title: Identification of urinary metabolites that distinguish membranous lupus nephritis from proliferative lupus nephritis and focal segmental glomerulosclerosis.
abstract: BACKGROUND
  Systemic lupus erythematosus (SLE or lupus) is a chronic autoimmune disease, and kidney involvement with SLE, a.k.a. lupus nephritis (LN), is a frequent and severe complication of SLE that increases patient morbidity and mortality. About 50% of patients with SLE encounter renal abnormalities which, if left untreated, can lead to end-stage renal disease. Kidney biopsy is considered the criterion standard for diagnosis and staging of LN using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, which was developed to help predict renal outcomes and assist with medical decision-making. However, kidney biopsy-based classification of LN is highly invasive and impractical for real-time monitoring of LN status. Here, nuclear magnetic resonance (NMR) spectroscopy-based metabolic profiling was used to identify urinary metabolites that discriminated between proliferative and pure membranous LN as defined by the ISN/RPS classification, and between LN and primary focal segmental glomerulosclerosis (FSGS).
  
  
  METHODS
  Metabolic profiling was conducted using urine samples of patients with proliferative LN without membranous features (Class III/IV; n = 7) or pure membranous LN (Class V; n = 7). Patients with primary FSGS and proteinuria (n = 10) served as disease controls. For each patient, demographic information and clinical data was obtained and a random urine sample collected to measure NMR spectra. Data and sample collection for patients with LN occurred around the time of kidney biopsy. Metabolic profiling analysis was done by visual inspection and principal component analysis.
  
  
  RESULTS
  Urinary citrate levels were 8-fold lower in Class V LN compared to Class III/IV patients, who had normal levels of urinary citrate (P < 0.05). Class III/IV LN patients had > 10-fold lower levels of urinary taurine compared to Class V patients, who had mostly normal levels (P < 0.01). Class V LN patients had normal urinary hippurate levels compared to FSGS patients, who completely lacked urinary hippurate (P < 0.001).
  
  
  CONCLUSIONS
  This pilot study indicated differences in urinary metabolites between proliferative LN and pure membranous LN patients, and between LN and FSGS patients. If confirmed in larger studies, these urine metabolites may serve as biomarkers to help discriminate between different classes of LN, and between LN and FSGS.
authors.affiliation: Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056, USA.
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: Romick-Rosendale
authors.forename: Hermine I
authors.initials: HI
authors.lastname: Brunner
authors.forename: Michael R
authors.initials: MR
authors.lastname: Bennett
authors.forename: Rina
authors.initials: R
authors.lastname: Mina
authors.forename: Shannen
authors.initials: S
authors.lastname: Nelson
authors.forename: Michelle
authors.initials: M
authors.lastname: Petri
authors.forename: Adnan
authors.initials: A
authors.lastname: Kiani
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kennedy
mesh_terms: D019343:Citric Acid / Q000652:urine; D003937:Diagnosis, Differential; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine; D015433:Glomerulonephritis, Membranous / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine; D006626:Hippurates / Q000652:urine; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D025341:Principal Component Analysis; D012372:ROC Curve; D013654:Taurine / Q000652:urine
chemical_list: D006626:Hippurates; D013654:Taurine; D019343:Citric Acid; C030514:hippuric acid