Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios

• Published in: PloS one Vol. 17; no. 3; p. e0263778
• Main Authors: Ngamjanyaporn, Pintip, Worawichawong, Suchin, Pisitkun, Prapaporn, Khiewngam, Khantong, Kantachuvesiri, Surasak, Nongnuch, Arkom, Assanatham, Montira, Sathirapongsasuti, Nuankanya, Kitiyakara, Chagriya
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.03.2022; Public Library of Science (PLoS)
• Subjects: Analysis; Autoimmune diseases; Biology and Life Sciences; Biomarkers; Biomarkers - urine; Care and treatment; Chemokine CCL2 - urine; Chronic conditions; Correlation; Cross-Sectional Studies; Cytokines; Damage; Diagnosis; Drug dosages; Epidermal growth factor; Epidermal Growth Factor - urine; Female; Glomerulonephritis; Growth factors; Histopathology; Humans; Induction therapy; Lupus; Lupus Erythematosus, Systemic - drug therapy; Lupus nephritis; Lupus Nephritis - pathology; Male; Medicine and Health Sciences; Monocyte chemoattractant protein; Monocyte chemoattractant protein 1; Monocytes; Nephritis; Observational studies; Proteins; Proteinuria; Subgroups; Systemic lupus erythematosus; Urine; Thailand; United States > US; Bangkok Thailand
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0263778

There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN. This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment. MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66-0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone. MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.