic kidney disease is rising worldwide, driven in part by sedentary lifestyles and diets rich in highly processed foods that are high in salt. High salt intake is strongly linked to hypertension and cardiovascular risk, and many individuals with type 2 diabetes are salt sensitive, meaning that higher salt intake can raise blood pressure.
Effect on kidney function
“At our department, we conduct several studies on how salt intake affects kidney function in people with type 2 diabetes treated with diabetes medication”, says Britt Wever. “We compare renal salt excretion after an oral versus intravenous sodium load”, explains Wever. This way they can assess whether the gut-kidney signaling that accelerates sodium excretion after an oral sodium load in healthy individuals is equally effective in individuals with type 2 diabetes. In this study, they also investigate whether GLP-1 agonism can enhance renal sodium excretion.
Optimize treatment responses
Wever further explains, “In another study, we investigate whether the blood pressure-lowering effect of an SGLT2 inhibitor differs between a WHO-recommended salt intake (5 g/day) and a high-salt intake (14.5 g/day)”. By examining the physiological mechanisms of salt handling and the interaction with diabetes medications such as GLP-1 agonists and SGLT2 inhibitors, they hope to identify mechanisms that could optimize treatment responses. Together, these studies aim to improve our understanding of how salt intake influences kidney function and blood pressure regulation in people with type 2 diabetes.
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