HUMAN ACUTE TUBULAR-NECROSIS - A LECTIN AND IMMUNOHISTOCHEMICAL STUDY

To determine the nephron segment distribution of tubular epithelial da mage and regeneration and the proliferative activity of various nephro n segments in human acute tubular necrosis (ATN) with an antibody to p roliferating cell nuclear antigen (PCNA) and to compare the findings i n native kidneys with ATN with those in transplant kidneys with ATN, a rchival tissues from 12 native and 21 transplant kidney biopsy specime ns and nine transplant nephrectomy specimens were collected that all s howed obvious morphological signs of ATN. Nineteen patients with trans plant kidneys with ATN were immunosuppressed with cyclosporine and 11 were immunosuppressed with prednisone and azathioprine. There was a pr edominance of ''regenerating'' tubules (tubules with thin epithelium) in the distal nephron in native kidneys with ATN; in the transplant ki dneys this was less conspicuous. The number of Tamm-Horsfall protein ( THP)-positive tubules was decreased in all kidneys with ATN compared w ith normal human kidneys. In contrast, the number of THP-positive cast s was much higher in all kidneys with ATN than in the normal kidneys. In transplant kidneys with ATN the number of THP-positive casts was su bstantially lower than in native kidneys with ATN. The macula densa ap pears to maintain its morphological integrity in kidneys with ATN. Bot h regenerating and normal appearing tubules expressed vimentin and HLA -DR. The proliferation index (PI; ie, percentage of PCNA-positive nucl ei) of the renal tubular epithelium in normal control kidneys varied b etween 0.22 and 0.33, depending on the tubule segment. The highest PI was noted in the transplant kidneys with ATN not treated with cyclospo rine (8.0), followed by the native kidneys with ATN (4.4) and the tran splant kidneys with ATN treated with cyclosporine (4.3). We did not fi nd any significant difference in the PI between the regenerating (5.0) and normal appearing (5.6) tubules. Proximal tubules (8.7) showed sig nificantly higher PI values than distal tubules (3.5) in transplant ki dneys with ATN. Our results show substantial differences between nativ e kidneys and transplant kidneys with ATN. Tubular epithelial cell pro liferation in human ATN is prominent and appears to correlate with the severity of ATN. Light microscopically normal appearing tubules and r egenerating: tubules participate equally in the regeneration of injure d tubules. Cyclosporine may have an inhibitory effect on cell regenera tion (proliferation) in human transplant kidneys with ATN. Copyright ( C) 1995 by W.B. Saunders Company