THE ROLE OF MEPRIN-A IN THE PATHOGENESIS OF ACUTE-RENAL-FAILURE

Meprin A is a zinc-dependent metallo-endopeptidase that is present in the brush border membrane of renal proximal tubular epithelial cells. Although this enzyme has been detected in the kidney of mammalian spec ies and its biochemical structure and action have been characterized, the role of this endopeptidase in normal renal physiology and in disea se states is unknown. Therefore, we assessed the susceptibility of inb red strains of mice with normal and low meprin A activity to ischemic and nephrotoxic acute renal failure. We report that two normal meprin A strains of mice, C57BL/6 and DBA/2, developed more severe renal func tional and structural injury following either bilateral renal artery c lamping or the injection of hypertonic glycerol, compared to two low m eprin A strains, C3H/He and CBA. These findings suggest that meprin A plays a role in the pathophysiology of acute renal failure following a variety of insults insults to the kidney. We propose that redistribut ion of this metalloendopeptidase to the basolateral membrane domain du ring acute renal failure results in degradation of the extracellular m atrix and damage to adjacent peritubular structures. (C) 1995 Academic Press, Inc.