New molecular atlas offers unprecedented insight into human kidney function

The kidney, a critical organ for waste filtration and fluid regulation, is the subject of a groundbreaking molecular mapping project that could reshape our understanding of renal health. Despite advances in transcriptomics and proteomics, lipids-key structural and signaling molecules-have remained relatively unexplored in the context of kidney function. That is now changing thanks to a new study published in Science Advances by researchers from the Mass Spectrometry Research Center and the lab of Jeff Spraggins at Vanderbilt University and Raf Van de Plas' group at Delft University of Technology. In the new paper, the team created a high-resolution molecular atlas of the human kidney, leveraging a cutting-edge imaging mass spect technique called MALDI and interpretable machine learning.

This atlas is the most comprehensive of its kind, incorporating data from 29 human kidney donors. The researchers mapped lipid species across millions of mass spect measurements from more than 100,000 discrete functional tissue units, including glomeruli, proximal and distal tubules, thick ascending limbs, and collecting ducts.

This work has been our most ambitious and comprehensive multimodal molecular imaging study to date. By spatially linking lipid composition to anatomical and functional regions of the kidney, we were able to effectively generate a molecular bar code for each component of the human nephron."

Jeff Spraggins, senior author and co-lead of the project

Among the striking findings: The atlas' molecular view of kidney function reveals spatially specific lipid biomarkers for distinct functional tissue units of the nephron. Despite the natural differences between human donors, specific sphingomyelins-a type of lipid-were consistently enriched in glomeruli, suggesting a role in supporting cell types critical for filtration. Other lipid classes, including sulfatides and phosphatidylserines, were strongly associated with nutrient reabsorption and ion transport in structures such as the loop of Henle and proximal tubules.

The team also explored how lipid profiles vary by sex and body mass index. Leveraging interpretable machine learning models, the team identified candidate biomarkers, including arachidonic acid–containing phospholipids, that may reflect sex-specific physiology and hormonal regulation. Additionally, distinct phosphatidylcholines and sphingomyelins were associated with obesity-linked alterations in kidney tissue, including markers of glomerular sclerosis.

"It's like giving everyone a Google Maps of the kidney, but instead of streets and landmarks, we're mapping cellular organization and molecular signatures," Spraggins said. "And just like maps, once you can see the terrain, you can start navigating and intervening with more precision."

The potential benefits are broad: an improved understanding of the relationships between cellular and molecular distributions of the kidney, more precise stratification of patient disease risk based on molecular data, and eventually, lipid-targeted interventions for diseases.

Critically, the dataset and tools are available for free via the National Institutes of Health's Human Biomolecular Atlas Program, which is commonly referred to as HuBMAP, which means that the broader research community can mine this resource for new hypotheses. The Biomolecular Multimodal Imaging Center, the NIH-funded HuBMAP tissue mapping center located at Vanderbilt University and led by Spraggins, has been focused on developing an atlas for the human kidney and other organ systems for six years. In addition to Vanderbilt researchers, BIOMIC also comprises clinicians from Vanderbilt University Medical Center and data scientists from Delft University of Technology in the Netherlands.

The study's insights could translate into new diagnostic markers or therapeutic targets for kidney-related diseases. "This atlas establishes a molecular baseline," Melissa Farrow, co-first author and research associate professor of cell and developmental biology, said. "By comparing diseased tissue to this reference, we can begin to pinpoint lipid perturbations that underlie pathology."

Ultimately, this project marks a pivotal step toward integrating lipidomics into the biomedical mainstream and redefines how we look at organs through a molecular lens.