Interstitial alterations in renal cortex in acute tubular necrosis (ATN) post-renal transplantation and in patients with ATN not related to renal transplant.

:  Background:  Abnormalities of renal function with long-term implications can persist after acute tubular necrosis (ATN), probably because of permanent loss of nephrons. Residual areas of fibrosis are also observed in the renal cortex post-ATN. In this study, we investigate the interstitial alterations post-ATN using histological and immunohistochemical methods. Methods:  We studied 11 patients with ATN of different etiologies and 19 patients with ATN post-renal transplantation. Eleven patients with ATN post-renal transplantation and one with ATN not related to renal transplantation were submitted to more than one biopsy because of delayed renal function recovery. The immunohistochemical studies were performed using α-smooth muscle-actin (α-SM-actin), endothelin, nuclear factor-κB (NF-κB), Jun-N-terminal kinase (p-JNK) and fibronectin antibodies. We also analyzed the urinary content of transforming growth factor-β (TGF-β) during the acute phase of ATN. Results:  The immunohistochemical studies showed increased α-SM-actin, fibronectin, endothelin, p-JNK and NF-κB staining in the tubulointerstitium area from the renal cortex of all patients when compared with controls (p < 0.001), and these increase persisted in the patients submitted to sequential biopsies. One of the patients with ATN without renal transplant and six patients with ATN post-renal transplant developed chronic renal failure. There was a significant increase of TGF-β excretion in the urine of patients with acute renal failure (p < 0.01) compared with control. Conclusion:  Our data show that the enhancement of renal TGF-β production and the persistent increase of myofibroblasts, fibronectin, endothelin, p-JNK and NF-κB in renal cortex tubulointerstitium post-ATN may explain the impaired recovery of renal function observed in patients post-ATN frequently observed in patients with ATN post-renal transplant.