Kidney disease signatures uncovered in large-scale cellular study

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Matthias Kretzler (reproduced with permission of Michigan MedicineUniversity of Michigan)

New research co-led by Matthias Kretzler (Michigan Medicine University of Michigan—Ann Arbor, USA) outlines the creation of a cellular atlas of the kidney describing nearly 100 cell types and states. It represents, states a press release, “the most comprehensive study of cellular states, neighbourhoods, and outcome-associated signatures in the kidney”.

Kidneys monitor and maintain the internal balance in the body, filter out waste and excess fluids in the urine, the press release goes on to note. In order to perform these functions, specialised cell types and surrounding cells (neighbourhoods) work in concert.

Researchers defined interactions within tissue neighbourhoods by studying more than 400,000 individual cells and nuclei from kidney biopsy tissue samples provided by kidney donors and patients with kidney diseases.

By comparing data from donor and disease samples, 28 cellular states were found altered in injured kidneys. Neighbourhoods were then mapped in the kidneys where these injury patterns were found.

Large-scale 3D imaging analysis of nearly 1.2 million neighbourhoods provided corresponding connections between kidney cells and active immune responses. These analyses defined the pathways relevant to injuries or predictors of a decline in kidney function and, the researchers say, establish “a rich data source for therapeutic development”.

Data sharing and visualisation tools have been developed in parallel to facilitate access for researchers around the world at KPMP.org, they add.

The study was performed by the Kidney Precision Medicine Project (KPMP), funded by the National Institute of Diabetes and Digestive and Kidney Diseases, in “close collaborations” with the Nephrotic Syndrome Study Network (NEPTUNE), the Human Cell Atlas and the Human BioMolecular Atlas Program (HubMap). NEPTUNE is part of the National Institutes of Health-funded Rare Diseases Clinical Research Network.

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