NMR and MS urinary metabolic phenotyping in kidney diseases is fit-for-purpose in the presence of a protease inhibitor

Mol Omics. 2019 Feb 11;15(1):39-49. doi: 10.1039/c8mo00190a.


Nephrotic syndrome with idiopathic membranous nephropathy as a major contributor, is characterized by proteinuria, hypoalbuminemia and oedema. Diagnosis is based on renal biopsy and the condition is treated using immunosuppressive drugs; however nephrotic syndrome treatment efficacy varies among patients. Multi-omic urine analyses can discover new markers of nephrotic syndrome that can be used to develop personalized treatments. For proteomics, a protease inhibitor (PI) is sometimes added at sample collection to conserve proteins but its impact on urine metabolic phenotyping needs to be evaluated. Urine from controls (n = 4) and idiopathic membranous nephropathy (iMN) patients (n = 6) were collected with and without PI addition and analysed using 1H NMR spectroscopy and UPLC-MS. PI-related data features were observed in the 1H NMR spectra but their removal followed by a median fold change normalisation, eliminated the PI contribution. PI-related metabolites in UPLC-MS data had limited effect on metabolic patterns specific to iMN. When using an appropriate data processing pipeline, PI-containing urine samples are appropriate for 1H NMR and MS metabolic profiling of patients with nephrotic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Decision Making
  • Discriminant Analysis
  • Female
  • Glomerulonephritis, Membranous / metabolism
  • Glomerulonephritis, Membranous / urine
  • Humans
  • Kidney Diseases / metabolism*
  • Kidney Diseases / urine*
  • Least-Squares Analysis
  • Magnetic Resonance Spectroscopy*
  • Male
  • Metabolomics*
  • Middle Aged
  • Phenotype
  • Principal Component Analysis
  • Protease Inhibitors / pharmacology*
  • Tandem Mass Spectrometry


  • Biomarkers
  • Protease Inhibitors