cGN is one of the most dangerous forms of kidney inflammation. Without treatment, it can lead to terminal kidney failure within a few weeks. The standard therapy to date consists of high doses of glucocorticoids (steroids), which strongly suppress the immune system. Although these drugs are effective, they are often associated with significant side effects, including diabetes, osteoporosis, and severe infections.
The team led by Professor Christian Kurts, Director of the Institute for Molecular Medicine and Experimental Immunology at the UKB and member of the ImmunoSensation² Cluster of Excellence and the Transdisciplinary Research Area (TRA) “Life and Health” at the University of Bonn, has now investigated in more detail how steroids work in the kidney – and why lower doses may achieve the same effect. Using modern single-cell and spatial gene sequencing and disease models in mice, the researchers identified a specific subgroup of pro-inflammatory neutrophils as immune cells that significantly promote kidney damage. These cells originate directly in the inflamed kidney tissue and remain active there longer than normal neutrophils.
“Our study shows that doctors do not necessarily need extremely high doses of steroids to suppress these cells – small, repeated doses may be sufficient,” explains Prof. Kurts. In the mouse model, the researchers were able to show that low, regularly administered glucocorticoids block the formation of these harmful cells – even without an initial high dose. Kidney biopsies from patients treated with low doses also showed fewer of these immune cells.
“Single-cell sequencing allowed us to track the harmful neutrophils directly in the inflamed kidney,” says Dr. Junping Yin, first author of the study and doctoral student with Prof. Kurts. “This opens up new ways to use steroids in a more targeted and safer manner.”
If the results are confirmed in clinical trials, patients could benefit in the future from safer, low-dose therapies that protect their kidneys without putting unnecessary strain on the body. In the long term, the approach could also have an impact on other autoimmune and inflammatory diseases in which steroids are currently used in high doses.