A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde

Fonseca, Isabel; Reguengo, Henrique; Oliveira, José Carlos; Martins, La Salete; Malheiro, Jorge; Almeida, Manuela; Santos, Josefina; Dias, Leonídio; Pedroso, Sofía; Lobato, Luísa; Henriques, António Castro; Mendonça, Denisa

doi:10.1016/j.clinbiochem.2015.07.007

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…Recently, NGAL blood levels taken from brain-dead kidney donors prior to kidney graft harvesting could not predict the development of delayed graft function [20]. Additionally, the idea of combining several biomarkers to detect delayed graft function was proposed, with a possible triple biomarker approach of serum malondialdehyde, cystatin C, and creatinine [21].…”

Section: Discussionmentioning

confidence: 99%

Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation

Wijermars

Schaapherder

George

et al. 2018

Oxidative Medicine and Cellular Longevity

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Delayed graft function is an early complication following kidney transplantation with an unclear molecular mechanism. Here we determined whether impaired reactive aldehyde metabolism is associated with delayed graft function. Human kidney biopsies from grafts with delayed graft function were compared with grafts that did not develop delayed graft function by Ingenuity gene pathway analysis. A second series of grafts with delayed graft function (n = 10) were compared to grafts that did not develop delayed graft function (n = 10) by measuring reactive aldehyde metabolism, reactive aldehyde-induced protein adduct formation, and aldehyde dehydrogenase (ALDH) gene and protein expression. In the first series of kidney biopsies, several gene families known for metabolizing reactive aldehydes, such as aldehyde dehydrogenase (ALDH), aldo-keto reductase (AKR), and glutathione-S transferase (GSTA), were upregulated in kidneys that did not develop delayed graft function versus those that did. In the second series of kidney grafts, we focused on measuring aldehyde-induced protein adducts and ALDH enzymatic activity. The reactive aldehyde metabolism by ALDH enzymes was reduced in kidneys with delayed graft function compared to those that did not (37 ± 12∗ vs. 79 ± 5 μg/min/mg tissue, ∗ P < 0.005, respectively). ALDH enzymatic activity was also negatively correlated with length of hospital stay after a kidney transplant. Together, our study identifies a reduced ALDH enzymatic activity with kidneys developing delayed graft function compared to those that did not. Measuring ALDH enzymatic activity and reactive aldehyde-induced protein adducts can potentially be further developed as a biomarker to assess for delayed graft function and recovery from a kidney transplant.

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Section: Discussionmentioning

confidence: 99%

Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation

Wijermars

Schaapherder

George

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Evidence that other biomarkers of kidney damage, such as kidney injury molecule‐1 (KIM‐1) or liver‐type fatty‐acid‐binding protein (L‐FABP), is inconclusive. Further possible markers under assessment include the glycoprotein clusterin, the phosphoprotein osteopontin and the tumor necrosis factor α (TNF‐α) gene A20, markers of cell cycle arrest and inflammation, combinations of conventional and novel markers (e.g., creatinine, cystatin C, and malondialdehyde), T reg cell counts, and biomarkers obtained from hypothermic machine perfusion …”

Section: Prediction Of Dgfmentioning

confidence: 99%

Prediction, prevention, and management of delayed graft function: where are we now?

Nashan

Abbud-Filho

Citterio

2016

Clinical Transplantation

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Delayed graft function (DGF) remains a major barrier to improved outcomes after kidney transplantation. High-risk transplant recipients can be identified, but no definitive prediction model exists. Novel biomarkers to predict DGF in the first hours post-transplant, such as neutrophil gelatinase-associated lipocalin (NGAL), are under investigation. Donor management to minimize the profound physiological consequences of brain death is highly complex. A hormonal resuscitation package to manage the catecholamine "storm" that follows brain death is recommended. Donor pretreatment with dopamine prior to procurement lowers the rate of DGF. Hypothermic machine perfusion may offer a significant reduction in the rate of DGF vs simple cold storage, but costs need to be evaluated. Surgically, reducing warm ischemia time may be advantageous. Research into recipient preconditioning options has so far not generated clinically helpful interventions. Diagnostic criteria for DGF vary, but requirement for dialysis and/or persistent high serum creatinine is likely to remain key to diagnosis until current work on early biomarkers has progressed further. Management centers on close monitoring of graft (non)function and physiological parameters. With so many unanswered questions, substantial reductions in the toll of DGF in the near future seem unlikely but concentrated research on many levels offers long-term promise.

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“…In addition, strategies to increase SOD activity with recombinant SOD molecules and gene transfer led to reduced inflammation and oxidative stress in experimental models of ischemia–reperfusion and contrast-induced AKI [ 19 – 21 ]. It is also interesting to observe that in patients submitted to kidney transplantation, MDA levels were predictors of graft dysfunction [ 22 , 23 ]. Despite the importance of oxidative stress, SOD1 activity has not yet been evaluated as predictor of AKI in patients with septic shock.…”

Section: Introductionmentioning

confidence: 99%

Erythrocyte superoxide dismutase as a biomarker of septic acute kidney injury

Costa

Gut

Azevedo

et al. 2016

Ann. Intensive Care

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Background Oxidative stress is a key feature of sepsis and could be a common pathophysiological pathway between septic shock and acute kidney injury (AKI) Our objective was to evaluate the erythrocyte superoxide dismutase (SOD1) activity as predictor of AKI in patients with septic shock.MethodsThis is a prospective observational study that evaluated 175 consecutive patients over the age of 18 years with septic shock upon intensive care unit (ICU) admission. However, 43 patients were excluded (27 due to AKI at ICU admission). Thus, 132 patients were enrolled in the study. At the time of the patients’ enrollment, demographic information was recorded. Blood samples were taken within the first 24 h of the patient’s admission to determine the erythrocyte SOD1 activity. All patients were followed throughout the ICU stay, and the development of AKI was evaluated. In addition, we also evaluated 17 control subjects.ResultsThe mean age of patients with septic shock was 63.2 ± 15.7 years, 53 % were male and the median ICU stay was 8 days (4–16). Approximately 50.7 % developed AKI during the ICU stay. The median erythrocyte SOD1 activity was 2.92 (2.19–3.92) U/mg Hb. When compared to control subjects, septic shock patients had a higher serum malondialdehyde concentration and lower erythrocyte SOD1 activity. In univariate analysis, erythrocyte SOD1 activity was lower in patients who developed AKI. The ROC curve analysis revealed that lower erythrocyte SOD1 activity was associated with AKI development (AUC 0.686; CI 95 % 0.595–0.777; p < 0.001) at the cutoff of <3.32 U/mg Hb. In the logistic regression models, SOD1 activity higher than 3.32 U/mg Hb was associated with protection of AKI development when adjusted by hemoglobin, phosphorus and APACHE II score (OR 0.309; CI 95 % 0.137–0.695; p = 0.005) and when adjusted by age, gender, chronic kidney disease, admission category (medical or surgery) and APACHE II score (OR 0.129; CI 95 % 0.033–0.508; p = 0.003).ConclusionsIn conclusion, our data suggest that erythrocyte SOD1 activity could play a role as an early marker of septic AKI and could be seen as a new research avenue in the field of biomarker in AKI. However, our study did not show a strong correlation between SOD activity and AKI. Nevertheless, these original data do warrant further research in order to confirm or not this hypothesis.

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A triple-biomarker approach for the detection of delayed graft function after kidney transplantation using serum creatinine, cystatin C, and malondialdehyde

Abstract: A combination of graft damage biomarkers outperformed SCr in the early diagnosis of DGF, and the best performance was achieved by a triple-marker approach, using SCr, MDA, and CysC.

Cited by 17 publications

References 34 publications

Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation

Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation

Prediction, prevention, and management of delayed graft function: where are we now?

Erythrocyte superoxide dismutase as a biomarker of septic acute kidney injury

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