Small increases in the urinary excretion of glutathione S-transferase A1 and P1 after cardiac surgery are not associated with clinically relevant renal injury

Eijkenboom, J.; Eijk, L.T.G.J. van; Pickkers, Peter; Peters, Wilbert H.M.; Wetzels, Jack F.M.; Hoeven, Hans G. van der

doi:10.1007/s00134-005-2608-2

Cited by 33 publications

(13 citation statements)

References 13 publications

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“…At high specificities, !-and :-GST showed high sensitivity for predicting ARF and the need for renal replacement therapy in prospective studies on critically ill or renal patients (17,20). Excretion of the enzymes after major vascular and cardiac surgery and after renal transplantation has been described (21,22). Enzymuria seemed highly sensitive for renal tubular injury and to directly correlate with a rise in serum creatinine and fall in clearance, but the predictive value for ARF was relatively poor (21Y 25).…”

Section: Urinary Enzymesmentioning

confidence: 96%

Biomarkers of Acute Renal Injury and Renal Failure

Trof

Maggio

Leemreis

et al. 2006

Shock

179

101

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Acute renal failure (ARF) is a frequent problem in the intensive care unit and is associated with a high mortality. Early recognition could help clinical management, but current indices lack sufficient predictive value for ARF. Therefore, there might be a need for biomarkers in detecting renal tubular injury and/or dysfunction at an early stage before a decline in glomerular filtration rate is noted by an increased serum creatinine. A MEDLINE/PubMed search was performed, including all articles about biomarkers for ARF. All publication types, human and animal studies, or subsets were searched in English language. An extraction of relevant articles was made for the purpose of this narrative review. These biomarkers include tubular enzymes (alpha- and pi-glutathione S-transferase, N-acetyl-glucosaminidase, alkaline phosphatase, gamma-glutamyl transpeptidase, Ala-(Leu-Gly)-aminopeptidase, and fructose-1,6-biphosphatase), low-molecular weight urinary proteins (alpha1- and beta2-microglobulin, retinol-binding protein, adenosine deaminase-binding protein, and cystatin C), Na+/H+ exchanger, neutrophil gelatinase-associated lipocalin, cysteine-rich protein 61, kidney injury molecule 1, urinary interleukins/adhesion molecules, and markers of glomerular filtration such as proatrial natriuretic peptide (1-98) and cystatin C. These biomarkers, detected in urine or serum shortly after tubular injury, have been suggested to contribute to prediction of ARF and need for renal replacement therapy. However, excretion of these biomarkers may also increase after reversible and mild dysfunction and may not necessarily be associated with persistent or irreversible damage. Large prospective studies in human are needed to demonstrate an improved outcome of biomarker-driven management of the patient at risk for ARF.

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Section: Urinary Enzymesmentioning

confidence: 96%

Biomarkers of Acute Renal Injury and Renal Failure

Trof

Maggio

Leemreis

et al. 2006

Shock

179

101

View full text Add to dashboard Cite

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“…The risk of such a study design, however, is the identification of biomarkers that are too sensitive to be of clinical use. Tubular enzymes such as N-acetyl-b-(D)-glucosaminidase as well as a-glutathione and p-glutathione S-transferases, for example, are known to be elevated in the urine after cardiac surgery [39][40][41] but have not been adopted (perhaps inappropriately) into clinical practice because of concerns regarding possible nonspecificity of the appearance of tubular enzymes in the urine. Nevertheless, these types of studies may be useful to identify biomarkers that fulfill the vision put forth by the US Food and Drug Administration regarding qualification and use of biomarkers in drug development, dose regulation, and clinical monitoring of nephrotoxic drug exposure.…”

Section: Non-creatinine-based Endpoints For Biomarker Studiesmentioning

confidence: 99%

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

Waikar

Betensky

Emerson

et al. 2012

Journal of the American Society of Nephrology

253

200

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Clinicians have used serum creatinine in diagnostic testing for acute kidney injury for decades, despite its imperfect sensitivity and specificity. Novel tubular injury biomarkers may revolutionize the diagnosis of acute kidney injury; however, even if a novel tubular injury biomarker is 100% sensitive and 100% specific, it may appear inaccurate when using serum creatinine as the gold standard. Acute kidney injury, as defined by serum creatinine, may not reflect tubular injury, and the absence of changes in serum creatinine does not assure the absence of tubular injury. In general, the apparent diagnostic performance of a biomarker depends not only on its ability to detect injury, but also on disease prevalence and the sensitivity and specificity of the imperfect gold standard. Assuming that, at a certain cutoff value, serum creatinine is 80% sensitive and 90% specific and disease prevalence is 10%, a new perfect biomarker with a true 100% sensitivity may seem to have only 47% sensitivity compared with serum creatinine as the gold standard. Minimizing misclassification by using more strict criteria to diagnose acute kidney injury will reduce the error when evaluating the performance of a biomarker under investigation. Apparent diagnostic errors using a new biomarker may be a reflection of errors in the imperfect gold standard itself, rather than poor performance of the biomarker. The results of this study suggest that small changes in serum creatinine alone should not be used to define acute kidney injury in biomarker or interventional studies.

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“…Some authors have suggested that tubular enzymes are overly sensitive because they tend to rise after injuries such as CPB without an associated rise in SCr (85,86). While tubular enzymes may not prove to be particularly valuable biomarkers, it is unclear that a change in SCr is a satisfactory standard against which to judge their merit.…”

Section: Tubular Enzymes and Markers Of Tubular Dysfunctionmentioning

confidence: 99%

Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury

Waikar

Liu

Chertow

2008

Clinical Journal of the American Society of Nephrology

456

311

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Acute kidney injury is an increasingly common and potentially catastrophic complication in hospitalized patients. Early observational studies from the 1980s and 1990s established the general epidemiologic features of acute kidney injury: the incidence, prognostic significance, and predisposing medical and surgical conditions. Recent multicenter observational cohorts and administrative databases have enhanced our understanding of the overall disease burden of acute kidney injury and trends in its epidemiology. An increasing number of clinical studies focusing on specific types of acute kidney injury (e.g., in the setting of intravenous contrast, sepsis, and major surgery) have provided further details into this heterogeneous syndrome. Despite our sophisticated understanding of the epidemiology and pathobiology of acute kidney injury, current prevention strategies are inadequate and current treatment options outside of renal replacement therapy are nonexistent. This failure to innovate may be due in part to a diagnostic approach that has stagnated for decades and continues to rely on markers of glomerular filtration (blood urea nitrogen and creatinine) that are neither sensitive nor specific. There has been increasing interest in the identification and validation of novel biomarkers of acute kidney injury that may permit earlier and more accurate diagnosis. This review summarizes the major epidemiologic studies of acute kidney injury and efforts to modernize the approach to its diagnosis.

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Small increases in the urinary excretion of glutathione S-transferase A1 and P1 after cardiac surgery are not associated with clinically relevant renal injury

Cited by 33 publications

References 13 publications

Biomarkers of Acute Renal Injury and Renal Failure

Biomarkers of Acute Renal Injury and Renal Failure

Imperfect Gold Standards for Kidney Injury Biomarker Evaluation

Diagnosis, Epidemiology and Outcomes of Acute Kidney Injury

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