title: Distinct urinary lipid profile in children with focal segmental glomerulosclerosis.
abstract: BACKGROUND
  Focal segmental glomerulosclerosis (FSGS) accounts for the majority of new-onset end-stage renal disease (ESRD) during adolescence. FSGS treatment is a great challenge for pediatric nephrologists due to intertwined molecular pathways underlining its complex pathophysiology. There is emerging evidence showing that perturbed lipid metabolism plays a role in the pathophysiology of FSGS.
  
  
  METHODS
  We postulate that the nephrotic milieu in FSGS differs from minimal change disease (MCD) and that urinary lipidomics can be used as a tool for early diagnosis of FSGS. We explored the urinary lipid profile of patients with FSGS and MCD using an unbiased metabolomics approach.
  
  
  RESULTS
  We discovered a unique lipid signature characterized by increased concentration of fatty acid (FA) and lysophosphatidylcholines (LPC) and a decrease in urinary concentration of phosphatidylcholine (PC) in patients with FSGS. These findings indicate increased metabolism of membrane phospholipid PC by phospholipase A2 (PLA2), resulting in higher urinary concentrations of LPC and FA.
  
  
  CONCLUSIONS
  We propose that increased PC by-products can be used as a biomarker to diagnose FSGS and shed light on the mechanism of tubular and podocyte damage. Validation of identified urinary lipids as a biomarker in predicting the diagnosis and progression of FSGS in a larger patient population is warranted.
authors.affiliation: Division of Pediatric Nephrology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7022, Cincinnati, OH, 45229, USA. Elif.Erkan@cchmc.org.
authors.forename: Elif
authors.initials: E
authors.lastname: Erkan
authors.affiliation: Department of Pathology, Children's Hospital of Cincinnati, Cincinnati, OH, USA.
authors.forename: Xueheng
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Children's Hospital of Cincinnati, Cincinnati, OH, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Setchell
authors.affiliation: Division of Pediatric Nephrology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue MLC 7022, Cincinnati, OH, 45229, USA.
authors.forename: Prasad
authors.initials: P
authors.lastname: Devarajan
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D042241:Early Diagnosis; D005227:Fatty Acids / Q000652:urine; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000652:urine*; D006801:Humans; D008055:Lipids / Q000652:urine*; D008244:Lysophosphatidylcholines / Q000652:urine; D008297:Male; D055432:Metabolomics / Q000379:methods; D010713:Phosphatidylcholines / Q000652:urine; D011237:Predictive Value of Tests; D011379:Prognosis; D053719:Tandem Mass Spectrometry; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D008055:Lipids; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines
keywords: Biomarker; Children; Focal segmental glomerulosclerosis; Metabolomics; Minimal change disease; Phospholipase A2; Urinary lipidomics