The Associations of Plasma Biomarkers of Inflammation with Histopathologic Lesions, Kidney Disease Progression, and Mortality - The Boston Kidney Biopsy Cohort Study

Abstract Background Soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, YKL-40, monocyte chemoattractant protein (MCP)-1, and soluble urokinase plasminogen activator receptor (suPAR) have emerged as promising biomarkers of inflammation but have not been evaluated across diverse types of kidney diseases. Methods We measured these plasma biomarkers in 523 individuals enrolled into a prospective, observational cohort study of patients undergoing clinically indicated native kidney biopsy at three tertiary care hospitals. Two kidney pathologists adjudicated biopsy specimens for semiquantitative scores of histopathology. Proportional hazard models tested associations between biomarkers and risks of kidney disease progression (composite of ≥40% eGFR decline or ESKD) and death. Results Mean eGFR was 56.4±36 ml/min/1.73m2 and the median proteinuria (IQR) was 1.6 (0.4, 3.9) g/g creatinine. The most common primary clinicopathologic diagnoses were proliferative glomerulonephritis (29.2%), non-proliferative glomerulopathy (18.1%), advanced glomerulosclerosis (11.3%), and diabetic kidney disease (11.1%). sTNFR-1, sTNFR-2, MCP-1, and suPAR were associated with tubulointerstitial and glomerular lesions. YKL-40 was not associated with any histopathologic lesions after multivariable adjustment. During a median follow-up of 65 months, 182 participants suffered kidney disease progression and 85 participants died. After multivariable adjustment, each doubling of sTNFR-1, sTNFR-2, YKL-40 , and MCP-1 was associated with increased risks of kidney disease progression with hazard ratios ranging 1.21–1.47. Each doubling of sTNFR-2, YKL-40, and MCP-1 was associated with increased risks of death with hazard ratios ranging 1.33–1.45. suPAR was not significantly associated with kidney disease progression or death. Conclusions sTNFR-1, sTNFR-2, YKL-40, MCP-1, and suPAR are associated with underlying histopathologic lesions and adverse clinical outcomes across a diverse set of kidney diseases.