ArticlePloS one2014
Rapid renal alpha-1 antitrypsin gene induction in experimental and clinical acute kidney injury.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Biomarkers of systemic lupus erythematosus identified using mass spectrometry-based proteomics: a systematic review.Journal of cellular and molecular medicine · 2017Pooled it
- The relationship of neutrophil elastase and proteinase 3 with risk factors, and chronic complications in type 2 diabetes: A Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) sub-study.Diabetes & vascular disease researchTrial
- Dysregulated Protease Homeostasis Defines Primary FSGS.Kidney360 · 2026Article
- Alpha-1 Antitrypsin Protects Against Cisplatin-Induced Acute Kidney Injury by Restoring Redox and Mitochondrial Homeostasis.Biomolecules · 2026Article
- Diagnosis and Emerging Biomarkers of Cystic Fibrosis-Related Kidney Disease (CFKD).Journal of clinical medicine · 2025Review
- Administration of Purified Alpha-1 Antitrypsin in Salt-Loaded Hypertensive 129Sv Mice Attenuates the Expression of Inflammatory Associated Proteins in the Kidney.Biomolecules · 2025Article
- A neutrophil elastase inhibitor, sivelestat, attenuates sepsis-induced acute kidney injury by inhibiting oxidative stress.Heliyon · 2024Article
- Urinary peptide analysis to predict the response to blood pressure medication.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Article
- Recent Advances of Proteomics in Management of Acute Kidney Injury.Diagnostics (Basel, Switzerland) · 2023Review
- Urinary proteome analysis of acute kidney injury in post-cardiac surgery patients using enrichment materials with high-resolution mass spectrometry.Frontiers in bioengineering and biotechnology · 2022Article
- Article
- The Acute Phase Response Is a Prominent Renal Proteome Change in Sepsis in Mice.International journal of molecular sciences · 2019Article
- Discovery of SERPINA3 as a candidate urinary biomarker of lupus nephritis activity.Rheumatology (Oxford, England) · 2019Article
- Chronic kidney disease: a review of proteomic and metabolomic approaches to membranous glomerulonephritis, focal segmental glomerulosclerosis, and IgA nephropathy biomarkers.Proteome science · 2019Review
- A combination of SOFA score and biomarkers gives a better prediction of septic AKI and in-hospital mortality in critically ill surgical patients: a pilot study.World journal of emergency surgery : WJES · 2018Article
- Targeting Phospholipase D4 Attenuates Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2017Article
- Comparative differential proteomic analysis of minimal change disease and focal segmental glomerulosclerosis.BMC nephrology · 2017Article
- Article
- Evaluation of Alpha-1 Antitrypsin Levels andFrontiers in immunology · 2017Article
- The neutrophil elastase inhibitor, sivelestat, attenuates sepsis-related kidney injury in rats.International journal of molecular medicine · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Alpha-1-antitrypsin (AAT) is a hepatic stress protein with protease inhibitor activity. Recent evidence indicates that ischemic or toxic injury can evoke selective changes within kidney that resemble a hepatic phenotype. Hence, we tested the following: i) Does acute kidney injury (AKI) up-regulate the normally renal silent AAT gene? ii) Does rapid urinary AAT excretion result? And iii) Can AAT's anti-protease/anti-neutrophil elastase (NE) activity protect injured proximal tubule cells? CD-1 mice were subjected to ischemic or nephrotoxic (glycerol, maleate, cisplatin) AKI. Renal functional and biochemical assessments were made 4-72 hrs later. Rapidly following injury, 5-10 fold renal cortical and isolated proximal tubule AAT mRNA and protein increases occurred. These were paralleled by rapid (>100 fold) increases in urinary AAT excretion. AKI also induced marked increases in renal cortical/isolated proximal tubule NE mRNA. However, sharp NE protein levels declines resulted, which strikingly correlated (r, -0.94) with rising AAT protein levels (reflecting NE complexing by AAT/destruction). NE addition to HK-2 cells evoked ∼95% cell death. AAT completely blocked this NE toxicity, as well as Fe induced oxidant HK-2 cell attack. Translational relevance of experimental AAT gene induction was indicated by ∼100-1000 fold urinary AAT increases in 22 AKI patients (matching urine NGAL increases). We conclude: i) AKI rapidly up-regulates the renal cortical/proximal tubule AAT gene; ii) NE gene induction also results; iii) AAT can confer cytoprotection, potentially by blocking/reducing cytotoxic NE accumulation; and iv) marked increases in urinary AAT excretion in AKI patients implies clinical relevance of the AKI- AAT induction pathway.
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Registered trials
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