Urinary Neuropilin-1: A Predictive Biomarker for Renal Outcome in Lupus Nephritis

Int J Mol Sci. 2019 Sep 17;20(18):4601. doi: 10.3390/ijms20184601.

Abstract

At present, Lupus Nephritis (LN) is still awaiting a biomarker to better monitor disease activity, guide clinical treatment, and predict a patient's long-term outcome. In the last decade, novel biomarkers have been identified to monitor the disease, but none have been incorporated into clinical practice. The transmembrane receptor neuropilin-1 (NRP-1) is highly expressed by mesangial cells and its genetic deletion results in proteinuric disease and glomerulosclerosis. NRP-1 is increased in kidney biopsies of LN. In this work we were interested in determining whether urinary NRP-1 levels could be a biomarker of clinical response in LN. Our results show that patients with active LN have increased levels of urinary NRP-1. When patients were divided according to clinical response, responders displayed higher urinary and tissue NRP-1 levels at the time of renal biopsy. Areas under the receiver operating characteristic curve, comparing baseline creatinine, proteinuria, urinary NRP-1, and VEGFA protein levels, showed NRP-1 to be an independent predictor for clinical response. In addition, in vitro studies suggest that NRP-1could promote renal recovery through endothelial proliferation and migration, mesangial migration and local T cell cytotoxicity. Based on these results, NRP-1 may be used as an early prognostic biomarker in LN.

Keywords: clinical responder; lupus nephritis; neuropilin-1; renal biopsy; urinary biomarker.

MeSH terms

  • Adult
  • Biomarkers*
  • Biopsy
  • Cell Movement
  • Cell Proliferation / genetics
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / genetics
  • Lupus Nephritis / metabolism*
  • Lupus Nephritis / urine
  • Male
  • Middle Aged
  • Neuropilin-1 / genetics
  • Neuropilin-1 / metabolism*
  • Patient Outcome Assessment
  • Prognosis
  • Proteinuria
  • RNA, Messenger / genetics
  • ROC Curve
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism

Substances

  • Biomarkers
  • RNA, Messenger
  • Neuropilin-1