A panel of urinary proteins predicts active lupus nephritis and response to rituximab treatment

Rheumatology (Oxford). 2021 Aug 2;60(8):3747-3759. doi: 10.1093/rheumatology/keaa851.

Abstract

Objectives: ∼30% of patients with SLE develop LN. Presence and/or severity of LN are currently assessed by renal biopsy, but biomarkers in serum or urine samples may provide an avenue for non-invasive routine testing. We aimed to validate a urinary protein panel for its ability to predict active renal involvement in SLE.

Methods: A total of 197 SLE patients and 48 healthy controls were recruited, and urine samples collected. Seventy-five of the SLE patients had active LN and 104 had no or inactive renal disease. Concentrations of lipocalin-like prostaglandin D synthase (LPGDS), transferrin, alpha-1-acid glycoprotein (AGP-1), ceruloplasmin, monocyte chemoattractant protein 1 (MCP-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) were quantified by MILLIPLEX® Assays using the MAGPIX Luminex platform. Binary logistic regression was conducted to examine whether proteins levels associate with active renal involvement and/or response to rituximab treatment.

Results: Urine levels of transferrin (P <0.005), AGP-1 (P <0.0001), MCP-1 (P <0.001) and sVCAM-1 (P <0.005) were significantly higher in SLE patients when compared with healthy controls. Furthermore, levels of transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 (all P <0.0001) were higher in SLE patients with active LN when compared with patients without active LN. A combination of five urine proteins, namely LPGDS, transferrin, ceruloplasmin, MCP-1 and sVCAM-1 was a good predictor of active LN (AUC 0.898). A combined model of LPGDS, transferrin, AGP-1, ceruloplasmin, MCP-1 and sVCAM-1 predicted response to rituximab treatment at 12 months (AUC 0.818).

Conclusions: Findings support the use of a urinary protein panel to identify active LN and potentially predict response to treatment with rituximab in adult SLE patients. Prospective studies are required to confirm findings.

Keywords: SLE; biomarker; inflammation; lupus nephritis; renal; rituximab; stratification; treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antirheumatic Agents / therapeutic use*
  • Ceruloplasmin / urine
  • Chemokine CCL2 / urine
  • Female
  • Humans
  • Intramolecular Oxidoreductases / urine
  • Lipocalins / urine
  • Logistic Models
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / urine
  • Lupus Nephritis / drug therapy
  • Lupus Nephritis / urine*
  • Male
  • Middle Aged
  • Orosomucoid / urine
  • Prognosis
  • Rituximab / therapeutic use*
  • Transferrin / urine
  • Treatment Outcome
  • Vascular Cell Adhesion Molecule-1 / urine

Substances

  • Antirheumatic Agents
  • Chemokine CCL2
  • Lipocalins
  • Orosomucoid
  • Transferrin
  • Vascular Cell Adhesion Molecule-1
  • Rituximab
  • Ceruloplasmin
  • Intramolecular Oxidoreductases
  • prostaglandin R2 D-isomerase