Nephrol Dial Transplant (2003) 18: 689-693
© 2003 European Renal Association-European Dialysis and Transplant Association
Nephrotic urine prevents increased rat glomerular albumin permeability induced by serum from the same patient with idiopathic nephrotic syndrome
1 Department of Medicina Clinica, University of Trieste, Trieste, 2 Division of Nephrology, Istituto G. Gaslini, Genoa and 3 Department BBCM, University of Trieste, Trieste, Italy
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 (Palb) 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 Palb of the patients was markedly elevated at 0.74±0.08. The addition of urine from the same patient significantly reduced Palb (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.
Keywords: apolipoproteins; FSGS; glomeruli; nephrotic syndrome; permeability factors; urine
Correspondence and offprint requests to: Michele Carraro MD, Dipartimento di Medicina Clinica, Università degli Studi di Trieste, Ospedale di Cattinara, Strada di Fiume, 447, 34149 Trieste, Italy. Email: m.carraro{at}fmc.units.it
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