4.1.3 Tubulonecrotic ATN and variants

Definition: Overt or minor tubular necrosis without or with but signs of regeneration,focal or diffuse tubular atrophy and interstitial fibrosis

Tubulonecrotic ATN with overt necrosis

For this type of ATN the term is correct. The hallmark is necrosis mainly of the proximal tubules, but other parts of the nephron may also be affected. In most severe forms all tubules are involved to the same degree, in other cases tubules with complete necrosis may be found side by side with better preserved ones. The necrotic epithelium becomes detached from the underlying BM and the tubules are filled with cell debris. At this stage of evolution the tubules become surrounded by neutrophils and the cell debris in the tubular lumens may also contain neutrophils. A destruction of the BM is not part of the picture. The BM may not be stainable with PAS or silver but by EM destruction is not seen.  The interstitial space is widened by edema. In later stages regeneration of the epithelium takes place so that virtually all tubular epithelial cells show positivity for mib 1. Repair of the tubular epithelium results in the beginning to an irregular lining of the BM by de-differentiated epithelial cells. The cytoplasm may be as thin as the endothelium. The nuclei are often enlarged and multinucleated epithelial cells may be found. Interstitial fibrosis and scattered lymphocytes and histiocytes are present as well.  With time complete regeneration of the tubular epithelium may ensue. Personally I have never had the opportunity to evaluate rebiopsies after extensive overt tubular necrosis.

Tubulonecrotic ATN: variants

The diagnosis of “acute tubular necrosis“ in cases with minor tubular epithelial cell necrosis is often difficult.  There are only (if any) a few necrotic tubular epithelial cells, often  detached in the tubular lumen,  or  isolated mitoses and occasionally only prominent tubular cell nuclear polymorphism.  In such cases immunohistochemical staining for Mip-1 (Ki67) can reveal the true extent of regeneration. Frequently, these changes in the tubular epithelium are accompanied by variable tubular dilatation, interstitial edema and/or fibrosis and incipient focal tubular atrophy. The interstitium usually reveals a scattered, mainly lymphohistiocytic infiltration. Isolated polymorphonuclear leukocytes are sometimes found in the tubules. In advanced stages, the interpretation of such cases as late stages of primarily „acute tubular necrosis“ may be impossible. Immunohistochemistry for Mip-1 is always recommended in doubtful cases. There is great danger that advanced cases will be incorrectly classified as „chronic interstitial nephritis“ or “chronic unspecific tubulo-interstitial damage“.