ArticleNature medicine2014
Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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
98 citing papers in PubMed, 170 citations in OpenAlex.
- Effect of atorvastatin on dyslipidemia and carotid intima-media thickness in children with refractory nephrotic syndrome: a randomized controlled trial.Pediatric nephrology (Berlin, Germany) · 2018 · on this mapTrial
- The High-Sensitivity C-Reactive Protein-Albumin-Lymphocyte Index Is a Prognostic Marker for All-Cause and Cardiovascular Mortality in Patients With ST-Elevation Myocardial Infarction.Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions · 2026Article
- ANGPTL4 Exacerbates Renal Injury in Diabetic Kidney Disease by Impairing Podocyte Lipophagy via Compromised Lysosomal Degradative Function.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cardiovascular disease and risk management in patients with nephrotic syndrome.Kidney research and clinical practice · 2026Article
- Depletion of renal cortical collecting duct-secreted PCSK9 in early proteinuria prevents sustained nephrotic syndrome-related hypercholesterolemia.American journal of physiology. Renal physiology · 2026Article
- Very low-density lipoprotein and the human health.World journal of experimental medicine · 2026Review
- Macrophage migration inhibitory factor and angiopoietin-like protein 4 as markers for steroid response in children with idiopathic nephrotic syndrome.Pediatric nephrology (Berlin, Germany) · 2026Article
- Serum Factors in Primary Podocytopathies.Antibodies (Basel, Switzerland) · 2025Review
- The Life of a Kidney Podocyte.Acta physiologica (Oxford, England) · 2025Review
- Metabolic reprogramming by endothelial ANGPTL4 depletion protects against diabetic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- The Spectrum of Minimal Change Disease/Focal Segmental Glomerulosclerosis: From Pathogenesis to Proteomic Biomarker Research.International journal of molecular sciences · 2025Review
- ANGPTL4-the Link Binding Lipid Metabolism and Inflammation.Current medicinal chemistry · 2025Review
- Editorial: Diabetic kidney disease: routes to drug development, pharmacology and underlying molecular mechanisms, volume II.Frontiers in pharmacology · 2025Article
- Advancing the clinical assessment of glomerular podocyte pathology in kidney biopsies via super-resolution microscopy and angiopoietin-like 4 staining.Theranostics · 2025Article
- Renal Angptl4 is a key fibrogenic molecule in progressive diabetic kidney disease.Science advances · 2024Article
- Angiopoietin-like 4 is a potential biomarker for diabetic kidney disease in type 2 diabetes patients.Journal of diabetes investigation · 2024Article
- Lactylated Apolipoprotein C-II Induces Immunotherapy Resistance by Promoting Extracellular Lipolysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Postpartum Renal Cortical Necrosis: A Case Series.Kidney medicine · 2024Article
- Dyslipidemia in children with chronic kidney disease-findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study.Pediatric nephrology (Berlin, Germany) · 2024Article
- Sodium-Glucose Cotransporter Inhibitors: Cellular Mechanisms Involved in the Lipid Metabolism and the Treatment of Chronic Kidney Disease Associated with Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2024Review
38 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
6 authors at 4 institutions in 4 countries.
Funding
Abstract
The molecular link between proteinuria and hyperlipidemia in nephrotic syndrome is not known. We show in the present study that plasma angiopoietin-like 4 (Angptl4) links proteinuria with hypertriglyceridemia through two negative feedback loops. In previous studies in a rat model that mimics human minimal change disease, we observed localized secretion by podocytes of hyposialylated Angptl4, a pro-proteinuric form of the protein. But in this study we noted high serum levels of Angptl4 (presumably normosialylated based on a neutral isoelectric point) in other glomerular diseases as well. Circulating Angptl4 was secreted by extrarenal organs in response to an elevated plasma ratio of free fatty acids (FFAs) to albumin when proteinuria reached nephrotic range. In a systemic feedback loop, these circulating pools of Angptl4 reduced proteinuria by interacting with glomerular endothelial αvβ5 integrin. Blocking the Angptl4-β5 integrin interaction or global knockout of Angptl4 or β5 integrin delayed recovery from peak proteinuria in animal models. But at the same time, in a local feedback loop, the elevated extrarenal pools of Angptl4 reduced tissue FFA uptake in skeletal muscle, heart and adipose tissue, subsequently resulting in hypertriglyceridemia, by inhibiting lipoprotein lipase (LPL)-mediated hydrolysis of plasma triglycerides to FFAs. Injecting recombinant human ANGPTL4 modified at a key LPL interacting site into nephrotic Buffalo Mna and Zucker Diabetic Fatty rats reduced proteinuria through the systemic loop but, by bypassing the local loop, without increasing plasma triglyceride levels. These data show that increases in circulating Angptl4 in response to nephrotic-range proteinuria reduces the degree of this pathology, but at the cost of inducing hypertriglyceridemia, while also suggesting a possible therapy to treat these linked pathologies.
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.