Angiotensin-converting enzyme in non-neoplastic kidney diseases

The angiotensin I-converting enzyme (ACE, CD143, kininase II) plays a critical role in controlling the level of vasoactive peptides such as angiotensins and kinins in the local circulations and tissue interstitium. Because recent work has documented a vessel-, organ-, and species-specific pattern of endothelial ACE expression in the vascular system, we have analyzed whether or not changes of this pattern occur in vessels, tubules, and interstitium of the human kidney that is affected by different non-neoplastic diseases.

Using a set of well-characterized monoclonal antibodies (mAbs), ACE was assessed on renal tissue of 135 patients by immunohistochemistry, including an additional analysis at the ultrastructural level. A semiquantitative evaluation allowed the estimation and comparison of ACE content in different renal compartments. These data were compared with several clinical findings, diagnosis, therapeutic modalities, and histological features.

In contrast to the normal human kidney, where ACE is abundant in the brush border of the proximal tubule but is usually absent in endothelial cells of any vessel type, an endothelial neoexpression of ACE was observed in different diseases. In general, this neoexpression was associated with histological sites of interstitial fibrosis and showed some selectivity for glomerular endothelial cells in diabetes mellitus and chronic arterial hypertension. There was also a loss of epithelial ACE in the proximal tubule in certain pathological conditions, for example, in chronic fibroplastic processes, acute pyelonephritis, and different stages of acute renal failure.

Neoexpression of ACE by renal endothelial cells, as well as changes of the tubular ACE content, is a common finding in diseased human kidneys. As associated with certain tissue sites, clinical and/or morphological features, these changes may be involved in parenchymal remodeling and renal pathophysiology.