ArticleJCI insight2022
Impaired fatty acid metabolism perpetuates lipotoxicity along the transition to chronic kidney injury.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 53 citations in OpenAlex.
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- Renal single-nucleus transcriptomic of a new model of cardiovascular-kidney-metabolic syndrome in aging swine.American journal of physiology. Renal physiology · 2026Article
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- The roles of free-fatty acid receptors in the pathophysiology of renal disorders.The Journal of pharmacology and experimental therapeutics · 2026Review
- Mapping Spatiotemporal Metabolic Perturbations in Alloxan-Induced Diabetic Rat Kidneys Using Spatial Metabolomics and Proteomic Integration.Metabolites · 2026Article
- Carnitine dysregulation in diabetic kidney disease: from pathogenic mechanism to precision biomarker.Journal of translational medicine · 2026Review
- Dapagliflozin induces renal lipidomic remodeling and systemic metabolic improvement.Biology direct · 2026Article
- Hyperlipidemia in membranous nephropathy.Clinical kidney journal · 2026Review
- Pyrimidinergic calcium signaling links tubular metabolism to fibrosis in kidney disease.Nature communications · 2026Article
- Myokine SIRPα exacerbates kidney disease in diabetes.JCI insight · 2026Article
- ACSM5 c.1273 C> A Polymorphism Promotes Malignant Progression of Lung Adenocarcinoma in Xuanwei Region.Applied biochemistry and biotechnology · 2026Article
- Integrating WGCNA and machine learning algorithm to identify ACSM5 as a prognostic biomarker and therapeutic target for predicting immunotherapy efficacy in non-small cell lung cancer.Translational cancer research · 2026Article
- Histological Features of Kidney Allograft Biopsies According to Metabolic Acidosis Status: A Biopsy-Based Single-Center Observational Study.Life (Basel, Switzerland) · 2026Article
- Role of metabolic reprogramming and lactylation in diabetic nephropathy: molecular mechanisms and therapeutic prospects - a narrative review.Frontiers in endocrinology · 2026Review
- Linear association between atherogenic index of plasma and diabetic kidney disease: evidence from a large clinical cohort and NHANES.Frontiers in nutrition · 2026Article
- Triglyceride-glucose index and its derivatives as emerging biomarkers of insulin resistance for prognostic evaluation of cardiovascular-kidney-metabolic syndrome: mechanisms and clinical applications.Frontiers in pharmacology · 2026Review
- Dietary methionine deprivation enhances renal resilience against ischemia-reperfusion injury in mice through modulation of glucose oxidation.Communications biology · 2025Article
- Biomimetic ferritin nanocages for synergistic co-delivery of metformin and rapamycin restore neurodevelopmental homeostasis in autism spectrum disorders.Journal of nanobiotechnology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Energy metabolism failure in proximal tubule cells (PTCs) is a hallmark of chronic kidney injury. We combined transcriptomic, metabolomic, and lipidomic approaches in experimental models and patient cohorts to investigate the molecular basis of the progression to chronic kidney allograft injury initiated by ischemia/reperfusion injury (IRI). The urinary metabolome of kidney transplant recipients with chronic allograft injury and who experienced severe IRI was substantially enriched with long chain fatty acids (FAs). We identified a renal FA-related gene signature with low levels of carnitine palmitoyltransferase 2 (Cpt2) and acyl-CoA synthetase medium chain family member 5 (Acsm5) and high levels of acyl-CoA synthetase long chain family member 4 and 5 (Acsl4 and Acsl5) associated with IRI, transition to chronic injury, and established chronic kidney disease in mouse models and kidney transplant recipients. The findings were consistent with the presence of Cpt2-Acsl4+Acsl5+Acsm5- PTCs failing to recover from IRI as identified by single-nucleus RNA-Seq. In vitro experiments indicated that ER stress contributed to CPT2 repression, which, in turn, promoted lipids' accumulation, drove profibrogenic epithelial phenotypic changes, and activated the unfolded protein response. ER stress through CPT2 inhibition and lipid accumulation engaged an auto-amplification loop leading to lipotoxicity and self-sustained cellular stress. Thus, IRI imprints a persistent FA metabolism disturbance in the proximal tubule, sustaining the progression to chronic kidney allograft injury.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.