Urinary MCP-1 and TWEAK as non-invasive markers of disease activity and treatment response in patients with lupus nephritis in South Africa

Abstract

Background: Treatment of patients with lupus nephritis (LN) requires judicious use of immunosuppression. Novel biomarkers may be useful for monitoring disease activity and treatment response. We assessed the utility of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary tumour necrosis factor-like weak inducer of apoptosis (uTWEAK) for disease activity and treatment response monitoring in South Africans with LN. Methods: We recruited consenting patients with active LN confirmed on kidney biopsy. Urinary levels of MCP-1 and TWEAK were assayed at baseline and after completion of induction therapy using ELISA methods. We also collected relevant demographic, clinical and biochemical data for patients included in this study. Results: The mean age of patients in this study was 29.8 ± 10.7 years, 60% were patients of mixed ancestry, 70% had proliferative LN and mean spot urine proteinuria at baseline was 0.37 (0.18-0.59) g/mmolCr. At completion of induction therapy, the level of uMCP-1 had reduced to 314.5 (IQR: 197.0 – 622) pg/mgCr from a baseline of 1092.7 (IQR: 578.6-1848) pg/mgCr (P=0.06) while uTWEAK had reduced to 36.0 (IQR: 17.0-88.0) pg/mgCr from 159.0 (IQR: 88.5-295.5) pg/mgCr (P=0.03). For patients reaching early complete or partial remission, both biomarkers had significantly declined in their urine: uMCP-1 (p=0.018) and uTWEAK (p=0.015). There was no reduction of both biomarkers in patients not achieving remission and no association between uMCP-1 or uTWEAK with renal histological features. Conclusion: Our study shows that uMCP-1 and uTWEAK are elevated in patients with active LN, correlated with the remission status (response to treatment) at the end of induction therapy and can therefore be useful for monitoring disease activity and treatment response.