Catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase in human cortical nephron segments: heterogeneous changes in acute renal failure and acute rejection following kidney allotransplantation.

Abstract

The catalytic activities of alkaline phosphatase and N-acetyl-beta-D-glucosaminidase, constituents of luminal brush-border membranes and lysosomes of kidney tubular cells, were measured in human kidney allografts in the maintenance and recovery phases of acute renal failure and in acute rejection crisis. The enzyme activities were fluorometrically determined in single microdissected cortical nephron segments of biopsies from 4 kidney allografts taken intraoperatively and postoperatively at different periods, which exhibited either good function or dysfunction. For comparison, the unaffected part of a human kidney nephrectomized due to hypernephroma as well as a biopsy of a morphologically normal human kidney were examined. Both enzymes displayed highest activities in the proximal part of the human nephron. In some intraoperative and postoperative biopsies with acute renal failure, alkaline phosphatase activity was reduced in proximal tubules, predominantly in the straight portion. This reduction could not be correlated with function. In acute rejection, very low alkaline phosphatase activities were uniformly found in proximal convoluted and straight tubules. Furthermore, intraoperative biopsies and biopsies of the functioning allograft have only approximately 50% of normal N-acetyl-beta-D-glucosaminidase activity in proximal convoluted tubules, but generally normal values in the straight portion. However, in acute renal failure, this enzyme activity was several-fold enhanced along the whole nephron, when compared with intraoperative values. In acute rejection, N-acetyl-beta-D-glucosaminidase activity was slightly reduced in proximal convoluted tubules, when compared with biopsies showing good function. It is suggested that the decrease of proximal tubular enzyme activities is the consequence of increased enzymuria and inadequate enzyme regeneration. On the other hand, the overshoot of N-acetyl-beta-D-glucosaminidase activity in the maintenance phase of acute renal failure appears to indicate increased degradative capacity, associated with cellular regeneration along the whole nephron.