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

McMahon, Blaithin A.; Koyner, Jay L.; Murray, Patrick

doi:10.1097/mcc.0b013e32833fdd9a

Cited by 31 publications

(16 citation statements)

References 30 publications

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“…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).…”

Section: Increased Urinary Iron and Transferrin Excretion In Patientsmentioning

confidence: 89%

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

Raaij

Rennings

Biemond

et al. 2019

American Journal of Physiology-Renal Physiology

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In physiological conditions, circulating iron can be filtered by the glomerulus and is almost completely reabsorbed by the tubular epithelium to prevent urinary iron wasting. Increased urinary iron concentrations have been associated with renal injury. However, it is not clear whether increased urinary iron concentrations in patients are the result of increased glomerular iron filtration and/or insufficient tubular iron reabsorption and if these processes contribute to renal injury. We measured plasma and urine iron parameters and urinary tubular injury markers in healthy human subjects ( n = 20), patients with systemic iron overload ( n = 20), and patients with renal tubular dysfunction ( n = 18). Urinary iron excretion parameters were increased in both patients with systemic iron overload and tubular dysfunction, whereas plasma iron parameters were only increased in patients with systemic iron overload. In patients with systemic iron overload, increased urinary iron levels were associated with elevated circulating iron, as indicated by transferrin saturation (TSAT), and increased body iron, as suggested by plasma ferritin concentrations. In patients with tubular dysfunction, enhanced urinary iron and transferrin excretion were associated with distal tubular injury as indicated by increased urinary glutathione S-transferase pi 1-1 (GSTP1-1) excretion. In systemic iron overload, elevated urinary iron and transferrin levels were associated with increased injury to proximal tubules, indicated by increased urinary kidney injury marker 1 (KIM-1) excretion. Our explorative study demonstrates that both glomerular filtration of elevated plasma iron levels and insufficient tubular iron reabsorption could increase urinary iron excretion and cause renal injury.

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Section: Increased Urinary Iron and Transferrin Excretion In Patientsmentioning

confidence: 89%

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

Raaij

Rennings

Biemond

et al. 2019

American Journal of Physiology-Renal Physiology

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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BackgroundBiomarkers are potentially useful in assessment of outcomes in patients with cirrhosis, but information is very limited. Given the large number of biomarkers, adequate choice of which biomarker(s) to investigate first is important.AimAnalysis of potential usefulness of a panel of urinary biomarkers in outcome assessment in cirrhosis.Patients and MethodsFifty-five patients with acute decompensation of cirrhosis were studied: 39 had Acute Kidney Injury (AKI) (Prerenal 12, type-1 HRS (hepatorenal syndrome) 15 and Acute Tubular Necrosis (ATN) 12) and 16 acute decompensation without AKI. Thirty-four patients had Acute-on-chronic liver failure (ACLF). A panel of 12 urinary biomarkers was assessed, using a multiplex assay, for their relationship with ATN, ACLF and mortality.ResultsBiomarker with best accuracy for ATN diagnosis was NGAL (neutrophil-gelatinase associated lipocalin): 36 [26-125], 104 [58-208] and 1807 [494-3,716] μg/g creatinine in Prerenal-AKI, type-1 HRS and ATN, respectively; p<0.0001 (AUROC 0.957). Other attractive biomarkers for ATN diagnosis were IL-18, albumin, trefoil-factor-3 (TFF-3) and glutathione-S-transferase-π (GST-π) Biomarkers with less accuracy for ATN AUCROC<0.8 were β2-microglobulin, calbindin, cystatin-C, clusterin and KIM-1 (kidney injury molecule-1). For ACLF, the biomarker with the best accuracy was NGAL (ACLF vs. No-ACLF: 165 [67-676] and 32 [19-40] μg/g creatinine; respectively; p<0.0001; AUROC 0.878). Interestingly, other biomarkers with high accuracy for ACLF were osteopontin, albumin, and TFF-3. Biomarkers with best accuracy for prognosis were those associated with ACLF.ConclusionsA number of biomarkers appear promising for differential diagnosis between ATN and other types of AKI. The most interesting biomarkers for ACLF and prognosis are NGAL, osteopontin, albumin, and TFF-3. These results support the role of major inflammatory reaction in the pathogenesis of ACLF.

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“…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.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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Novel acute kidney injury (AKI) biomarkers offer promise of earlier diagnosis and risk stratification, but have yet to find widespread clinical application. We measured urinary a and glutathione S-transferases (a-GST and -GST), urinary L-type fatty acid-binding protein (L-FABP), urinary neutrophil gelatinase-associated lipocalin (NGAL), urinary hepcidin and serum cystatin c (CysC) before surgery, post-operatively and at 24 h after surgery in 93 high risk patient undergoing cardiopulmonary bypass (CPB) and assessed the ability of these biomarkers alone and in combination to predict RIFLE-R defined AKI in the first 5 post-operative days. Twenty-five patients developed AKI. Despite statistical significance in receiver-operator characteristic (ROC) analysis, when assessed by ability to define patients to two groups at high and low risk of AKI, combinations failed to significantly improve classification of risk compared to the best single biomarkers. In an alternative approach using Classification and Regression Tree (CART) analysis a model involving NGAL:Cr measurement post-op followed by Hepcidin:Cr at 24 h was developed which identified high, intermediate and low risk groups for AKI. Regression tree analysis has the potential produce models with greater clinical utility than single combined scores.

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

Cited by 31 publications

References 30 publications

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

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

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

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

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