RESULTSAll three patients with rejection episodes showed GGTP elevation, On the first patient who had two rejection episodes, plasma GGTP elevation preceded each. On the second and third patients, GGTP elevation coincided with the onset of rejection.Of the 14 patients investigated, all but two were found to have raised plasma GGTP levels at some stage during the course of the investigation. On the majority of these, enzyme levels did not exceed twice the upper limit of normal. Three patients had graft rejection episodes. One of these patients had a second episode of rejection. Rejection was generally considered to have occurred when there was a simultaneous fall in urine output, rise in plasma creatinine and blood urea levels and clinical deterioration. Two patients died during the course of the study.The possible influence of transplant rejection, low urine output, dialysis, azathioprine administration infection and surgery on plasma GGTP levels was considered. The effect of these factors is shown in Tables 1 and 2 and considered below. In the tables a rise in GGTP activity is defined as a change in GGTP levels exceeding 30 i.u./1 persisting for more than 24 h. A change of this magnitude having been found to exceed normal day-to-day variation in serum enzyme activity. Where pre-transplant GGTP levels were not available, transplantation was considered to have resulted in a rise in GGTP if the enzyme was elevated at the initial determination.
Effect of low urine outputUrine output was reduced for at least 48 h to between 500 and 1,000 ml/24 h on eight occasions in four patients. On only two occasions did GGTP elevation result. Urine output was reduced to less than 500 ml in nine patients, and a rise in plasma GGTP levels was observed in five of these. This rise, was, however, coincident with graft rejection in two patients and in the post-transplant period in a third.
MATERIALS AND METHODSGGTP was determined by a method described in detail elsewhere (Rosalki et al., 1970) using L-yglutamyl-p-nitroanilide as substrate and glycylglycine as glutamyl group acceptor. The upper limit of normal of plasma GGTP activity is 60 i.u./1 at 37°C for males and 50 i.u./1 at 37°C for females.Fourteen renal transplant patients wereavailable for investigation, and these were followed for some three months following cadaveric renal transplantation. Plasma GGTP levels were determined on specimens obtained six days a week in the month following transplantation, and thereafter bi-weekly or at more frequent intervals depending on the clinical Transplant rejection state. Glutamate-oxaloacetate transaminase, and glutamate-pyruvate transaminase determinations (Reitman and Frankel, 1957) were carried out on many of the samples that showed raised GGTP levels. On some samples GGTP isoenzymes were examined after separation by electrophoresis on cellulose acetate membrane. Isoenzymes were demonstrated by a staining procedure similar to that previously described for leucine aminopeptidase isoenzymes (Meade and Rosalki, 1964), but substituting y-...