ROLE OF BACTERIAL UREASE IN EXPERIMENTAL PYELONEPHRITIS

Abstract

Evidence has been obtained that Proteus urease is nephrotoxic and that it may contribute to the pathogenesis of pyelonephritis in two ways: (a) By favoring intracellular infection of the tubular epithelium and (b) by creating an alkalinity (pH 8.2) in the kidney that leads to necrosis of renal tubular epithelium and to precipitation of MgNH4PO4 with formation of stones. Intracellular infection was studied in tissue cultures of kidney epithelium containing streptomycin to suppress extracellular infection. Intracellular infection with Proteus mirabilis increased as urea concentration rose and was greatest at 0.2 per cent, the average concentration in whole kidney homogenates. In the absence of streptomycin, both intra and extracellular growth occurred and severe injury to kidney epithelium appeared with 0.1, 0.2, and 0.3 per cent urea as the pH rose above 8.2; but no alkalinity and no injury occurred with lower concentrations of urea. In contrast to Proteus, inoculation of Escherichia coli produced almost no intracellular infection in kidney cells either in vivo or in tissue culture regardless of urea concentration; no rise in pH in either tissue culture, intact kidney tissue, or urine; and no kidney cell injury in tissue culture regardless of urea concentration. Further evidence of Proteus urease nephrotoxicity was obtained by intravascular injection of acetone-killed P mirabilis, the urease activity of which was preserved. These urease-active dead Proteus cells produced sterile pyelonephritis. On the basis of these observations, it is suggested that urease is one of the important agents responsible for the pathogenicity of Proteus in the kidney.