Towards the most accurate diagnosis and monitoring of Complement-mediated Rare kidney diseases

Complement-mediated kidney diseases are ultra-rare conditions associated with genetic variants or circulating auto-antibodies, allowing uncontrolled complement activation, and resulting in complement deposition in the kidneys. This leads to renal inflammation and ultimately renal failure that can recur after renal transplantation.

Here we will investigate two rare kidney diseases, atypical hemolytic uremic syndrome and C3 glomerulopathy. In both there is an unmet need for accurate and standardized testing of complement abnormalities.

We aim to determine appropriate biomarkers in the circulation and tissue for diagnosis using patient blood samples, DNA, blood cell-derived endothelial cells, extracellular vesicles, and kidney biopsies.

We will apply advanced state-of-the-art methodology for the development of diagnostic assays and standardize immunological detection assays with large patient cohorts.

The phenotype of patient genetic variants will be assessed using novel assays and we will explore new pathways of complement activation.

The scientific consortium, from 6 European countries, including an early career scientist, combines expertise in adult and pediatric nephrology, immunology, genetics, basic and translational research and is associated with a SME in the field of complement and patient organizations.

The findings generated here will provide better diagnostics, disease biomarkers, stratify genetic variants and offer a better understanding of disease pathophysiology.