ALCAM and VCAM-1 as urine biomarkers of activity and long-term renal outcome in systemic lupus erythematosus

Rheumatology (Oxford). 2020 Sep 1;59(9):2237-2249. doi: 10.1093/rheumatology/kez528.

Abstract

Objectives: We investigated the cell adhesion molecules (CAMs) Vascular CAM 1 (VCAM-1) and Activated Leucocyte CAM (ALCAM) as urinary biomarkers in SLE patients with and without renal involvement.

Methods: Female SLE patients (n = 111) and non-SLE population-based controls (n = 99) were enrolled. We measured renal activity using the renal domain of the BILAG index and urine (U) and plasma (P) concentrations of soluble (s)VCAM 1 and U-sALCAM using ELISA. U-sCAM levels were next corrected by U-creatinine.

Results: U-sVCAM-1/creatinine and U-sALCAM/creatinine ratios were higher in SLE patients vs non-SLE controls (P < 0.001 for both), as well as in patients with active/low-active (BILAG A-C; n = 11) vs quiescent (BILAG D; n = 19) LN (P = 0.023 and P = 0.001, respectively). U-sALCAM/creatinine but not U-sVCAM-1/creatinine ratios were higher in patients with nephritis history (BILAG A-D; n = 30) vs non-renal SLE (BILAG E; n = 79) (P = 0.014). Patients with baseline U-sVCAM-1/creatinine ratios ≥75th percentile showed a 23-fold increased risk of a deterioration in estimated glomerular filtration rate by ≥25% during a 10-year follow-up (odds ratio: 22.9; 95% CI: 2.8, 189.2; P = 0.004); this association remained significant after adjustments for age, disease duration and organ damage. Traditional markers including anti-dsDNA antibodies did not predict this outcome.

Conclusion: While high U-sVCAM-1 levels appear to reflect SLE disease activity, sALCAM might have particular importance in renal SLE. Both U-sVCAM-1 and U-sALCAM showed ability to distinguish SLE patients with active renal involvement from patients with quiescent or no prior nephritis. High U-sVCAM-1 levels may indicate patients at increased risk for long-term renal function loss.

Keywords: adhesion molecules; biomarkers; lupus nephritis; systemic lupus erythematosus; urinary biomarkers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / urine*
  • Biomarkers / urine
  • Case-Control Studies
  • Cell Adhesion Molecules, Neuronal / urine*
  • Creatinine / urine
  • Female
  • Fetal Proteins / urine*
  • Humans
  • Kidney / metabolism
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / urine*
  • Lupus Nephritis / etiology*
  • Middle Aged
  • Risk Factors
  • Severity of Illness Index
  • Vascular Cell Adhesion Molecule-1 / urine*

Substances

  • ALCAM protein, human
  • Antigens, CD
  • Biomarkers
  • Cell Adhesion Molecules, Neuronal
  • Fetal Proteins
  • Vascular Cell Adhesion Molecule-1
  • Creatinine