SHIGA TOXIN INDUCES MEDULLARY TUBULAR INJURY IN ISOLATED-PERFUSED RATKIDNEYS

To investigate the potential direct nephrotoxicity of Shiga toxin, a p utative mediator for hemolytic uremic syndrome, purified toxin (10(-11 ) M) was added to isolated rat kidneys perfused for 160 min with a Kre bs-Henseleit acellular medium enriched with albumin and amino acids. K idney function and morphology were examined after perfusion with the S higa toxin vs controls. Shiga toxin did not significantly alter renal perfusion flow, glomerular filtration rate, or tubular sodium reabsorp tion, but it significantly increased urinary protein excretion (from 6 1 +/- 23 to 169 +/- 28 mu g/min, P < 0.01). On renal morphologic study , Shiga toxin did not induce gross glomerular damage but increased mar kedly the injury to the medullary thick ascending limbs. In conclusion , Shiga toxin is toxic to rat kidneys ex vivo and in the absence of pl atelets. Renal damage is manifested by proteinuria and medullary tubul ar injury. The distribution of this injury suggests a possible synergi sm between local medullary hypoxia and the toxic tubular or endothelia l effects of the toxin. These effects may play a pathogenic role in th e tubulo-interstitial injury observed in hemolytic uremic syndrome ass ociated with severe renal failure.