Truong L D, Farhood A, Tasby J, Gillum D
Department of Pathology, Methodist Hospital, Houston, Texas.
Kidney Int. 1992 Jun;41(6):1676-89. doi: 10.1038/ki.1992.241.
Although unilateral clamping of the renal artery to induce chronic ischemia of the kidney tissue has been utilized in several animal species, the resultant morphologic, ultrastructural and immunologic changes have never been well characterized. Moreover, the pathogenesis of these changes, as well as their roles in causing or facilitating the development of chronic tubulointerstitial nephritis have not been known. To examine some of these issues, male Sprague-Dawley rats were subjected to unilateral stenosis of the left main renal artery for 28 days. Stenotic and contralateral kidneys of experimental animals and kidneys from sham-operated controls were subjected to: (1) light microscopic, electron microscopic and immunofluorescent studies; (2) morphometric quantitation of the structural changes; (3) staining for actin, epithelial membrane antigen, keratin, and vimentin by immunoperoxidase technique; (4) staining for complex glycoproteins by a panel of 13 lectins; and (5) phenotyping and quantitation of the interstitial inflammatory infiltrates by monoclonal antibodies, using immunoperoxidase technique. The results reveal that: (1) The ischemic kidney tissue displays marked tubulointerstitial damages including abundant interstitial chronic inflammatory infiltrates, with good preservation of glomerular structure, which is consistent with the standard criteria of chronic tubulointerstitial nephritis. (2) The antigenic profile of the ischemic tubular epithelium displayed marked alterations including a neo-expression of vimentin and keratin, as well as a loss of endogenous avidin binding activity, Ia antigen and several complex surface glycoproteins detectable by lectins. (3) Neither electron dense deposits nor immunoglobulins are detectable in the kidneys from experimental or control animals. (4) Tubulitis, defined as infiltration of tubular epithelium by inflammatory cells, was present in up to 42.2% of tubular cross sections of the ischemic kidneys. (5) The interstitial inflammatory infiltrates were composed of B lymphocytes, T helper lymphocytes, and macrophages whereas the T non-helper lymphocytes were scanty, a phenotypic pattern similar to that of several other experimental rat models of chronic tubulointerstitial nephritis. It is concluded that: (1) In the Sprague-Dawley rats, ischemia alone can cause a constellation of changes fulfilling the accepted features of chronic interstitial nephritis; (2) ischemia alters the antigenic profile of the tubular epithelium and thereby may initiate a cell mediated immune response, accounting for the observed tubulitis and interstitial inflammation; and (3) ischemia may well be the final common pathway for chronic tubulointerstitial nephritis of diverse etiologies.
