ArticleKidney international2020
IL-6-mediated hepatocyte production is the primary source of plasma and urine neutrophil gelatinase-associated lipocalin during acute kidney injury.
Article in Kidney international, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Levels of circulating kidney injury markers and IL-10 identify non-critically ill patients with COVID-19 at risk of death.JCI insight · 2026Trial
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Human Liver Organoids as an Experimental Tool to Investigate Lipocalin-2 in Hepatic Inflammation.Cells · 2026Article
- Research advances on the gut-kidney axis theory in sepsis-associated acute kidney injury.Frontiers in pharmacology · 2026Review
- Fetuin-A and Heme Oxygenase 1 as Potential New Markers in the Diagnosis of Diabetic Kidney Disease.International journal of molecular sciences · 2025Review
- Serial Combination of Toxic and Ischemic Renal Damages Causes Subsequent Chronic, Irreversible, and Progressive Renal Disease in Rats.International journal of molecular sciences · 2025Article
- Effects of inflammation on hypoxic renal tubular epithelial cell injury under high-glucose conditions and the regulatory role of miR-125b.Scientific reports · 2025Article
- Evaluation of neutrophil gelatinase-associated lipocalin (NGAL) levels as a biomarker for the early diagnosis of heart failure patients without of kidney disease.Journal of cardiovascular and thoracic research · 2025Article
- Procalcitonin levels in septic and nonseptic subjects with AKI and ESKD prior to and during continuous kidney replacement therapy (CKRT).Critical care (London, England) · 2025Article
- mTOR promotes the formation and growth of tertiary lymphoid tissues in the kidney.Frontiers in immunology · 2025Article
- A Multi-Biomarker Approach to Increase the Accuracy of Diagnosis and Management of Coronary Artery Disease.Journal of cardiovascular development and disease · 2024Article
- Disruption in glutathione metabolism and altered energy production in the liver and kidney after ischemic acute kidney injury in mice.Scientific reports · 2024Article
- NGAL in the Development of Acute Kidney Injury in a Murine Model of Remote Ischaemic Preconditioning and Liver Ischaemia Reperfusion.International journal of molecular sciences · 2024Article
- Neutrophil Gelatinase-Associated Lipocalin as a Biomarker in Post-Acute COVID-19 Syndrome.Journal of clinical medicine · 2024Article
- Review of lipocalin-2-mediated effects in diabetic retinopathy.International ophthalmology · 2024Review
- Acute kidney injury biomarker olfactomedin 4 predicts furosemide responsiveness.Pediatric nephrology (Berlin, Germany) · 2023Article
- IL-6 mediates the hepatic acute phase response after prerenal azotemia in a clinically defined murine model.American journal of physiology. Renal physiology · 2023Article
- Article
- Identification of Pre-Renal and Intrinsic Acute Kidney Injury by Anamnestic and Biochemical Criteria: Distinct Association with Urinary Injury Biomarkers.International journal of molecular sciences · 2023Article
- Sustained release of drug-loaded nanoparticles from injectable hydrogels enables long-term control of macrophage phenotype.Biomaterials science · 2022Article
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15 authors at 7 institutions in 1 country.
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Abstract
Neutrophil gelatinase associated lipocalin (NGAL, Lcn2) is the most widely studied biomarker of acute kidney injury (AKI). Previous studies have demonstrated that NGAL is produced by the kidney and released into the urine and plasma. Consequently, NGAL is currently considered a tubule specific injury marker of AKI. However, the utility of NGAL to predict AKI has been variable suggesting that other mechanisms of production are present. IL-6 is a proinflammatory cytokine increased in plasma by two hours of AKI and mediates distant organ effects. Herein, we investigated the role of IL-6 in renal and extra-renal NGAL production. Wild type mice with ischemic AKI had increased plasma IL-6, increased hepatic NGAL mRNA, increased plasma NGAL, and increased urine NGAL; all reduced in IL-6 knockout mice. Intravenous IL-6 in normal mice increased hepatic NGAL mRNA, plasma NGAL and urine NGAL. In mice with hepatocyte specific NGAL deletion (Lcn2hep-/-) and ischemic AKI, hepatic NGAL mRNA was absent, and plasma and urine NGAL were reduced. Since urine NGAL levels appear to be dependent on plasma levels, the renal handling of circulating NGAL was examined using recombinant human NGAL. After intravenous recombinant human NGAL administration to mice, human NGAL in mouse urine was detected by ELISA during proximal tubular dysfunction, but not in pre-renal azotemia. Thus, during AKI, IL-6 mediates hepatic NGAL production, hepatocytes are the primary source of plasma and urine NGAL, and plasma NGAL appears in the urine during proximal tubule dysfunction. Hence, our data change the paradigm by which NGAL should be interpreted as a biomarker of AKI.
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