title: Glomerular injury and tubular loss in adriamycin nephrosis.
abstract: Glomerular injury manifested by sustained proteinuria usually leads to tubule injury and reduction of the GFR. The current study explored the link between these processes in rats with adriamycin nephrosis. One group of nephrotic rats received a vasopressin V2 receptor blocker (V2X) from 4 to 16 wk after injection of adriamycin, whereas a second group received no treatment (NoRx). V2 receptor blockade increased urine volume without affecting protein excretion. At 16 wk, both groups of nephrotic rats exhibited a marked reduction in GFR in comparison with normal controls (V2X, 0.22 +/- 0.19 ml/min; NoRx, 0.20 +/- 0.11 ml/min; control, 1.23 +/- 0.11 ml/min). Morphologic studies revealed that the majority of glomeruli in nephrotic rats were no longer connected to normal tubule segments (V2X, 81 +/- 21%; NoRx, 85 +/- 18%; control, 1 +/- 2%). Glomeruli without tubules were not, however, globally sclerosed. Disruption of the glomerular tubular junction was associated with the presence of amorphous material separating damaged tubule cells from the basement membrane. Serial sections revealed that this material spread from extensive areas of adhesion between the glomerular tuft and capsule to invest the tubular neck. Reduction of the GFR was strongly correlated with the fraction of glomeruli not connected to normal tubules (r(2) = 0.82; P < 0.0001). V2 receptor blockade did not preserve renal function or structure. These findings suggest that local extension of glomerular injury to destroy the tubule neck is an important cause of loss of renal function in adriamycin nephrosis.
authors: Departments of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto; and Department of Pathology, University of California, San Francisco, California.
authors: Basit
authors: B
authors: Javaid
authors: Departments of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto; and Department of Pathology, University of California, San Francisco, California.
authors: Jean L
authors: JL
authors: Olson
authors: Departments of Medicine, VA Palo Alto Health Care System and Stanford University, Palo Alto; and Department of Pathology, University of California, San Francisco, California.
authors: Timothy W
authors: TW
authors: Meyer
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D004231:Diuresis / Q000187:drug effects; D004317:Doxorubicin; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology; D007678:Kidney Glomerulus / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D011507:Proteinuria / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000494:pharmacology*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D009025:Morpholines; D013141:Spiro Compounds; D004317:Doxorubicin; C103281:satavaptan