Evolution of experimentally induced papillary necrosis to focal segmental glomerulosclerosis and nephrotic proteinuria.
Bromoethylamine (BEA)-induced papillary necrosis is a reproducible model for analgesic nephropathy. We induced this lesion in groups of male Sprague-Dawley rats and followed the functional and histological changes for 1 year. We found that by 1 month, necrosis of the papilla was complete, glomerular filtration rate was depressed, and urine albumin excretion was increased. There was an extensive interstitial fibrosis characterized by a mononuclear cell infiltrate and patchy tubular atrophy. By 6 months, there was re-epithelialization of the papillary stump accompanied by a marked increase in albuminuria and an improvement in concentrating ability. Changes seen at 9 months were more advanced. There was extensive cortical fibrosis manifested by pitting of the surface of the kidney. At 1 year, renal function remained impaired (creatinine clearance reduced by 65% to 0.26 mL/min/100 g), and the animals were now markedly nephrotic, with albuminuria of 254 mg of albumin/24 h. In the BEA rats, there was selective destruction of the deep nephrons leading to an increase in the volume-ratio of superficial to deep nephrons. Glomerular changes, affecting approximately 60% of the glomeruli, were characteristic of focal segmental glomerular sclerosis. This model of papillary necrosis/interstitial fibrosis is associated with chronic renal insufficiency and leads to the development of focal glomerular sclerosis and nephrotic proteinuria by 6 to 12 months after its induction.
Garber
S L
SL
Divisions of Nephrology at Cook County Hospital, University of Illinois College of Medicine, Chicago, IL, USA. slgarber@aol.com
Mirochnik
Y
Y
Arruda
J A
JA
Dunea
G
G
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D005021:Ethylamines; D005355:Fibrosis; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000473:pathology*; D007679:Kidney Medulla / Q000473:pathology; D007681:Kidney Papillary Necrosis / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D011507:Proteinuria / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005021:Ethylamines; C004504:2-bromoethylamine; D003404:Creatinine