Urinary levels of ceruloplasmin and monocyte chemoattractant protein-1 correlate with extra-capillary proliferation and chronic damage in patients with lupus nephritis

Clin Rheumatol. 2021 May;40(5):1853-1859. doi: 10.1007/s10067-020-05454-0. Epub 2020 Oct 20.

Abstract

Background and aim: There are few studies of urinary biomarkers and histopathologic features in lupus nephritis (LN). The aim was to analyze the correlation between a wide panel of urinary biomarkers and serum concentrations of anti C1q antibodies with histological items of activity and chronicity on kidney biopsy in LN patients.

Methods: Patients with systemic lupus erythematosus (SLE) according to American College of Rheumatology (ACR) criteria were included. LN diagnosis was based on ACR criteria. Histologic features of activity and chronicity indices were analyzed according to the Austin classification. Serum Anti C1q levels were determined by commercial ELISA. Urinary levels of transferrin, ceruloplasmin (CP), VCAM-1, TWEAK, monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase-associated lipocalin (NGAL), and alpha-1-acid glycoprotein were measured by commercial ELISA.

Results: We included 120 SLE patients (81% female, mean age 33.1 ± 9.3 years, 59.4% Mestizo, 37.8% Afro-Latin American): 64% had LN. Kidney biopsy was performed in 55 patients, but only 37 were made in our center. Anti C1q antibodies were associated with endocapillary proliferation. In patients with cellular crescents, urinary concentrations of CP were significantly higher. In patients with a chronicity index (CI) ≥ 4, fibrous crescents, tubular atrophy, and interstitial fibrosis, urinary MCP-1 levels were higher.

Conclusions: In SLE patients, serum anti C1q antibodies and urinary CP were associated with activity on kidney biopsy and MCP-1 with chronic damage. This panel of biomarkers could be validated in larger, multi-ethnic population as a complementary tool for better stratification of LN patients. Key Points • Urinary biomarkers are complementary useful tools for the assessment of SLE patients. • Urinary levels of CP correlated with activity findings on kidney biopsy in LN patients. • Urinary levels of MCP-1 correlated with chronic damage, especially with fibrous crescents, tubular atrophy, and interstitial fibrosis.

Keywords: Activity; Anti C1q antibodies; Biomarkers; Chronicity; Kidney biopsy; Lupus nephritis; Systemic lupus erythematosus.

MeSH terms

  • Adult
  • Biomarkers
  • Cell Proliferation
  • Ceruloplasmin / urine*
  • Chemokine CCL2 / urine*
  • Female
  • Humans
  • Lupus Erythematosus, Systemic* / pathology
  • Lupus Nephritis* / pathology
  • Male
  • Young Adult

Substances

  • Biomarkers
  • CCL2 protein, human
  • Chemokine CCL2
  • Ceruloplasmin