VIMENTIN EXPRESSION AND DISTAL TUBULAR DAMAGE IN THE RAT-KIDNEY

Renal damage and repair was investigated in Wistar rats after administ ering 40 or 80 mmol lithium chloride/kg dry food during 3 or 7 weeks. Serum creatinine levels remained normal. Light microscopic signs of in jury were confined to the cortical and outer medullary collecting duct s (CDs) and to the distal convoluted tubules (DCTs; 39-97% of the cros s-sections contained necrotic cells); no lesions were found in proxima l 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 an d DCTs was unchanged. Simultaneously, increased cell proliferation in the CDs and also the DCTs was accompanied by the appearance of vimenti n immunostaining predominantly in the basal cell pole; the number of v imentin-positive cells amounted to 72% in the CDs of the high dose gro up after 3 weeks. In addition, in all lithium-treated animals, the int erstitium throughout the entire kidney, but mainly around injured dist al segments, displayed increased cell proliferation and leukocyte infi ltration (antibody OX-1 positive); 7-25% of these were macrophages (an tibody ED-1 positive). Collagen I and III and laminin staining pattern s were not altered. In conclusion: (1) LiCl-induced damage and regener ation confined to the DCTs and CDs is accompanied by the expression of vimentin, possibly in response to an increased requirement for cell s preading and motility after epithelial desquamation, and (2) interstit ial cell proliferation and leukocyte infiltration, largely confined ar ound the injured nephron segments, may constitute early signs of the d evelopment of lithium-induced interstitial nephropathy.