ArticleJCI insight2023
The tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase 1 regulates polycystic kidney disease progression.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- The Role of Immune Cells as Modulators of Progression in Polycystic Kidney Disease: A Systematic Review.Kidney360 · 2026Pooled it
- T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Role of Gut Microbiota in Bridging Vitamin D Deficiency and Type 2 Diabetes Mellitus Pathogenesis.Microorganisms · 2026Review
- Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.Journal of the American Society of Nephrology : JASN · 2026Article
- Untangling amino acid metabolism in renal diseases: mechanisms, dysregulation, and critical gaps.Clinical kidney journal · 2026Review
- Microbiota-associated metabolic networks in gut-kidney communication and renal immune regulation: mechanisms and therapeutic potential.Frontiers in microbiology · 2026Review
- The exocyst in ciliogenesis.Renal failure · 2025Review
- Commemorating the National Institute of Diabetes and Digestive and Kidney Diseases' Advances in Kidney Health: 75 Years of Discovery and Impact.Clinical journal of the American Society of Nephrology : CJASN · 2025Article
- Wheat-Based Protein Slows Disease Progression in Pkd1 Knockout Mice.Function (Oxford, England) · 2025Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.Cellular & molecular biology letters · 2025Review
- Metabolic reprogramming in polycystic kidney disease and other renal ciliopathies.EMBO molecular medicine · 2025Review
- Electrolyte and metabolite composition of cystic fluid from a rat model of ARPKD.Communications biology · 2025Article
- Intestinal barrier function declines during polycystic kidney disease progression.American journal of physiology. Renal physiology · 2025Article
- Amino acid metabolism in kidney health and disease.Nature reviews. Nephrology · 2024Review
- Cilia-deficient renal tubule cells are primed for injury with mitochondrial defects and aberrant tryptophan metabolism.American journal of physiology. Renal physiology · 2024Article
- Indoleamine 2,3-dioxygenase 1-mediated iron metabolism in macrophages contributes to lipid deposition in nonalcoholic steatohepatitis.Journal of gastroenterology · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD), the most common monogenic nephropathy, is characterized by phenotypic variability that exceeds genic effects. Dysregulated metabolism and immune cell function are key disease modifiers. The tryptophan metabolites, kynurenines, produced through indoleamine 2,3-dioxygenase 1 (IDO1), are known immunomodulators. Here, we study the role of tryptophan metabolism in PKD using an orthologous disease model (C57BL/6J Pkd1RC/RC). We found elevated kynurenine and IDO1 levels in Pkd1RC/RC kidneys versus wild type. Further, IDO1 levels were increased in ADPKD cell lines. Genetic Ido1 loss in Pkd1RC/RC animals resulted in reduced PKD severity, as measured by cystic index and percentage kidney weight normalized to body weight. Consistent with an immunomodulatory role of kynurenines, Pkd1RC/RC;Ido1-/- mice presented with significant changes in the cystic immune microenvironment (CME) versus controls. Kidney macrophage numbers decreased and CD8+ T cell numbers increased, both known PKD modulators. Also, pharmacological IDO1 inhibition in Pkd1RC/RC mice and kidney-specific Pkd2-knockout mice with rapidly progressive PKD resulted in less severe PKD versus controls, with changes in the CME similar to those in the genetic model. Our data suggest that tryptophan metabolism is dysregulated in ADPKD and that its inhibition results in changes to the CME and slows disease progression, making IDO1 a therapeutic target for ADPKD.
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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.