Association of noninvasively measured renal protein biomarkers with histologic features of lupus nephritis

Authors

  • Hermine I. Brunner,

    Corresponding author
    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    • Cincinnati Children's Hospital Medical Center, William Rowe Division of Rheumatology, E 4010, 3333 Burnet Avenue, Cincinnati, OH 45229-3039
    Search for more papers by this author
    • Drs. Brunner and Devarajan are coinventors on patents covering biomarker panels for the diagnosis of lupus nephritis.

  • Michael R. Bennett,

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • Rina Mina,

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • Michiko Suzuki,

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • Michelle Petri,

    1. Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for more papers by this author
  • Adnan N. Kiani,

    1. Johns Hopkins University School of Medicine, Baltimore, Maryland
    Search for more papers by this author
  • Joshua Pendl,

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • David Witte,

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • Jun Ying,

    1. University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
  • Brad H. Rovin,

    1. The Ohio State University, Columbus
    Search for more papers by this author
  • Prasad Devarajan

    1. Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, Ohio
    Search for more papers by this author
    • Drs. Brunner and Devarajan are coinventors on patents covering biomarker panels for the diagnosis of lupus nephritis.

    • Dr. Devarajan has received consulting fees, speaking fees, and/or honoraria from Abbott Diagnostics and Alere (less than $10,000 each) and is a coinventor on patent applications for the use of neutrophil gelatinase–associated lipocalin as a biomarker for acute kidney injury.


Abstract

Objective

To investigate the relationship of urinary biomarkers and established measures of renal function to histologic findings in lupus nephritis (LN), and to test whether certain combinations of the above-mentioned laboratory measures are diagnostic for specific histologic features of LN.

Methods

Urine samples from 76 patients were collected within 2 months of kidney biopsy and assayed for the urinary biomarkers lipocalin-like prostaglandin D synthase (L-PGDS), α1-acid glycoprotein (AAG), transferrin (TF), ceruloplasmin (CP), neutrophil gelatinase–associated lipocalin (NGAL), and monocyte chemotactic protein 1 (MCP-1). Using nonparametric analyses, levels of urinary biomarkers and established markers of renal function were compared with histologic features seen in LN, i.e., mesangial expansion, capillary proliferation, crescent formation, necrosis, wire loops, fibrosis, tubular atrophy, and epimembranous deposits. The area under the receiver operating characteristic curve (AUC) was calculated to predict LN activity, chronicity, or membranous LN.

Results

There was a differential increase in levels of urinary biomarkers that formed a pattern reflective of specific histologic features seen in active LN. The combination of MCP-1, AAG, and CP levels plus protein:creatinine ratio was excellent in predicting LN activity (AUC 0.85). NGAL together with creatinine clearance plus MCP-1 was an excellent diagnostic test for LN chronicity (AUC 0.83), and the combination of MCP-1, AAG, TF, and creatinine clearance plus C4 was a good diagnostic test for membranous LN (AUC 0.75).

Conclusion

Specific urinary biomarkers are associated with specific tissue changes observed in conjunction with LN activity and chronicity. Especially in combination with select established markers of renal function, urinary biomarkers are well-suited for use in noninvasive measurement of LN activity, LN chronicity, and the presence of membranous LN.

Ancillary