Background Kidney involvement is common in ANCA-associated vasculitis (AAV), but early detection of glomerulonephritis often presents a challenge.
Objectives We evaluated diagnostic significance of urinary levels of kidney injury molecule-1 (uKIM-1), monocyte chemoattractant protein-1 (uMCP-1) and type IV collagen (uCollagenIV) and serum levels of MCP-1 (sMCP-1) and CollagenIV (sCollagenIV) and their relationship with nephritis activity and prognosis in AAV.
Methods We enrolled 78 patients with AAV, diagnosed according to CHCC2012 definition (GPA=48, MPA=19, EGPA=11), 32 male, 46 female, aged 55 (45;61). To assess disease activity and kidney involvement we measured proteinuria, hematuria, serum creatinine (SCr), eGFR (CKD-EPI), BVAS and VDI. Urinary and serum concentrations of biomarkers were measured by ELISA.
Results 28 patients had active renal AAV (35.9%, group 1), 26 had active nonrenal AAV (33.3%, group 2) and 24 were in long-term remission (30.8%, group 3). Median urinary levels of all biomarkers in active renal AAV were significantly higher than in groups 2 and 3 (Table), and did not depend on age and nosological form of AAV. Urinary excretion of all molecules was comparable in groups 2 and 3. There was a significant difference in sMCP-1 levels only between groups 1 and 3. sCollagenIV levels were similar in all groups.
Significant positive correlations were found between urinary excretion of all biomarkers and features of nephritis activity: hematuria, proteinuria, renal component of BVAS (all p<0.05). uCollagenIV level also had a significant positive correlation with SCr and a negative correlation with eGFR (all p<0.05).
sMCP-1 level showed no association with signs of nephritis activity, but had a positive correlation with CRP and total BVAS (p<0.05). sCollagenIV level had no association with disease activity but had a correlation with SCr and eGFR (all p<0.0001).
ROC-analysis showed that uMCP-1≥159 pg/mL identified renal involvement with sensitivity 89%, specificity 67% (AUC 0.80). uKIM-1≥2283.3 pg/mL had similar sensitivity (92%) and lower specificity (58%), AUC 0.76. uCollagenIV≥3.09 mcg/L showed the worst sensitivity (57%), but the highest specificity (86%), AUC 0.76.
Conclusions Urinary excretion of all biomarkers was significantly increased in active renal vasculitis. We suggest that uKIM-1 and uMCP-1 levels reflect local renal inflammation, while elevated uCollagenIV is likely to represent both glomerular basement membrane damage and activation of renal fibrogenesis. Limited specificity or sensitivity of individual urinary biomarkes may justify their combined use to identify active renal AAV. In contrast serum MCP-1 and CollagenIV only show a weak correlation with overall inflammatory activity and kidney dysfunction respectively, but have no association with nephritis activity.
Disclosure of Interest None declared
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