scholarly journals Validation of a commercial magnetic bead–based multiplex assay for 5 novel biomarkers of acute kidney injury in canine serum

2020 ◽  
Vol 32 (5) ◽  
pp. 656-663
Author(s):  
Jennifer Davis ◽  
Anthea L. Raisis ◽  
David W. Miller ◽  
Gabriele Rossi
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Cost Effective ◽  
Magnetic Bead ◽  
Sample Type ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Novel Biomarkers ◽  
Canine Serum ◽  
Kidney Injury Molecule 1

Interest is growing in measurement of novel biomarkers for the diagnosis of acute kidney injury. Multiplex assays may provide a rapid and cost-effective way of measurement; however, sparse information is published regarding their use in dogs. We aimed to validate a commercial magnetic bead–based assay for 5 biomarkers: clusterin (Clus), cystatin C (CysC), kidney injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 (MCP-1), and neutrophil gelatinase–associated lipocalin (NGAL). Intra- and inter-assay imprecision, linearity under dilution (LUD), spike recovery (S-R), and hemoglobin interference were evaluated using serum from healthy and diseased dogs. Additionally, the effect of sample type (serum vs. plasma) was investigated. All values for Clus and MCP-1 were outside the assay’s measurable range. Intra- and inter-assay precision were acceptable for NGAL (CVs 8.8% and 13.2%, respectively). Regression analysis of LUD and S-R indicated good linearity for CysC and NGAL. Hemolysis did not affect measurement of any biomarker. Measured concentrations of CysC ( p = 0.018) and NGAL ( p = 0.015) were significantly lower in sodium citrate plasma compared to serum. We conclude that this magnetic bead–based assay is precise and accurate for NGAL measurement in canine serum. Inappropriate standards for MCP-1 and Clus, and poor accuracy for KIM-1 measurement, suggest that this assay cannot reliably quantify those biomarkers in canine blood. Measurements of CysC in canine blood using this assay must be interpreted with caution given inter-assay imprecision.

scholarly journals Tubulointerstitial Biomarkers for Diabetic Nephropathy

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Bancha Satirapoj
Keyword(s):  
Diabetic Nephropathy ◽  
Tissue Injury ◽  
Kidney Injury ◽  
Cardiovascular Complications ◽  
Renal Tissue ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Potential Applications ◽  
Novel Biomarkers ◽  
Kidney Injury Molecule 1

Patients with diabetic nephropathy have a higher risk of mortality, mostly from cardiovascular complications. Standard biomarkers including serum creatinine, estimated glomerular filtration rate, and albuminuria are imprecise, do not directly measure renal tissue injury, and are relatively insensitive to small changes in renal function. Thus, availability of novel biomarkers that are sensitive, specific, and precise as well as able to detect kidney injury and predict clinically significant outcomes would be widely useful in diabetic nephropathy. Novel biomarkers of the processes that induce tubulointerstitial changes may ultimately prove to better predict renal progression and prognosis in type 2 diabetes. Recently, certain biomarkers, which were initially identified in acute kidney injury, also have been reported to confer value in evaluating patients with chronic kidney disease. Biomarkers such as cystatin C, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), angiotensinogen, periostin, and monocyte chemoattractant protein-1 (MCP-1) reflect tubular injury. In this article, we focused on the potential applications of these biomarkers in diabetic nephropathy.

scholarly journals Postangiography Increases in Serum Creatinine and Biomarkers of Injury and Repair

2020 ◽  
Vol 15 (9) ◽  
pp. 1240-1250 ◽  
Author(s):  
Caroline Liu ◽  
Maria K. Mor ◽  
Paul M. Palevsky ◽  
James S. Kaufman ◽  
Heather Thiessen Philbrook ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Serious Adverse Events ◽  
Monocyte Chemoattractant Protein 1 ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Iodinated Contrast ◽  
Injury And Repair ◽  
Kidney Injury Molecule 1 ◽  
Major Adverse Kidney Events

Background and objectivesIt is unknown whether iodinated contrast causes kidney parenchymal damage. Biomarkers that are more specific to nephron injury than serum creatinine may provide insight into whether contrast-associated AKI reflects tubular damage. We assessed the association between biomarker changes after contrast angiography with contrast-associated AKI and 90-day major adverse kidney events and death.Design, setting, participants, & measurementsWe conducted a longitudinal analysis of participants from the biomarker substudy of the Prevention of Serious Adverse Events following Angiography trial. We measured injury (kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, IL-18) and repair (monocyte chemoattractant protein-1, uromodulin, YKL-40) proteins from plasma and urine samples at baseline and 2–4 hours postangiography. We assessed the associations between absolute changes and relative ratios of biomarkers with contrast-associated AKI and 90-day major adverse kidney events and death.ResultsParticipants (n=922) were predominately men (97%) with diabetes (82%). Mean age was 70±8 years, and eGFR was 48±13 ml/min per 1.73 m2; 73 (8%) and 60 (7%) participants experienced contrast-associated AKI and 90-day major adverse kidney events and death, respectively. No postangiography urine biomarkers were associated with contrast-associated AKI. Postangiography plasma kidney injury molecule-1 and IL-18 were significantly higher in participants with contrast-associated AKI compared with those who did not develop contrast-associated AKI: 428 (248, 745) versus 306 (179, 567) mg/dl; P=0.04 and 325 (247, 422) versus 280 (212, 366) mg/dl; P=0.009, respectively. The majority of patients did not experience an increase in urine or plasma biomarkers. Absolute changes in plasma IL-18 were comparable in participants with contrast-associated AKI (−30 [−71, −9] mg/dl) and those without contrast-associated AKI (−27 [−53, −10] mg/dl; P=0.62). Relative ratios of plasma IL-18 were also comparable in participants with contrast-associated AKI (0.91; 0.86, 0.97) and those without contrast-associated AKI (0.91; 0.85, 0.96; P=0.54).ConclusionsThe lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.

scholarly journals Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy

2017 ◽  
Vol 243 (3) ◽  
pp. 272-282 ◽  
Author(s):  
Blessy George ◽  
Melanie S Joy ◽  
Lauren M Aleksunes
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Urinary Proteins ◽  
Protein Biomarkers ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Chemotactic Protein ◽  
Trefoil Factor 3 ◽  
Beta 2 Microglobulin ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Despite recent progress in the development of novel approaches to treat cancer, traditional antineoplastic drugs, such as cisplatin, remain a mainstay of regimens targeting solid tumors. Use of cisplatin is limited by acute kidney injury, which occurs in approximately 30% of patients. Current clinical measures, such as serum creatinine and estimated glomerular filtration rate, are inadequate in their ability to detect acute kidney injury, particularly when there is only a moderate degree of injury. Thus, there is an urgent need for improved diagnostic biomarkers to predict nephrotoxicity. There is also interest by the U.S. Food and Drug Administration to validate and implement new biomarkers to identify clinical and subclinical acute kidney injury in patients during the drug approval process. This minireview provides an overview of the current literature regarding the utility of urinary proteins (albumin, beta-2-microglobulin, N-acetyl-D-glucosaminidase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and cystatin C) as biomarkers for cisplatin-induced AKI. Many of the well-studied urinary proteins (KIM-1, NGAL, B2M, albumin) as well as emerging biomarkers (calbindin, monocyte chemotactic protein-1, and trefoil factor 3) display distinct patterns of time-dependent excretion after cisplatin administration. Implementation of these biomarker proteins in the oncology clinic has been hampered by a lack of validation studies. To address these issues, large head-to-head studies are needed to fully characterize time-dependent responses and establish accurate cutoff values and ranges, particularly in cancer patients. Impact statement There is growing interest in using urinary protein biomarkers to detect acute kidney injury in oncology patients prescribed the nephrotoxic anticancer drug cisplatin. We aim to synthesize and organize the existing literature on biomarkers examined clinically in patients receiving cisplatin-containing chemotherapy regimens. This minireview highlights several proteins (kidney injury molecule-1, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, calbindin, monocyte chemotactic protein-1, trefoil factor 3) with the greatest promise for detecting cisplatin-induced acute kidney injury in humans. A comprehensive review of the existing literature may aid in the design of larger studies needed to implement the clinical use of these urinary proteins as biomarkers of kidney injury.

scholarly journals Screening of early diagnostic markers of gentamicin-induced acute kidney injury in canines

2019 ◽  
Vol 63 (3) ◽  
pp. 405-411
Author(s):  
Jia-San Zheng ◽  
Jing-Nie ◽  
Ting-Ting Zhu ◽  
Hong-Ri Ruan ◽  
Xue-Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Characteristic Curve ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Fatty Acid Binding ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Transmission Electron ◽  
Renal Tubular ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Abstract Introduction The value of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (Kim-1), and liver-type fatty acid binding protein (L-FABP) was assessed in early diagnosis of gentamicin-induced acute kidney injury (AKI) in dogs. Material and Methods Subcutaneous gentamicin injection in 16 healthy adult beagles made the AKI model. Blood was sampled every 6 h to detect NGAL, Kim-1, L-FABP, and serum creatinine (SCr) concentrations. Kidney tissue of two dogs was taken before the injection, as soon as SCr was elevated (78 μmol/L), and when it had risen to 1.5 times the baseline, and haematoxylin-eosin staining and transmission electron microscopy (TEM) were used to observe changes. Results NGAL, Kim-1, and SCr levels were significantly increased (P < 0.05) at 18, 30, and 78 h post injection, but L-FABP concentration was not associated with renal injury. At the earliest SCr elevation stage, findings were mild oedema, degeneration, and vacuolisation in renal tubular epithelial cells in pathology, and mild cytoplasmic and mitochondrial oedema in TEM. At this time point, NGAL and Kim-1 concentrations were significantly increased (P < 0.05), indicating that these two molecules biomark early kidney injury in dogs. Using receiver operating characteristic curve analysis, their warning levels were > 25.31 ng/mL and > 48.52 pg/mL. Conclusion Plasma NGAL and Kim-1 above warning levels are early indicators of gentamicin-induced AKI in dogs.

scholarly journals Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004802021
Author(s):  
Kelly R. McMahon ◽  
Hayton Chui ◽  
Shahrad Rod Rassekh ◽  
Kirk R. Schultz ◽  
Tom D. Blydt-Hansen ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hospital Discharge ◽  
Characteristic Curve ◽  
Kidney Injury ◽  
Urine Ngal ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Post Infusion ◽  
Kidney Injury Molecule 1 ◽  
Stage 1 ◽  
Neutrophil Gelatinase

Background: Few studies have described associations between acute kidney injury (AKI) biomarkers, urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1), and AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Methods: Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin based on Kidney Disease: Improving Global Outcomes guidelines criteria (≥stage 1). Results: Of 159 children, 156 (median [interquartile (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty-six of 156 (29%) and 22/127 (17%) developed AKI within 10 days of cisplatin administration following early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with vs. without AKI (near hospital discharge of late cisplatin infusion, median [IQR]: NGAL: 76.1 [10.0-232.7] vs. 14.9 [5.4-29.7] ng/mg creatinine; KIM-1: 4415 [2083-9077] vs. 1049 [358-3326] pg/mg creatinine; P<.01). These markers modestly discriminated for AKI (area under receiver-operating characteristic curve (AUC-ROC) range: NGAL: 0.56-0.72; KIM-1: 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROCs range: 0.54-0.75) vs. early infusions (AUC-ROCs range: 0.48-0.65). Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and late kidney outcomes associations.

scholarly journals Biomarkers of Acute Kidney Injury after Cardiac Surgery: A Narrative Review

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Binbin Wu ◽  
Jianghua Chen ◽  
Yi Yang
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Injury ◽  
High Sensitivity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Cycle Arrest ◽  
Diagnostic Standards ◽  
Novel Biomarkers ◽  
Diagnostic Capabilities ◽  
Neutrophil Gelatinase

Cardiac surgery-associated acute kidney injury (CSA-AKI) is a major and serious complication in patients undergoing cardiac surgery and is independently associated with perioperative mortality and mortality. Therapeutic intervention aiming at reversing kidney dysfunction seems disappointing across multiple settings. Consequently, attention has shifted from treatment to prevention and early detection. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines have unified diagnostic standards mainly based on the serum creatinine (Scr) level or urine output, but neither marker is kidney specific. Efforts have been made to identify novel biomarkers with high sensitivity and specificity. The diagnostic capabilities of neutrophil gelatinase-associated lipocalin (NGAL) and G1 cell cycle arrest biomarker as biomarkers have been confirmed in a large number of clinical trials. The utility of biomarkers of cardiac function and inflammation has been validated in clinical studies. Aiming to offer valuable information for further research, we summarize the progress in defining current markers relevant to CSA-AKI in the last three years.

scholarly journals A Novel Biomarker for Acute Kidney Injury, Vanin-1, for Obstructive Nephropathy: A Prospective Cohort Pilot Study

2019 ◽  
Vol 20 (4) ◽  
pp. 899 ◽  
Author(s):  
Satoshi Washino ◽  
Keiko Hosohata ◽  
Masashi Oshima ◽  
Tomohisa Okochi ◽  
Tsuzumi Konishi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Obstructive Nephropathy ◽  
Control Group ◽  
Operating Characteristics ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Receiver Operating Characteristics Curve ◽  
Kidney Injury Molecule 1 ◽  
Neutrophil Gelatinase

Background: Vanin-1 is a novel acute kidney injury (AKI) biomarker that has not been clinically investigated as a biomarker for obstructive nephropathy. This study investigated the diagnostic value of vanin-1 as a biomarker for adult obstructive nephropathy by comparing it to existing AKI biomarkers. Methods: A total of 49 patients, 21 controls, and 28 hydronephrosis (HN) cases were assessed. AKI biomarkers in bladder (BL) urine and renal pelvic (RP) urine in the HN group were compared to each BL marker in the control group. In a subgroup of cases receiving interventions for obstructive nephropathy, the BL values of each biomarker were assessed after the intervention. Results: RP vanin-1 levels were significantly higher while BL vanin-1 levels were marginally higher in the HN group than in the control group. The area under the receiver operating characteristics curve values for RP and BL vanin-1 were 0.9778 and 0.6386, respectively. In multivariate analyses, BL vanin-1 and N-acetyl-β-D-glucosaminidase (NAG), but not kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL), were independent factors for predicting the presence of HN. In cases receiving interventions, vanin-1 decreased significantly from 1 week after the intervention in cases of moderate to severe obstructive nephropathy compared to RP values at baseline. Conclusion: Urinary vanin-1 is a useful biomarker to detect and monitor the clinical course of obstructive nephropathy.

Sign in / Sign up

Export Citation Format

Share Document