title: Nephrotic urine prevents increased rat glomerular albumin permeability induced by serum from the same patient with idiopathic nephrotic syndrome.
abstract: BACKGROUND
  The putative humoral mediator thought to be involved in the pathogenesis of idiopathic nephrotic syndrome has not yet been identified. However, components exist in normal serum that block the permeability activity of FSGS serum in vitro. The potential of FSGS serum to increase glomerular albumin permeability may result from an imbalance between permeability factors and naturally occurring inhibitors. We hypothesized that this imbalance may be favoured by loss of inhibitory factors in nephrotic urine.
  
  
  METHODS
  The study population consisted of seven patients with biopsy-proven FSGS, one with IgM nephropathy, and three with idiopathic nephrotic syndrome without biopsy, from whom frozen serum and dialysed and lyophilized urine samples were available. Glomerular albumin permeability (P(alb)) was determined from the change in glomerular volume induced by applying oncotic gradients across the basement membrane of normal isolated rat glomeruli pre-incubated with patient serum, normal control serum, patient serum mixed with an equal volume of urine from the same patient, or patient serum mixed with normal urine. Serum and urine apolipoproteins J and E were measured by dot-blot, utilizing peroxidase-labelled antibodies. The urinary capacity to scavenge oxygen radicals was determined after exposure of isolated glomeruli to superoxide generated by xanthine and xanthine oxidase.
  
  
  RESULTS
  The mean P(alb) of the patients was markedly elevated at 0.74+/-0.08. The addition of urine from the same patient significantly reduced P(alb) (mean 0.15+/-0.23) in all but one of the patients with FSGS. Normal urine had no inhibitory effect in the 10 patients in which it was tested (mean 0.71+/-0.09). Serum apo J was slightly decreased and serum apo E was slightly increased compared with controls. Urine levels of both lipoproteins were significantly decreased compared with controls. Urine from FSGS patients effectively neutralized superoxide, whereas normal urine did not.
  
  
  CONCLUSIONS
  Nephrotic urine but not normal urine contains components that block increased albumin permeability in isolated rat glomeruli induced by serum from patients with the idiopathic nephrotic syndrome. The inhibitory function of these components, which appear not to include apolipoproteins J and E, may involve scavenging of superoxide as a final common pathway. Loss in the urine from the serum of naturally occurring inhibitors in the initial stages of the disease may propagate proteinuria and glomerular injury.
authors.affiliation: Department of Medicina Clinica, University of Trieste, Trieste, Italy. m.carraro@fmc.units.it
authors.forename: Michele
authors.initials: M
authors.lastname: Carraro
authors.forename: Cristina
authors.initials: C
authors.lastname: Zennaro
authors.forename: Giovanni
authors.initials: G
authors.lastname: Candiano
authors.forename: Luca
authors.initials: L
authors.lastname: Musante
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bruschi
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Mary
authors.initials: M
authors.lastname: Artero
authors.forename: Luigi
authors.initials: L
authors.lastname: Faccini
mesh_terms: D000293:Adolescent; D000328:Adult; D000418:Albumins / Q000378:metabolism*; D000419:Albuminuria / Q000503:physiopathology*; D000818:Animals; D001053:Apolipoproteins / Q000037:antagonists & inhibitors / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood / Q000378:metabolism; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008297:Male; D009404:Nephrotic Syndrome / Q000097:blood* / Q000378:metabolism; D010539:Permeability; D011336:Probability; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D014556:Urine
chemical_list: D000418:Albumins; D001053:Apolipoproteins