This project is focused on development of a novel biomarker test in the diagnosis and monitoring of crescentic glomerulonephritis (CGN), a severe form of inflammatory kidney injury. This test relies upon identification of a single protein in the urine: soluble CD163. This is shed from activated macrophages, the predominant cell in glomerular crescents, which are in direct communication with the urinary space. Extensive experimental work in our laboratory has brought this biomarker to technology readiness level 3. This project will bring it to level 7, laying the foundation for a definitive trial.
The first of four work packages will lay the groundwork by establishing the assay on a more sensitive electrochemiluminescence platform in the clinical laboratory of St James’s Hospital and optimising this for ISO15189 accreditation. Work package two will investigate whether the urine sCD163 level can distinguish a renal vasculitis flare from other causes of clinical deterioration in patients with known ANCA vasculitis, the main cause of CGN. We will achieve this by sampling patients with possible flare across seven sites in Ireland. Work package three will assess whether the urine sCD163 level is elevated in a wide range of potential clinical “mimics”, which have the potential for introducing a false positive test. Additionally, it will investigate whether other forms of active CGN, such as lupus nephritis, produce a similar urinary sCD163 signal. We will achieve this by engaging with four major international biobanks. The final work package will track urinary sCD163 during induction treatment for CGN to investigate its utility as a biomarker to guide timing of switch to maintenance therapy.
Most current biomarker programmes rely upon panels of compounds. We have discovered a single protein that closely mirrors CGN, which has the potential to avoid the need for kidney biopsy when this condition is suspected.
