Vimentin expression and distal tubular damage in the rat kidney.
Renal damage and repair was investigated in Wistar rats after administering 40 or 80 mmol lithium chloride/kg dry food during 3 or 7 weeks. Serum creatinine levels remained normal. Light microscopic signs of injury were confined to the cortical and outer medullary collecting ducts (CDs) and to the distal convoluted tubules (DCTs; 39-97% of the cross-sections contained necrotic cells); no lesions were found in proximal tubules and thick ascending limbs (TALs). Nevertheless, the urinary excretion of N-acetyl-beta-D-glucosaminidase was increased in the high-dose group, but epidermal growth factor immunostaining in the TALs and DCTs was unchanged. Simultaneously, increased cell proliferation in the CDs and also the DCTs was accompanied by the appearance of vimentin immunostaining predominantly in the basal cell pole; the number of vimentin-positive cells amounted to 72% in the CDs of the high dose group after 3 weeks. In addition, in all lithium-treated animals, the interstitium throughout the entire kidney, but mainly around injured distal segments, displayed increased cell proliferation and leukocyte infiltration (antibody OX-1 positive); 7-25% of these were macrophages (antibody ED-1 positive). Collagen I and III and laminin staining patterns were not altered.


CONCLUSIONS
(1) LiCl-induced damage and regeneration confined to the DCTs and CDs is accompanied by the expression of vimentin, possibly in response to an increased requirement for cell spreading and motility after epithelial desquamation, and (2) interstitial cell proliferation and leukocyte infiltration, largely confined around the injured nephron segments, may constitute early signs of the development of lithium-induced interstitial nephropathy.
Zhu
M Q
MQ
Department of Nephrology-Hypertension, University of Antwerp, Belgium.
De Broe
M E
ME
Nouwen
E J
EJ
D000118:Acetylglucosaminidase / Q000652:urine; D000818:Animals; D002455:Cell Division; D004815:Epidermal Growth Factor / Q000032:analysis; D004848:Epithelium / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D007684:Kidney Tubules / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D007685:Kidney Tubules, Collecting / Q000473:pathology; D007962:Leukocytes / Q000473:pathology; D018021:Lithium Chloride / Q000008:administration & dosage; D008264:Macrophages / Q000473:pathology; D008297:Male; D009318:Natriuresis; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000378:metabolism*
D014746:Vimentin; D004815:Epidermal Growth Factor; D000118:Acetylglucosaminidase; D018021:Lithium Chloride