Development of a multiple urinary biomarker model to predict the tubulointerstitial fibrosis area in patients with primary IgA Nephropathy

BMC Nephrol. 2025 Mar 20;26(1):141. doi: 10.1186/s12882-025-04049-8.

Abstract

Background: Previous studies highlighted the utility of individual urinary biomarkers in the prediction of interstitial fibrosis in IgA Nephropathy patients. However, it´s uncertain which biomarker or combination of biomarkers provides a more accurate estimation of renal interstitial fibrosis Surface. Herein, we measured the urinary excretion of a set of seven tubular injury biomarkers in a group of patients with primary IgA Nephropathy and analyzed their utility as non-invasive estimators of interstitial fibrosis area found on kidney biopsy.

Methods: Two hundred forty-seven adults with primary IgA Nephropathy diagnosed by kidney biopsy and a control group of 50 healthy control were included. The urinary excretion of EGF, MCP-1, NGAL, KIM-1, L-FABP, β2-microglobulin and DKK-3 was measured in urine samples collected at the day of the renal biopsy. Estimated glomerular filtration rate was measured by the CKD-EPI formula. Interstitial fibrosis area was quantified using a quantitative morphometric procedure and graded according to Oxford Classification. Predictive multivariate models were developed to predict the interstitial fibrosis surface.

Results: Patients with primary IgA Nephropathy showed significantly higher urinary levels of DKK-3, L-FABP and β2-microglobulin, and lower EGF levels than healthy controls. Interstitial fibrosis was negatively correlated with urinary EGF levels and positively with age, proteinuria, eGFR and urinary DKK-3, L-FABP and β2-microglobulin. The best model to predict interstitial fibrosis area accounted for > 60% of its variability and included age, eGFR, proteinuria, DKK-3, EGF, L-FABP and β2-microglobulin.

Conclusions: Our study provides a model to estimate the IFS in IgA Nephropathy which could be useful to monitor the progression of chronic kidney injury.

Keywords: DKK-3; EGF; IgA nephropathy; L-FABP; Renal fibrosis; Urinary biomarkers; β2m.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Biomarkers / urine
  • Case-Control Studies
  • Epidermal Growth Factor / urine
  • Fatty Acid-Binding Proteins / urine
  • Female
  • Fibrosis / urine
  • Glomerular Filtration Rate
  • Glomerulonephritis, IGA* / pathology
  • Glomerulonephritis, IGA* / urine
  • Hepatitis A Virus Cellular Receptor 1
  • Humans
  • Intercellular Signaling Peptides and Proteins / urine
  • Kidney Tubules* / pathology
  • Male
  • Middle Aged
  • beta 2-Microglobulin / urine

Substances

  • Biomarkers
  • Fatty Acid-Binding Proteins
  • beta 2-Microglobulin
  • Epidermal Growth Factor
  • Intercellular Signaling Peptides and Proteins
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • DKK3 protein, human
  • FABP1 protein, human
  • Adaptor Proteins, Signal Transducing