Bio: Alessandra Tammaro is a junior group leader at the department of pathology at Amsterdam UMC (NL), specializing in the biological mechanisms of premature renal aging, a key risk factor for chronic kidney disease (CKD). With CKD affecting over 850 million people globally and treatment options remaining limited, Alessandra’s research addresses critical gaps in understanding the disease and prevent chronic progression. She is leading the international PMkidney consortium (www.pmkidney.com), where she explores the biological mechanisms by which air pollution—a significant yet often overlooked risk factor for CKD—impacts on kidney health and potentially accelerates renal aging.

Abstract: Air pollution is a significant yet often overlooked factor in the development of chronic kidney disease (CKD). Limited epidemiological evidence indicates that early-life exposure to particulate matter can impair organ growth resulting in prematurity and low birth weight. These early disruptions increase the risk of hypertension and CKD in later life. Ultrafine particles (UFPs), which primarily come from transportation, are more toxic than larger particles based on mass. UFPs can cross the placenta and undergo high renal clearance, posing a significant risk to kidney development and function. This study aimed to investigate the impact of UFPs on kidney development and resilience. Pregnant mice and their offspring were exposed to carbonaceous UFPs or filtered air through inhalation. The animals were sacrificed at postnatal day 21, resulting in four groups: control, prenatal, postnatal, and pre+postnatal exposure. Kidneys were processed for histopathology, immunofluorescence targeting proximal tubule (PT) markers, transmission electron microscopy (TEM), and mitochondrial assays. Additionally, iPSCs-derived kidney organoids were exposed to Printex 90 (a proxy for UFPs), followed by hypoxia/re-oxygenation, and gene expression analysis was performed. Using a deep-learning algorithm to detect subtle morphological changes in the kidney, we observed impaired development of PT in the pre+postnatal exposure group. Further analysis with PT markers and TEM revealed a disorganized brush border and mitochondrial abnormalities in the PT. Metabolically, these changes led to reduced levels of nicotinamide adenine dinucleotide (NAD+) and a decreased mitochondrial DNA copy number. In vitro, kidney organoids exposed to UFPs and hypoxia/re-oxygenation injury showed increased PT damage marker KIM1 and decreased NAD+ levels. Prenatal exposure to rather clean UFPs triggers metabolic stress, starving PT at a critical time during development leading reduced resilience to stress, possibly enhancing the risk of CKD later in life.  This suggests that the physical nature of UFPs may be a key driver for these responses.