title: Acute inflammation is the harbinger of glomerulosclerosis in anti-glomerular basement membrane nephritis.
abstract: The degree of glomerular inflammation and injury during immune-mediated glomerulonephritis is felt to be critical to the eventual development of glomerulosclerosis, although the relative contributions of acute and chronic inflammation are uncertain. By grading the initial dose of antibody in accelerated anti-glomerular basement membrane nephritis, we observed that only animals with the most substantial acute inflammation (in terms of neutrophil influx and acute proteinuria) developed sustained proteinuria followed by an increase in serum creatinine and evidence of severe glomerulosclerosis. Chronic inflammation (i.e., glomerular macrophage influx and evidence of glomerular cell proliferation), in contrast, was evident without the development of glomerulosclerosis. Decreasing the degree of acute inflammation during severe nephritis by complement depletion diminished both the initial and sustained proteinuria and the influx of neutrophils, prevented the terminal increase in serum creatinine, and attenuated the evolution of glomerulosclerosis. Complement depletion, however, did not affect peak proteinuria, macrophage influx, or glomerular cell proliferation. Regression analysis of the entire data set demonstrated that acute (day 1) proteinuria was predictive of the eventual histopathological index, more so than chronic (day 7) proteinuria. To recapitulate, glomerulosclerosis following antiglomerular basement membrane nephritis appears to be substantially dependent on the degree of acute inflammatory injury.
authors.affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
authors.forename: A L
authors.initials: AL
authors.lastname: Scandrett
authors.forename: J
authors.initials: J
authors.lastname: Kissane
authors.forename: J B
authors.initials: JB
authors.lastname: Lefkowith
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001485:Basement Membrane / Q000276:immunology; D003165:Complement System Proteins / Q000172:deficiency; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000276:immunology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D009393:Nephritis / Q000276:immunology*; D011507:Proteinuria / Q000150:complications; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors
chemical_list: D000906:Antibodies; D003165:Complement System Proteins