Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease

Background: Biomarkers for non-invasive assessment of histopathology and prognosis are needed in patients with kidney disease. Methods: Using a proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semi-quantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of kidney replacement therapy) and death. Results: After multivariable adjustment and correction for multiple testing, 57 proteins were associated with different histopathologic lesions. The top performing markers positively associated with acute tubular injury and interstitial fibrosis and tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and immunoglobulin domain-containing protein 2 (VSIG2), respectively. 30 proteins were significantly associated with kidney disease progression and 35 with death. The top performing markers for kidney disease progression were placental growth factor (HR per doubling 5.4, 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (HR 2.4, 95% CI 1.8 to 3.3). Conclusion: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases.