Novel biomarkers of crescentic glomerulonephritis identified by urinary proteomics

Crescentic glomerulonephritis (CrGN) with rapidly progressive renal function loss necessitates prompt pathology diagnosis and treatment. Non-invasive biomarkers are crucial in cases where renal biopsy is unavailable or unsuitable. Urinary proteomics, particularly data-independent acquisition (DIA) proteomics, might provide potential indicators.

We recruited crescentic nephritis proved by renal biopsy at Peking Union Medical College Hospital (PUMCH) from May 2022 to April 2023 and age-matched nephritis, acute kidney injury (AKI), and health controls. The CrGN group is the patients with extensive glomerular crescents over 50%. We performed liquid chromatography with tandem mass spectrometry analysis to identify differentially expressed proteins (DEPs), ingenuity pathway analysis (IPA), and the proteome map for significant pathways and crucial proteins among patients and controls, then validated using enzyme-linked immunosorbent assay analysis.

We enrolled a total of 137 participants, 55 in the proteomics cohort [15 CrGN (Type I: n = 1, II: n = 3, III: n = 11), 10 AKI, 15 non-crescentic nephritis, 15 healthy controls] and 82 in the validation cohort (33 CrGN, 6 AKI, 43 nephritis). Males occupied 42.3%, and the average age was 48 years of age. IPA analysis showed that neutrophil degranulation and complement cascade were the top two pathways in CrGN but not in the healthy and nephritis groups. Pathway analysis revealed activation of the neddylation pathway in CrGN compared to AKI patients. After integrating the DEPs among three groups via the Venn plot, we observed eight DEPs significantly associated with the CrGN, among which Coagulation factor V (F5), Phospholipid transfer protein (PLTP), and alcohol dehydrogenase 1C were significant proteins. The area under the curve values of F5 and PLTP in the validation cohort for predicting CrGN were 0.831 and 0.780 (P < .001).

By non-invasive urine proteomics, the new biomarkers F5/UCr and PLTP/UCr hold promise in identifying the CrGN patient.