ArticleNature medicine2013
Defective glucose metabolism in polycystic kidney disease identifies a new therapeutic strategy.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07651397 (Open Labeled , Randomized, Controlled, Crossover Trial on the Effect of a Carbohydrate Restricted Plant Dominant Diet on MCP-1 Mediated Inflammatory Signaling in Autosomal Dominant Polycystic Kidney Disease), which is not on this map. Cited by 309 papers, 3 of them syntheses that pooled it.
What it found
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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.
Open Labeled , Randomized, Controlled, Crossover Trial on the Effect of a Carbohydrate Restricted Plant Dominant Diet on MCP-1 Mediated Inflammatory Signaling in Autosomal Dominant Polycystic Kidney Disease
Who cites it
309 citing papers in PubMed, 3 syntheses or guidelines pooled it, 486 citations in OpenAlex.
- Comparison of somatostatin analogues on glucose metabolism: A systematic review and network Meta-Analysis of randomized controlled trials.Endocrine · 2026Pooled it
- Impact of polycystic kidney disease on outcomes after renal transplantation: systematic review and meta-analysis.Renal failure · 2025Pooled it
- Therapeutic Potential of Ketogenic Interventions for Autosomal-Dominant Polycystic Kidney Disease: A Systematic Review.Nutrients · 2024Pooled it
- Feasibility and impact of ketogenic dietary interventions in polycystic kidney disease: KETO-ADPKD-a randomized controlled trial.Cell reports. Medicine · 2023Trial
- RESET-PKD: a pilot trial on short-term ketogenic interventions in autosomal dominant polycystic kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2023Trial
- Effects of Hydrochlorothiazide and Metformin on Aquaresis and Nephroprotection by a Vasopressin V2 Receptor Antagonist in ADPKD: A Randomized Crossover Trial.Clinical journal of the American Society of Nephrology : CJASN · 2022Trial
- Metformin Therapy in Autosomal Dominant Polycystic Kidney Disease: A Feasibility Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2022Trial
- Primary results of the randomized trial of metformin administration in polycystic kidney disease (TAME PKD).Kidney international · 2021Trial
- Baseline Characteristics and Patient-Reported Outcomes of ADPKD Patients in the Multicenter TAME-PKD Clinical Trial.Kidney360 · 2020Trial
- Urinary metabolites associate with the rate of kidney function decline in patients with autosomal dominant polycystic kidney disease.PloS one · 2020Trial
- Unmasking Early Hepatorenal Fibrosis in Polycystic Kidney Disease Using Noninvasive Precision Molecular MRI of Collagen.bioRxiv : the preprint server for biology · 2026Article
- Renal gluconeogenesis: a key metabolic hub in health and kidney disease.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026Review
- Modeling Complex Developmental Disease: The Case of Polycystic Kidney Disease.Journal of developmental biology · 2026Review
- Amino acid homeostasis in the kidney: Physiological roles and pathological dysregulation.Physiological reports · 2026Review
- Myofibroblast- specific autophagy drives cyst growth in autosomal dominant polycystic kidney disease.Cell communication and signaling : CCS · 2026Article
- Glis3 Is a Modifier of Cyst Progression in Autosomal Dominant Polycystic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2026Article
- Compartmentalized Nutrient and Hormone Sensing in β-Cells: the Role of Primary Cilia.Physiology (Bethesda, Md.) · 2026Review
- Review
- The Renal Micro-RNA Expression Profile of Pkd1RC/RC Mice Changes Longitudinally with the Progression of the Disease.Kidney360 · 2026Article
- Kidney Volume and Molecular Processes are Dynamic in ADPKD.Kidney international reports · 2026Article
249 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by bilateral renal cyst formation. Recent identification of signaling cascades deregulated in ADPKD has led to the initiation of several clinical trials, but an approved therapy is still lacking. Using a metabolomic approach, we identify a pathogenic pathway in this disease that can be safely targeted for therapy. We show that mutation of PKD1 results in enhanced glycolysis in cells in a mouse model of PKD and in kidneys from humans with ADPKD. Glucose deprivation resulted in lower proliferation and higher apoptotic rates in PKD1-mutant cells than in nondeprived cells. Notably, two distinct PKD mouse models treated with 2-deoxyglucose (2DG), to inhibit glycolysis, had lower kidney weight, volume, cystic index and proliferation rates as compared to nontreated mice. These metabolic alterations depend on the extracellular signal-related kinase (ERK) pathway acting in a dual manner by inhibiting the liver kinase B1 (LKB1)-AMP-activated protein kinase (AMPK) axis on the one hand while activating the mTOR complex 1 (mTORC1)-glycolytic cascade on the other. Enhanced metabolic rates further inhibit AMPK. Forced activation of AMPK acts in a negative feedback loop, restoring normal ERK activity. Taken together, these data indicate that defective glucose metabolism is intimately involved in the pathobiology of ADPKD. Our findings provide a strong rationale for a new therapeutic strategy using existing drugs, either individually or in combination.
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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.