Urinary glutathione S-transferases in the pathogenesis and diagnostic evaluation of acute kidney injury following cardiac surgery: a critical review

Abstract

Purpose of review A focused review of the nature, source, physiological role and rapidly expanding evidence for glutathione S-transferase (GST) subtypes π and α as biomarkers of acute kidney injury (AKI) in patients undergoing cardiac surgery. Expanded insights into the site-specific expression of the GSTs in defined parts of the nephron during renal damage are presented, with particular emphasis on the pathogenesis of cardiac surgery and cardiopulmonary bypass (CPB)-associated AKI and the role of GSTs in oxygen radical disposal. Recent findings Recent developments have highlighted a potential role of urinary α-GST and π-GST in the diagnostic evaluation of cardiac surgery-associated AKI. Both urinary α-GST and π-GST are detected in the postoperative period. π-GST performed best at predicting AKI severity at the time of the initial diagnosis of AKI. α-GST was able to predict the future development of both stage 1 and stage 3 AKI. Summary The current data from a small number of patients suggest a potential role of urinary GSTs in the clinical diagnostic evaluation of AKI following cardiac surgery. The performance of the GSTs for the early diagnosis of AKI needs to be validated in larger multicentre studies and in other patient populations at increased risk of AKI (e.g. patients with acute transplant rejection, septic patients). Comparison with other emerging AKI biomarkers is required to continue the development of π-GST and α-GST. Finally, additional studies examining the pathophysiological role of the GSTs in minimizing oxygen free radical exposure in the renal tubules during CPB may shed further light into their role as promising biomarkers of cardiac surgery-associated AKI.

Iron handling by the human kidney: glomerular filtration and tubular reabsorption both contribute to urinary iron excretion

“…We analyzed urinary iron and transferrin concentrations against KIM1 and GSTP1-1 to investigate the relation between iron excretion and PT and DT injury, respectively (34,35). Whereas we found no correlation between KIM1 and urinary iron or transferrin levels (Figure 2c, d), GSTP1-1 was positively associated with both iron and transferrin (r=0.56, p<0.05, and r=0.86, p<0.001, respectively; Figure 2e, f).…”

Analysis of a Urinary Biomarker Panel for Clinical Outcomes Assessment in Cirrhosis

“…GST-π belongs to the family of glutathione-S-transferases that are ubiquitous enzymes that act by detoxifying free radicals. They are present in a large variety of tissues, but the α and π isoforms are very abundant in kidney tubules and are overexpressed after kidney injury [ 27 ]. Evidence indicates that urinary GST-π levels are helpful for early diagnosis and predicting progression of ATN after cardiac surgery [ 28 ].…”

Combination of biomarkers for diagnosis of acute kidney injury after cardiopulmonary bypass

“…Co-investigators performing biomarker assays were blinded to patient details and AKI classification. We assessed four biomarkers of tubular injury: urinary α and π glutathione S -transferases (α-GST and π-GST), 17–19 urinary L-type fatty acid-binding protein (l-FABP) 20 and urinary NGAL, 5,21,22 and two biomarkers that potentially reflect changes in glomerular filtration: urinary hepcidin 23–25 and serum CysC. 11 We have reported on the utility of urinary hepcidin and NGAL for diagnosis of AKI in this study cohort previously.…”