The utility of urinary biomarker panel in predicting renal pathology and treatment response in Chinese lupus nephritis patients

Abstract

Given the urgent need for non-invasive biomarkers of LN, we aim to identify novel urinary biomarkers that facilitate diagnosis, assessment of disease activity and prediction of treatment response in a retrospective SLE cohort. A total of 154 SLE patients and 55 healthy controls were enrolled, among whom 73 were active LN patients. We measured renal activity by renal SLEDAI. The treatment response of the active LN patients who finished 6-month induction therapy was assessed based on the American College of Rheumatology response criteria. The expression levels of 10 urinary biomarkers (UBMs): β2-MG, calbindin D, cystatin C, IL-18, KIM-1, MCP-1, nephrin, NGAL, VCAM-1, and VDBP were tested using Luminex high-throughput proteomics technology. All but urinary nephrin levels were significantly increased in active LN compared to healthy controls. uCystatinC, uMCP-1, uKIM-1 levels were significantly higher in active LN group compared to inactive LN group. Correlation analysis revealed positive correlation between uCystatinC, uKIM-1, uMCP-1, uNGAL, uVDBP and RSLEDAI score. In renal pathology, uCystatinC, uKIM-1, uVCAM-1, and uVDBP positively correlated with activity index (AI) while uVCAM-1 positively correlated with chronicity index (CI). Moreover, the combination of uVCAM-1, uCystatinC, uKIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69–0.90). Most importantly, baseline uNGAL demonstrated good prediction ability to discriminate responders from non-responders in active LN patients after 6-month induction therapy. Using a multiplex bead technique, we have identified the combination of uVCAM-1, uCystatinC, uKIM-1 as a biomarker panel to reflect renal pathology and NGAL as a promising urinary biomarker to both reflect disease activity and predict treatment response.

Identification and Validation of a Urinary Biomarker Panel to Accurately Diagnose and Predict Response to Therapy in Lupus Nephritis

“…These results are not surprising considering that the pathogenic role of all 4 biomarkers is more in keeping with proliferative LN. In addition, we and other groups have shown that all 4 analytes correlate with the activity index in the kidney biopsy ( 16 , 29 , 30 ). A strength of our study is that we validated the proposed biomarkers in three independent cohorts and by 2 different methods of detection, demonstrating the reproducibility of their discriminatory and predictive abilities.…”

“…All 4 biomarkers, Adiponectin, MCP-1, sVCAM-1 and PF4, have been previously proposed by our group and others as potential biomarkers for ALN ( 15 – 24 ). In addition, prior studies have shown that all 4 analytes correlate with the activity index in the kidney biopsy ( 16 , 29 , 30 ), suggesting that they play a role in LN pathogenesis.…”

“…Serum and urinary levels of sVCAM-1, a surrogate marker for endothelial expression of VCAM and endothelial activation ( 46 , 47 ), have been shown to be elevated in SLE and to correlate with overall disease activity and the presence and severity of LN ( 29 , 30 , 48 – 51 ). sVCAM-1 can also serve as a chemotactic stimulus for monocytes ( 52 ) and T lymphocytes ( 53 ).…”

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

“…The combination of IgG autoantibodies against heparan sulphate, histone H2B, and vimentin could differentiate NPSLE from non-NPSLE with an AUC of 0.845 ( 86 ). The combination of urinary VCAM-1, CystatinC, and KIM-1 discriminated proliferative LN from membranous LN with an AUC of 0.80 (95%CI: 0.69–0.90) ( 161 ). A combination of five urinary proteins, namely L-PGDS, transferrin, ceruloplasmin, MCP-1, and sVCAM-1 was a good predictor of active LN (AUC= 0.898).A combined model of L-PGDS, transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC = 0.818) ( 162 ).…”

Research progress of risk factors and early diagnostic biomarkers of gout-induced renal injury

“…The IL-1 family consists of 11 members containing the IL-1 consensus sequence A-X-D, where A is an aliphatic amino acid, X is an arbitrary amino acid, and D is an aspartic acid ( 85 ). It has been shown that IL-18 is of great significance in the early diagnosis of diabetic nephropathy ( 86 ) and lupus nephritis ( 87 ). Although IL-1β has a known critical role in gout, increasing evidence suggests that other IL-1 family members are also involved in the pathogenesis of hyperuricemia and gout flares ( 88 ).…”