HETEROGENEITY OF GLUTATHIONE-S-TRANSFERASE ISOENZYME EXPRESSION IN RENAL-DISEASE

Recent work has suggested that glutathione S-transferase (GST) enzymuria may be used to assess renal injury in transplant kidneys. There is little work investigating the possibility of using glutathione S-transferase enzymuria to assess other renal diseases and this study was undertaken to evaluate the localisation of GST isoenzymes in various glomerular and tubular pathologies so that the specificity of these enzymes as markers of tubular injury could be defined. Immunostaining was carried out to establish the location of alpha and pi class GST in renal biopsies from patients with a wide variety of renal diseases including membranous glomerulonephritis, minimal-lesion glomerulonephritis, mesangial proliferative glomerulonephritis, loin pain haematuria syndrome, and renal allograft rejection. In the cases of glomerulonephritis studied, alpha class GST was detected in proximal tubules and pi class GST in distal convoluted tubules, podocytes, and Bowman's capsule. The majority of cases of glomerulonephritis showed a heterogeneous pattern of expression of both isoenzymes: that is, there was variation in intensity of staining both in single tubules and also between tubules as opposed to the uniform staining pattern observed in normal kidneys. The location of enzymes in the cases of glomerulonephritis was the same as that in normal kidneys and we were unable to demonstrate any de novo expression of GST isoenzymes. However, seven out of ten renal allograft biopsies showed expression of pi class GST in proximal tubules which were atrophic. Provided there is no significant tubular atrophy, urinary release of these enzymes may be used to localise renal tubular injury. In view of the role of GST isoenzymes in leukotriene and oxygen radical scavenger mechanisms the heterogeneity that we have demonstrated may be of importance.