VASCULAR AND GLOMERULAR EFFECTS OF CLOSTRIDIUM-DIFFICILE TOXIN-A PEPTIDE ON THE ISOLATED RAT-KIDNEY

Toxin A peptide from Clostridium difficile caused damage and secretion in the intestinal mucosa. These effects are mediated in part by pro-i nflammatory substances. In order to evaluate and compare the biologic effect of toxin A on renal vascular, glomerular and tubular functions, we studied this toxin in isolated rat kidneys. Isolated kidneys from adult male Wistar rats (260-320 g) were perfused with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin. We studied the effect of toxin A peptide (3.2 x 10(-6) M, injected into perfusat e) on glomerular filtration rate (GFR), urinary flow rate (UF) and tot al sodium reabsorption (TNa+, %). All experiments were preceded by a 3 0-min basal period, and in another group of kidneys the time course of the variables was followed without toxin infusion for unpaired contro l. Toxin A (TxA) reduced the perfusion pressure (PP), from PPcontrol/3 0min = 124.89 +/- 1.91 to PPTxA/120min = 88.13 +/- mmHg (N = 6, P<0.01 ) with a maximal effect at 120 min after toxin infusion. TxA also caus ed a significant decrease in GFR with maximal effect at 90 min after t oxin infusion (GFR(control/30min) = 0.53 +/- 0.05 to GFR(TxA/90min) = 0.30 + 0.05 ml min(-1)g(-1);N = 6,P<0.01). TxA did not alter renal tub ular sodium transport when compared with a control without toxin infus ion. In addition, toxin-treated kidneys caused a time-dependent increa se in urinary flow from UFcontrol/30min = 0.16 +/- 0.08 to UFTxA/120mi n = 0.35 +/- 0.1 ml min(-1) g(-1) (N = 6, P<0.05). These data demonstr ate renal vascular, glomerular and urinary effects of C. difficile tox in A.