Rationale and design of the Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study

Clin Exp Nephrol. 2024 May;28(5):431-439. doi: 10.1007/s10157-023-02449-4. Epub 2024 Jan 25.

Abstract

Introduction: Disease subtyping and monitoring are essential for the management of nephrotic syndrome (NS). Although various biomarkers for NS have been reported, their clinical efficacy has not been comprehensively validated in adult Japanese patients.

Methods: The Japanese Biomarkers in Nephrotic Syndrome (J-MARINE) study is a nationwide, multicenter, and prospective cohort study in Japan, enrolling adult (≥18 years) patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), membranoproliferative glomerulonephritis (MPGN), C3 glomerulopathy (C3G), and lupus nephritis (LN). Baseline clinical information and plasma and urine samples will be collected at the time of immunosuppressive therapy initiation or biopsy. Follow-up data and plasma and urine samples will be collected longitudinally based on the designated protocols. Candidate biomarkers will be measured: CD80, cytotoxic T-lymphocyte antigen 4, and soluble urokinase plasminogen activator receptor for MCD and FSGS; anti-phospholipase A2 receptor and thrombospondin type-1 domain-containing protein 7A antibodies for MN; fragment Ba, C3a, factor I, and properdin for MPGN/C3G; and CD11b, CD16b, and CD163 for LN. Outcomes include complete and partial remission, relapse of proteinuria, a 30% reduction in estimated glomerular filtration rate (eGFR), eGFR decline, and initiation of renal replacement therapy. The diagnostic accuracy and predictive ability for clinical outcomes will be assessed for each biomarker.

Results: From April 2019 to April 2023, 365 patients were enrolled: 145, 21, 138, 10, and 51 cases of MCD, FSGS, MN, MPGN/C3G, and LN, respectively.

Conclusion: This study will provide valuable insights into biomarkers for NS and serve as a biorepository for future studies.

Keywords: Biomarker; Glomerular disease; Liquid biopsy; Proteinuria; Protocol.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • B7-1 Antigen*
  • Biomarkers* / blood
  • Biomarkers* / urine
  • East Asian People
  • Female
  • Glomerulonephritis, Membranoproliferative / blood
  • Glomerulonephritis, Membranoproliferative / diagnosis
  • Glomerulonephritis, Membranoproliferative / urine
  • Glomerulonephritis, Membranous / blood
  • Glomerulonephritis, Membranous / diagnosis
  • Glomerulonephritis, Membranous / urine
  • Glomerulosclerosis, Focal Segmental / blood
  • Glomerulosclerosis, Focal Segmental / diagnosis
  • Glomerulosclerosis, Focal Segmental / urine
  • Humans
  • Japan
  • Lupus Nephritis / blood
  • Lupus Nephritis / diagnosis
  • Lupus Nephritis / urine
  • Male
  • Nephrosis, Lipoid / blood
  • Nephrosis, Lipoid / diagnosis
  • Nephrosis, Lipoid / urine
  • Nephrotic Syndrome* / blood
  • Nephrotic Syndrome* / diagnosis
  • Nephrotic Syndrome* / urine
  • Prospective Studies
  • Receptors, Phospholipase A2 / immunology
  • Receptors, Urokinase Plasminogen Activator / blood
  • Research Design
  • Thrombospondins / blood

Substances

  • Biomarkers
  • Receptors, Urokinase Plasminogen Activator
  • CD80 protein, human
  • Receptors, Phospholipase A2
  • Thrombospondins
  • PLA2R1 protein, human
  • B7-1 Antigen