Longitudinal serum proteomics identifies inflammatory and metabolic pathways in hypertensive nephrosclerosis progression.

BACKGROUND: Hypertensive nephrosclerosis (HN) is a major cause of end-stage renal disease; however, few longitudinal studies have employed serum proteomics to document its progression. This study aimed to identify potential circulating biomarkers indicative of disease progression in HN by performing serum proteomic analysis at two time points in patients with progressive and stable disease. METHODS: Forty-one patients diagnosed with HN were recruited from the UK Salford Kidney Study, with serum samples collected at baseline and follow-up (1.5-10 years after baseline). Twenty-five patients experienced stable disease course, while 16 patients experienced progressive disease. Proteomics was performed via tandem mass tag labelling and liquid chromatography-tandem mass-spectrometry (LC-MS). Pathway analysis was performed on all significantly abundant proteins, as was network analysis of circulating proteins that are abundant in the kidney according to the Human Protein Atlas. RESULTS: Pathway analysis revealed significant enrichment in pathways related to inflammation and infection, including complement and coagulation cascades, as well as metabolic processes in patients with disease progression. Marker abundance levels related to adhesion and the ECM were also altered in progresssive disease follow-up, compared to stable disease follow-up. CONCLUSION: The observed changes in inflammatory and adhesion-related pathways may offer valuable insights into the mechanisms driving HN progression and potential targets for intervention.