The human kidney contains two types of alkaline phosphatase (AP) isoenzymes: a hepatic type of AP and an intestinal-like AP. Intestinal-like AP, measured by immunotitration techniques, is a minor component (1 to 4%) of the total AP activity. It is found only in the particle-free fraction (cytoplasm) and is located, with immunofluorescent techniques, in some of the proximal convoluted tubules. Urinary AP activity is found after high-speed centrifugation in the supernatant (x 100,000g), as well as in the sediment, and may be extracted from the sediment after solubilization with n-butanol. Both types of these renal isoenzymes contribute to urinary AP activity. Biochemical characterization (effect of inhibitors, thermostability, denaturing with urea, and so on) revealed that urinary intestinal-like AP and renal intestinal-like AP are identical. Both, however, have been distinguished as multiple forms of AP from the small intestine. Most of the urinary AP activity of healthy persons (22 volunteers) was found in the sediment and consisted of liver-type AP. Urinary AP of patients with diseases, after application of potentially nephrotoxic drugs or during rejection episodes of renal allografts, contains little sediment activity, but it contains increased amounts of urinary intestinal-like AP.
Cephamandol 6.0 g, cephazolin 6.0 g or cephacetrile or cephalothin 8.0 g were administered as short-term infusions on 3 consecutive days to informed volunteers, who had no history or evidence of impairment of renal function. There were 15 subjects in the cephamandol, cephacetrile and cephalothin groups and 14 subjects in the cephazolin group. Alanine-aminopeptidase, a characteristic tubule enzyme, was determined in a 24-hour urine 2 days before administration, during the 3 day administration and on the 4 subsequent days. In addition, alanine-aminopeptidase was also estimated immunologically in concentrated urine with the aid of an anti-brush border antibody. Cephamandol, cephazolin and cephalothin were completely without effect on the proximal tubule. Cephacetrile, on the other hand, showed clear reactions in 9 out of 15 subjects, in the form of elevated AAP activity in urine and in 6 of the cases membrane elimination was demonstrable immunologically. After withdrawal of the medication, the values of the responder group returned spontaneously to normal, i.e. no cumulative effect was detected. These investigations show that elimination of alanine-aminopeptidase in the urine is a very sensitive index of the action of cephalosporins on renal tubules.
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