Ajw. Branten et al., Urinary excretion of glutathione S transferases alpha and pi in patients with proteinuria: Reflection of the site of tubular injury, NEPHRON, 85(2), 2000, pp. 120-126
In patients with renal diseases, proteinuria is a major determinant of prog
ressive renal failure, probably by causing tubular cell injury. Little is k
nown on extent and site of tubular cell injury in patients with proteinuria
. Glutathione S transferases (GST) are cytosolic enzymes. The alpha isoform
is present only in proximal tubular cells, whereas the pi isoform is confi
ned to distal tubular cells. We have studied the urinary excretion of both
isoenzymes in 56 (38 male and 18 female) patients with glomerular diseases
and proteinuria. The mean age was 45 +/- (SD) 16 years, the median creatini
ne clearance was 80 (range 27-159) ml/min, and the median albuminuria was 4
.2 (range 0.7-16.9) g/10 mmol creatinine. The excretions of both GST alpha
(median 35.9 ng/10 mmol creatinine) and GST pi (median 24.8 ng/10 mmol crea
tinine) were elevated as compared with control values (upper limits 10 and
12 ng/10 mmol creatinine, respectively). The urinary excretion of GST pi, b
ut not that of GST alpha, was inversely correlated with the creatinine clea
rance. The highest levels of GST alpha were found in patients with a well-p
reserved renal function, whereas highest levels of GST pi were found in pat
ients with renal failure. In a small number of patients we performed immuno
fluorescent studies of renal tissue. An increased urinary excretion of GST
alpha correlated with brush border damage and decreased staining of proxima
l tubules for that isoenzyme. Our data suggest that in patients with protei
nuria initial injury is apparent at the proximal tubules. Measurements of G
ST alpha and GST pi appear useful to study longitudinal timing and site of
proteinuria-induced tubular cell injury. Copyright (C) 2000 S. Karger AG, B
asel.