A new map of the human kidney has revealed a previously unrecognized form of diabetic kidney disease, defined by clusters of immune cells that drive faster progression to kidney failure.
Key Findings
- Researchers at the Perelman School of Medicine at the University of Pennsylvania published a new map of the human kidney in Nature.
- The map revealed a previously unrecognized form of diabetic kidney disease (DKD) characterized by clusters of B cells, an immune cell type.
- Patients with B cell clusters experienced faster progression to kidney failure.
Background
Diabetic kidney disease affects 20%–40% of people with diabetes and is a leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD). The global prevalence of chronic type 2 DKD exceeded 107 million in 2021, an 85% increase since 1990.
Current diagnostic methods rely on kidney function and urine protein levels, which do not explain variability in disease progression.
Methodology and Findings
The team used spatial gene activity analysis on kidney tissue samples from dozens of patients, examining over five million cells. They identified tissue patterns associated with scarring and inflammation that became more common as disease worsened.
In some patients, B cells formed organized clusters resembling structures seen in autoimmune diseases, along with supporting immune cells.
The researchers developed a gene signature and a blood test to identify this high-risk form of DKD without detailed tissue mapping.
Statements
"Diabetic kidney disease has often been treated as a single condition, but patients can have very different outcomes. By looking directly at the kidney tissue, we can now see different disease processes and start to match treatments to what's actually happening in each patient." — Katalin Susztak, MD, PhD, senior author
"Understanding how inflammation is organized within the kidney gives us a new way to classify disease. This could lead to more precise treatments tailored to each patient." — Bernhard Dumoulin, MD, first author
Funding
The study was funded in part by the National Institute of Diabetes and Digestive and Kidney Diseases and the Colton Center for Autoimmunity.