Lifespan risk for cardio-kidney-metabolic diseases
Kidney health is shaped long before kidney disease becomes clinically visible. Across the lifespan, the kidneys are continuously exposed to environmental, metabolic, cardiovascular and inflammatory stressors. These chronic exposures may leave subtle but lasting biological traces, gradually increasing the risk of hypertension, chronic kidney disease, cardiovascular disease and metabolic dysfunction. Understanding these early and cumulative processes is essential if we want to move from treating established kidney disease towards preventing it.
Within Kidney Health Amsterdam UMC, the research theme Lifespan Cardio-Kidney-Metabolic Risk focuses on how long-term exposures affect kidney structure and function from early life into adulthood and ageing. The kidney is not an isolated organ. It is deeply connected to vascular health, immune regulation, metabolism and blood pressure control. Disturbances in one of these systems can influence the others, creating a complex network of cardio-kidney-metabolic risk. This theme therefore brings together expertise from nephrology and pathology to study kidney disease at multiple levels: from patients and clinical phenotypes to tissue, cells and molecular mechanisms.
A central concept in this research line is the exposome: the totality of environmental and lifestyle exposures a person encounters throughout life. These exposures include air pollution, diet, salt intake, metabolic stress, inflammation, medication, infections, socioeconomic circumstances and other chronic environmental influences. While a single exposure may appear modest, repeated or combined exposures over time may contribute to vascular dysfunction, immune activation, accelerated renal ageing and loss of kidney resilience. In this way, chronic exposure can quietly shape future kidney risk.
This research theme aims to understand how such exposures interact with biological susceptibility. Some individuals may be more vulnerable to environmental stressors because of genetic background, developmental factors, pre-existing kidney injury or impaired vascular adaptation. By studying these interactions, we can better understand why certain people develop salt-sensitive hypertension, chronic kidney disease or cardio-metabolic complications, while others remain relatively protected.
“Kidney injury takes place before diagnosis; by examining the exposome we get a more holistic view of vulnerable patient populations”
An important part of this work focuses on salt-sensitive hypertension, a condition in which blood pressure rises in response to increased salt intake. Salt sensitivity is highly relevant to kidney health because the kidney plays a key role in sodium handling, extracellular volume regulation and long-term blood pressure control. Impaired renal sodium excretion, vascular stiffness, immune activation and tissue inflammation may all contribute to this phenotype. Understanding salt sensitivity may therefore reveal early mechanisms linking lifestyle exposures to hypertension and kidney damage.
Within this theme, ongoing research includes a human salt intervention study investigating how low- and high-salt diets influence immune and vascular pathways in healthy individuals and people with kidney disease. This study provides a controlled way to examine how dietary salt affects blood pressure regulation, immune cell activation and markers of kidney and cardiovascular risk. By connecting clinical responses to cellular and molecular readouts, the study helps identify mechanisms that may explain why some individuals are more salt-sensitive than others.
In parallel, experimental work in Brazil investigates the impact of air pollution, particularly fine particulate matter known as PM2.5, on kidney and cardiovascular vulnerability. This animal study explores how exposure to PM2.5 may influence kidney development, vascular function and susceptibility to later-life stressors such as high salt intake. Air pollution is increasingly recognized as an important contributor to cardio-kidney-metabolic disease, yet the underlying kidney-specific mechanisms remain incompletely understood. By combining environmental exposure models with renal and vascular outcomes, this work helps clarify how polluted air may become a silent driver of kidney risk.
The overlap between nephrology and pathology is essential for this research. Nephrology provides the clinical framework: blood pressure, kidney function, sodium handling, cardiovascular risk and patient phenotypes. Pathology allows us to look deeper into the tissue itself, identifying structural injury, inflammation, fibrosis, vascular changes and cellular adaptation. Together, these disciplines create a translational bridge between exposure, mechanism and disease.
Ultimately, the goal of this research theme is to identify early pathways of kidney vulnerability before irreversible damage occurs. By studying how chronic exposures accumulate across the lifespan, Kidney Health Amsterdam UMC aims to improve prevention, refine risk stratification and develop more personalized strategies for protecting kidney and cardiovascular health. This approach recognizes that kidney disease is not only the result of what happens at the moment of diagnosis, but also of the biological history written over many years of exposure, adaptation and resilience.
