Immunohistochemical Markers of Renal Tubular Injury and Cyclosporin Nephrotoxicity in Kidney Allograft Biopsies

Dr. Raimundo García Del Moral, Departamento de Anatomía Patológica, Facultad de, Medicina, Universidad de Granada, Avda. de Madrid, s/n, E-18012 Granada (Spain) Dear Sir, The differential diagnosis between renal allograft rejection and chronic cyclosporin (CS) nephrotoxicity presents serious difficulties for the histopathologist [1]. Vimentin expression in the cytoplasm of proximal tubule cells from drug-induced toxic nephropathies suggests that this intermediate filament could be used as a marker of both active cell regeneration and irreversible chronic tubular injury [2]. Chronic tubular injury has also been associated to changes in the expression of other antigens such as the epithelial membrane antigen (EMA), which is normally expressed by the distal tubule and collecting duct [3], and the CD15 antigen (Leu Ml) on the proximal tubule brush border [4]. We have studied the expression of vimentin, EMA and CD15 in 48 renal allograft biopsies from patients subject to 2 different immunosuppressive protocols: prednisone plus low-dose CS (n = 31), and prednisone plus azathioprine (AZA; n = 17). Controls (n = 10) were obtained from otherwise normal kidneys removed after traumatic rupture. In the group treated with CS, a histopathological diagnosis of glomerulointerstitial allograft rejection was reached in 18 cases, while 5 of them showed chronic vasculointerstitial rejection, 4 acute interstitial rejection, 2 acute vascular rejection, 1 chronic transplant glom-erulopathy and 1 recidivant focal and seg-mental hyalinosis. Among those patients treated with AZA, the most common histolog-ical diagnosis was chronic vasculointerstitial rejection (5 cases), followed by acute vascular rejection (4 cases), acute interstitial rejection (4 cases) and acute glomerulointerstitial rejection (4 cases). All biopsies were evaluated in a semiquantitative manner (0 = absent; l = mild; 2 = severe) for the presence of CSassociated changes including striped interstitial fibrosis, tubular calcifications, megamitochondria and hyaline droplets in the proximal tubules, peritubular capillary congestion, vascular myointimal fibrosis and hyaline arteri-opathy. Ultrastructural confirmation of megamitochondria and hyaline droplets was performed in 50% of cases. The expression of vimentin, EMA and CD15 by the tubular cells was analyzed by avidin-biotin immunoperoxidase in paraffin-embedded tissue sections. The number of immunostained tubular profiles per 10 high-power (400 ×) microscopic fields was assessed.