ArticleAmerican journal of physiology. Renal physiology2018
Arginine reprogramming in ADPKD results in arginine-dependent cystogenesis.
Article in American journal of physiology. Renal physiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Plasma metabolites and lipids associate with kidney function and kidney volume in hypertensive ADPKD patients early in the disease course.BMC nephrology · 2019Trial
- 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
- Plasma Amino Acid Signatures Associated with Disease Progression and Hypertension in Autosomal Dominant Polycystic Kidney Disease: A Targeted Metabolomics and Machine Learning Approach.Journal of clinical medicine · 2026Article
- 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
- Wheat-Based Protein Slows Disease Progression in Pkd1 Knockout Mice.Function (Oxford, England) · 2025Article
- Metabolic Reprogramming in Autosomal Dominant Polycystic Kidney Disease: Role in Cystogenesis and Novel Therapeutic Approaches.Biomedicines · 2025Review
- Metabolic reprogramming in polycystic kidney disease and other renal ciliopathies.EMBO molecular medicine · 2025Review
- Autosomal Dominant Polycystic Kidney Disease-Related Multifocal Renal Cell Carcinoma: A Narrative Iconographic Review.International journal of molecular sciences · 2025Review
- Targeted Analysis of Serum and Urinary Metabolites for Early Chronic Kidney Disease.International journal of molecular sciences · 2025Article
- Electrolyte and metabolite composition of cystic fluid from a rat model of ARPKD.Communications biology · 2025Article
- Amino acid metabolism in kidney health and disease.Nature reviews. Nephrology · 2024Review
- A brief harvesting-freezing delay significantly alters the kidney metabolome and leads to false positive and negative results.American journal of physiology. Renal physiology · 2024Article
- The Influence of Non-Pharmacological and Pharmacological Interventions on the Course of Autosomal Dominant Polycystic Kidney Disease.Nutrients · 2024Review
- Reprogramming of Energy Metabolism in HumanInternational journal of molecular sciences · 2024Article
- The Role of the L-Arginine-Nitric Oxide Molecular Pathway in Autosomal Dominant Polycystic Kidney Disease.Journal of personalized medicine · 2024Article
- Disturbances in Nitric Oxide Cycle and Related Molecular Pathways in Clear Cell Renal Cell Carcinoma.Cancers · 2023Review
- Short salsalate administration affects cell proliferation, metabolism, and inflammation in polycystic kidney disease.iScience · 2023Article
- Dehydration Accelerates Cytogenesis and Cyst Growth in Pkd1Inflammation · 2023Article
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Research into metabolic reprogramming in cancer has become commonplace, yet this area of research has only recently come of age in nephrology. In light of the parallels between cancer and autosomal dominant polycystic kidney disease (ADPKD), the latter is currently being studied as a metabolic disease. In clear cell renal cell carcinoma (RCC), which is now considered a metabolic disease, we and others have shown derangements in the enzyme arginosuccinate synthase 1 (ASS1), resulting in RCC cells becoming auxotrophic for arginine and leading to a new therapeutic paradigm involving reducing extracellular arginine. Based on our earlier finding that glutamine pathways are reprogrammed in ARPKD, and given the connection between arginine and glutamine synthetic pathways via citrulline, we investigated the possibility of arginine reprogramming in ADPKD. We now show that, in a remarkable parallel to RCC, ASS1 expression is reduced in murine and human ADPKD, and arginine depletion results in a dose-dependent compensatory increase in ASS1 levels as well as decreased cystogenesis in vitro and ex vivo with minimal toxicity to normal cells. Nontargeted metabolomics analysis of mouse kidney cell lines grown in arginine-deficient versus arginine-replete media suggests arginine-dependent alterations in the glutamine and proline pathways. Thus, depletion of this conditionally essential amino acid by dietary or pharmacological means, such as with arginine-degrading enzymes, may be a novel treatment for this disease.
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