Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

A guide to uraemic toxicity

Nature Reviews Nephrology volume 22, pages 50–68 (2026)Cite this article

Subjects

Abstract

When kidney function is compromised, myriad metabolites and peptides — uraemic retention molecules (URMs) — accumulate in the body and compromise homeostasis. Over 150 molecules have been classified as URMs but omics approaches are revealing many more. When URMs exert pathophysiological effects and/or are associated with relevant adverse patient outcomes, they are called uraemic toxins. The origins of uraemic toxins and their contributions to post-translational modification of proteins are important current areas of research. Although most research has thus far focused on uraemic toxins, new studies have also identified URMs with the potential to counteract harmful biological changes that might thus confer a beneficial effect. To tackle the growing burden of chronic kidney disease, preventive therapeutic measures must target the disease early in its course and a balanced view of uraemic retention is needed to understand the role of URMs in kidney disease progression. Knowledge of the origin of the solutes, their kinetics, context-dependent biological profile and the involvement of transporter-mediated interorgan communication by small molecules — termed ‘remote sensing and signalling’ — is indispensable to facilitate the development of interventions that can promote or restore homeostasis in people with kidney dysfunction.

Key points

  • Uraemic retention molecules, which accumulate as kidney function declines, are key mediators in the pathophysiology of chronic kidney disease.

  • Uraemic retention molecules can be deleterious for the whole organism (termed uraemic toxins) but can also have beneficial effects.

  • Identification of uraemic toxin receptors and downstream affected signalling pathways is key to understanding their pathological effects and developing targeted therapeutic strategies.

  • Chronic kidney disease is associated with alterations in protein post-translational modifications, which can transform physiological molecules into mediators of pathology.

  • Various promising therapeutic approaches to reducing uraemic toxicity, including drug therapy, nutritional approaches, new dialysis membrane materials, as well as bioartificial and wearable artificial kidneys, are currently being investigated.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Pathophysiological changes with a central role in kidney dysfunction and uraemic toxin retention.
Fig. 2: Classification of uraemic retention molecules.
Fig. 3: Remote sensing and signalling, and the role of metabolism and transport of indoxyl sulfate.
Fig. 4: Therapeutic strategies to reduce uraemic toxin production, accumulation and toxicity.

Similar content being viewed by others

References

  1. Zoccali, C. et al. The systemic nature of CKD. Nat. Rev. Nephrol. 13, 344–358 (2017).

    Article  PubMed  Google Scholar 

  2. Afkarian, M. et al. Kidney disease and increased mortality risk in type 2 diabetes. J. Am. Soc. Nephrol. 24, 302–308 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Wan, E. Y. F. et al. Burden of CKD and cardiovascular disease on life expectancy and health service utilization: a cohort study of Hong Kong Chinese hypertensive patients. J. Am. Soc. Nephrol. 30, 1991–1999 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kalantar-Zadeh, K. et al. Patient-centred approaches for the management of unpleasant symptoms in kidney disease. Nat. Rev. Nephrol. 18, 185–198 (2022).

    Article  PubMed  Google Scholar 

  5. Foley, R. N., Parfrey, P. S. & Sarnak, M. J. Clinical epidemiology of cardiovascular disease in chronic renal disease. Am. J. Kidney Dis. 32, S112–S119 (1998).

    Article  CAS  PubMed  Google Scholar 

  6. Matsushita, K. et al. Epidemiology and risk of cardiovascular disease in populations with chronic kidney disease. Nat. Rev. Nephrol. 18, 696–707 (2022).

    Article  PubMed  Google Scholar 

  7. Modi, Z. J. et al. Risk of cardiovascular disease and mortality in young adults with end-stage renal disease: an analysis of the US renal data system. JAMA Cardiol. 4, 353–362 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  8. NCD_Alliance. Home / WHY NCDs / NCDs / Chronic Kidney Disease. ncdalliance.org https://ncdalliance.org/why-ncds/ncds/chronic-kidney-disease (2017).

  9. Rosner, M. H. et al. Classification of uremic toxins and their role in kidney failure. Clin. J. Am. Soc. Nephrol. 16, 1918–1928 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Jaksch On uræmia. Chic. Med. J. 18, 396–397 (1861).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Balestri, P. L., Biagini, M., Rindi, P. & Giovannetti, S. Uremic toxins. Arch. Intern. Med. 126, 843–845 (1970).

    Article  CAS  PubMed  Google Scholar 

  12. Desi, I., Feher, E., Szold, A., Weisz, P. & Kadas, T. [Determination of toxicity of uremic blood treated with ion exchange resins]. Z. Gesamte Inn. Med. 12, 1127–1130 (1957).

    CAS  PubMed  Google Scholar 

  13. Babb, A. L., Ahmad, S., Bergström, J. & Scribner, B. H. The middle molecule hypothesis in perspective. Am. J. Kidney Dis. 1, 46–50 (1981).

    Article  CAS  PubMed  Google Scholar 

  14. Thomas, M., Moriyama, K. & Ledebo, I. AN69: evolution of the world’s first high permeability membrane. Contrib. Nephrol. 173, 119–129 (2011).

    Article  CAS  PubMed  Google Scholar 

  15. Gejyo, F. et al. A new form of amyloid protein associated with chronic hemodialysis was identified as β2-microglobulin. Biochem. Biophys. Res. Commun. 129, 701–706 (1985).

    Article  CAS  PubMed  Google Scholar 

  16. Kasanen, A. Serum indican and endogenous indican clearance in renal insufficiency. Ann. Med. Intern. Fenn. Suppl. 46, 1–71 (1957).

    CAS  PubMed  Google Scholar 

  17. Niwa, T. & Ise, M. Indoxyl sulfate, a circulating uremic toxin, stimulates the progression of glomerular sclerosis. J. Lab. Clin. Med. 124, 96–104 (1994).

    CAS  PubMed  Google Scholar 

  18. Vanholder, R., Glorieux, G., De Smet, R. & Lameire, N. New insights in uremic toxins. Kidney Int. Suppl. 63, S6–S10.

  19. Vanholder, R. et al. Review on uremic toxins: classification, concentration, and interindividual variability. Kidney Int. 63, 1934–1943 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Duranton, F. et al. Normal and pathologic concentrations of uremic toxins. J. Am. Soc. Nephrol. 23, 1258–1270 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hocher, B. & Adamski, J. Metabolomics for clinical use and research in chronic kidney disease. Nat. Rev. Nephrol. 13, 269–284 (2017).

    Article  CAS  PubMed  Google Scholar 

  22. Vanholder, R. et al. Metabolomics to identify unclassified uremic toxins: a comprehensive literature review. Kidney Med. 7, 100955 (2025).

    Article  PubMed  Google Scholar 

  23. Luo, S. et al. Serum metabolomic alterations associated with proteinuria in CKD. Clin. J. Am. Soc. Nephrol. 14, 342–353 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Titan, S. M. et al. Metabolomics biomarkers and the risk of overall mortality and ESRD in CKD: results from the Progredir cohort. PLoS ONE 14, e0213764 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wen, D. et al. Metabolite profiling of CKD progression in the chronic renal insufficiency cohort study. JCI insight 7, e161696 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Lee, A. M. et al. Circulating metabolomic associations with neurocognitive outcomes in pediatric CKD. Clin. J. Am. Soc. Nephrol. 19, 13–25 (2024).

    Article  CAS  PubMed  Google Scholar 

  28. Kikuchi, K. et al. Gut microbiome-derived phenyl sulfate contributes to albuminuria in diabetic kidney disease. Nat. Commun. 10, 1835 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gajjala, P. R., Fliser, D., Speer, T., Jankowski, V. & Jankowski, J. Emerging role of post-translational modifications in chronic kidney disease and cardiovascular disease. Nephrol. Dial. Transplant. 30, 1814–1824 (2015).

    Article  CAS  PubMed  Google Scholar 

  30. Noels, H. et al. Post-translational modifications in kidney diseases and associated cardiovascular risk. Nat. Rev. Nephrol. 20, 495–512 (2024).

    Article  CAS  PubMed  Google Scholar 

  31. Meijers, B., Glorieux, G., Poesen, R. & Bakker, S. J. Nonextracorporeal methods for decreasing uremic solute concentration: a future way to go? Semin. Nephrol. 34, 228–243 (2014).

    Article  CAS  PubMed  Google Scholar 

  32. Mishima, E. et al. Evaluation of the impact of gut microbiota on uremic solute accumulation by a CE-TOFMS-based metabolomics approach. Kidney Int. 92, 634–645 (2017).

    Article  CAS  PubMed  Google Scholar 

  33. Evenepoel, P, Meijers, B. K., Bammens, B. R. & Verbeke, K. Uremic toxins originating from colonic microbial metabolism. Kidney Int. 76 (Supp. 114), S12–S19 (2009).

    Article  Google Scholar 

  34. Wikoff, W. R., Nagle, M. A., Kouznetsova, V. L., Tsigelny, I. F. & Nigam, S. K. Untargeted metabolomics identifies enterobiome metabolites and putative uremic toxins as substrates of organic anion transporter 1 (Oat1). J. Proteome Res. 10, 2842–2851 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Vanholder, R., Nigam, S. K., Burtey, S. & Glorieux, G. What if not all metabolites from the uremic toxin generating pathways are toxic? A hypothesis. Toxins 14, 221 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Ahn, S. Y. & Nigam, S. K. Toward a systems level understanding of organic anion and other multispecific drug transporters: a remote sensing and signaling hypothesis. Mol. Pharmacol. 76, 481–490 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Nigam, S. K. & Bush, K. T. Uraemic syndrome of chronic kidney disease: altered remote sensing and signalling. Nat. Rev. Nephrol. 15, 301–316 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Sun, C. Y. et al. Protein-bound uremic toxins induce tissue remodeling by targeting the EGF receptor. J. Am. Soc. Nephrol. 26, 281–290 (2015).

    Article  PubMed  Google Scholar 

  39. Shepard, B. D. & Pluznick, J. L. How does your kidney smell? Emerging roles for olfactory receptors in renal function. Pediatr. Nephrol. 31, 715–723 (2016).

    Article  PubMed  Google Scholar 

  40. Wu, W. et al. Shared ligands between organic anion transporters (OAT1 and OAT6) and odorant receptors. Drug Metab. Dispos. 43, 1855–1863 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mihaila, S. M. et al. Drugs commonly applied to kidney patients may compromise renal tubular uremic toxins excretion. Toxins 12, 391 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mutsaers, H. A. et al. Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS ONE 6, e18438 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nigam, S. K. What do drug transporters really do? Nat. Rev. Drug. Discov. 14, 29–44 (2015).

    Article  CAS  PubMed  Google Scholar 

  44. Kimura, N., Masuda, S., Katsura, T. & Inui, K. Transport of guanidine compounds by human organic cation transporters, hOCT1 and hOCT2. Biochem. Pharmacol. 77, 1429–1436 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Kuo, K. L., Zhu, H., McNamara, P. J. & Leggas, M. Localization and functional characterization of the rat Oatp4c1 transporter in an in vitro cell system and rat tissues. PLoS ONE 7, e39641 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Schophuizen, C. M. et al. Cationic uremic toxins affect human renal proximal tubule cell functioning through interaction with the organic cation transporter. Pflugers Arch. 465, 1701–1714 (2013).

    Article  CAS  PubMed  Google Scholar 

  47. Taghikhani, E., Maas, R., Fromm, M. F. & König, J. The renal transport protein OATP4C1 mediates uptake of the uremic toxin asymmetric dimethylarginine (ADMA) and efflux of cardioprotective L-homoarginine. PLoS ONE 14, e0213747 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pengrattanachot, N. et al. Atorvastatin attenuates obese-induced kidney injury and impaired renal organic anion transporter 3 function through inhibition of oxidative stress and inflammation. Biochim. Biophys. Acta Mol. Basis Dis. 1866, 165741 (2020).

    Article  CAS  PubMed  Google Scholar 

  49. Zhang, J., Wang, H., Fan, Y., Yu, Z. & You, G. Regulation of organic anion transporters: Role in physiology, pathophysiology, and drug elimination. Pharmacol. Ther. 217, 107647 (2021).

    Article  CAS  PubMed  Google Scholar 

  50. Santana Machado, T. et al. Indoxyl sulfate upregulates liver P-glycoprotein expression and activity through aryl hydrocarbon receptor signaling. J. Am. Soc. Nephrol. 29, 906–918 (2018).

    Article  PubMed  Google Scholar 

  51. Bhatnagar, V. et al. Analysis of ABCG2 and other urate transporters in uric acid homeostasis in chronic kidney disease: potential role of remote sensing and signaling. Clin. Kidney J. 9, 444–453 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Ermakov, V. S., Granados, J. C. & Nigam, S. K. Remote effects of kidney drug transporter OAT1 on gut microbiome composition and urate homeostasis. JCI insight 8, e172341 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  53. Morimoto, K. et al. Intestinal secretion of indoxyl sulfate as a possible compensatory excretion pathway in chronic kidney disease. Biopharm. Drug Dispos. 39, 328–334 (2018).

    Article  CAS  PubMed  Google Scholar 

  54. Jansen, J. et al. Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion. Proc. Natl Acad. Sci. USA 116, 16105–16110 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Makhloufi, C. et al. Female AhR knockout mice develop a minor renal insufficiency in an adenine-diet model of chronic kidney disease. Int. J. Mol. Sci. 21, 2483 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Gou, X., Ran, F., Yang, J., Ma, Y. & Wu, X. Construction and evaluation of a novel organic anion transporter 1/3 CRISPR/Cas9 double-knockout rat model. Pharmaceutics 14, 2307 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Lauriola, M. et al. Dietary protein intake and the tubular handling of indoxyl sulfate. Nephrol. Dial. Transplant. 40, 739–750 (2025).

    Article  CAS  PubMed  Google Scholar 

  58. Castillo-Rodríguez, E. et al. Inflammatory cytokines as uremic toxins: “Ni Son Todos Los Que Estan, Ni Estan Todos Los Que Son”. Toxins 9, 114 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  59. Gryp, T., Vanholder, R., Vaneechoutte, M. & Glorieux, G. p-Cresyl sulfate. Toxins 9, 52 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kuczera, P., Adamczak, M. & Wiecek, A. Fibroblast growth factor-23-a potential uremic toxin. Toxins 8, 369 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  61. Leong, S. C. & Sirich, T. L. Indoxyl sulfate-review of toxicity and therapeutic strategies. Toxins 8, 358 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Vanholder, R., Gryp, T. & Glorieux, G. Urea and chronic kidney disease: the comeback of the century? (in uraemia research). Nephrol. Dial. Transplant. 33, 4–12 (2018).

    Article  CAS  PubMed  Google Scholar 

  63. Vanholder, R., Pletinck, A., Schepers, E. & Glorieux, G. Biochemical and clinical impact of organic uremic retention solutes: a comprehensive update. Toxins 10, 33 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  64. Matsuki, H. et al. Chronic kidney disease causes blood-brain barrier breakdown via urea-activated matrix metalloproteinase-2 and insolubility of tau protein. Aging 15, 10972–10995 (2023).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Huang, B. Y. et al. High urea induces anxiety disorders associated with chronic kidney disease by promoting abnormal proliferation of OPC in amygdala. Eur. J. Pharmacol. 957, 175905 (2023).

    Article  CAS  PubMed  Google Scholar 

  66. Levassort, H. et al. Urea level and depression in patients with chronic kidney disease. Toxins 16, 326 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Xie, Y. et al. Higher blood urea nitrogen is associated with increased risk of incident diabetes mellitus. Kidney Int. 93, 741–752 (2018).

    Article  CAS  PubMed  Google Scholar 

  68. Laville, S. M. et al. Urea levels and cardiovascular disease in patients with chronic kidney disease. Nephrol. Dialysis Transplant. 38, 184–192 (2023).

    Article  CAS  Google Scholar 

  69. Kuma, A. et al. Inhibition of urea transporter ameliorates uremic cardiomyopathy in chronic kidney disease. FASEB J. 34, 8296–8309 (2020).

    Article  CAS  PubMed  Google Scholar 

  70. Jaisson, S., Pietrement, C. & Gillery, P. Carbamylation-derived products: bioactive compounds and potential biomarkers in chronic renal failure and atherosclerosis. Clin. Chem. 57, 1499–1505 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Wu, S. J. et al. Serum uric acid levels and health outcomes in CKD: a prospective cohort study. Nephrol. Dial. Transplant. 39, 510–519 (2024).

    Article  CAS  PubMed  Google Scholar 

  72. Badve, S. V. et al. Effects of allopurinol on the progression of chronic kidney disease. N. Engl. J. Med. 382, 2504–2513 (2020).

    Article  CAS  PubMed  Google Scholar 

  73. Doria, A. et al. Serum urate lowering with allopurinol and kidney function in type 1 diabetes. N. Engl. J. Med. 382, 2493–2503 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Heerspink, H. J. L. et al. Combination treatment with verinurad and allopurinol in CKD: a randomized placebo and active controlled trial. J. Am. Soc. Nephrol. 35, 594–606 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Triches, C. B., Quinto, M., Mayer, S., Batista, M. & Zanella, M. T. Relation of asymmetrical dimethylarginine levels with renal outcomes in hypertensive patients with and without type 2 diabetes mellitus. J. Diabetes Complications 32, 316–320 (2018).

    Article  PubMed  Google Scholar 

  76. Kobayashi, S. et al. Asymmetric dimethylarginine (ADMA) as a novel risk factor for progression of coronary artery calcification in patients with chronic kidney disease. J. Clin. Med. 14, 1051 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Emrich, I. E. et al. Symmetric dimethylarginine (SDMA) outperforms asymmetric dimethylarginine (ADMA) and other methylarginines as predictor of renal and cardiovascular outcome in non-dialysis chronic kidney disease. Clin. Res. Cardiol. 107, 201–213 (2018).

    Article  CAS  PubMed  Google Scholar 

  78. Eyileten, C. et al. High concentration of symmetric dimethylarginine is associated with low platelet reactivity and increased bleeding risk in patients with acute coronary syndrome. Thromb. Res. 213, 195–202 (2022).

    Article  CAS  PubMed  Google Scholar 

  79. Hannemann, J. et al. Symmetric dimethylarginine predicts previously undetected atrial fibrillation in patients with ischemic stroke. J. Am. Heart Assoc. 13, e034994 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Koppe, L. et al. The protein-bound uremic toxin p-cresyl-sulfate promotes intracellular ROS production and lipid peroxidation in 3T3-L1 adipose cells. Biochimie 189, 137–143 (2021).

    Article  CAS  PubMed  Google Scholar 

  81. Peng, Y. S., Syu, J. P., Wang, S. D., Pan, P. C. & Kung, H. N. BSA-bounded p-cresyl sulfate potentiates the malignancy of bladder carcinoma by triggering cell migration and EMT through the ROS/Src/FAK signaling pathway. Cell Biol. Toxicol. 36, 287–300 (2020).

    Article  CAS  PubMed  Google Scholar 

  82. Stafim da Cunha, R. et al. Uremic toxins activate CREB/ATF1 in endothelial cells related to chronic kidney disease. Biochem. Pharmacol. 198, 114984 (2022).

    Article  CAS  PubMed  Google Scholar 

  83. Chen, C. et al. Damage of uremic myocardium by p-cresyl sulfate and the ameliorative effect of Klotho by regulating SIRT6 ubiquitination. Toxicol. Lett. 367, 19–31 (2022).

    Article  CAS  PubMed  Google Scholar 

  84. Rodrigues, S. D. et al. Uremic toxins promote accumulation of oxidized protein and increased sensitivity to hydrogen peroxide in endothelial cells by impairing the autophagic flux. Biochem. Biophys. Res. Commun. 523, 123–129 (2020).

    Article  CAS  PubMed  Google Scholar 

  85. Opdebeeck, B. et al. Indoxyl sulfate and p-cresyl sulfate promote vascular calcification and associate with glucose intolerance. J. Am. Soc. Nephrol. 30, 751–766 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Shiba, T. et al. p-Cresyl sulfate decreases peripheral B cells in mice with adenine-induced renal dysfunction. Toxicol. Appl. Pharmacol. 342, 50–59 (2018).

    Article  CAS  PubMed  Google Scholar 

  87. Glorieux, G. et al. Free p-cresyl sulfate shows the highest association with cardiovascular outcome in chronic kidney disease. Nephrol. Dial. Transplant. 36, 998–1005 (2021).

    Article  CAS  PubMed  Google Scholar 

  88. Verbeke, F., Vanholder, R., Van Biesen, W. & Glorieux, G. Contribution of hypoalbuminemia and anemia to the prognostic value of plasma p-cresyl sulfate and p-cresyl glucuronide for cardiovascular outcome in chronic kidney disease. J. Pers. Med. 12, 1239 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Yang, K. et al. Indoxyl sulfate induces platelet hyperactivity and contributes to chronic kidney disease-associated thrombosis in mice. Blood 129, 2667–2679 (2017).

    Article  CAS  PubMed  Google Scholar 

  90. Hamano, H. et al. The uremic toxin indoxyl sulfate interferes with iron metabolism by regulating hepcidin in chronic kidney disease. Nephrol. Dial. Transplant. 33, 586–597 (2018).

    Article  CAS  PubMed  Google Scholar 

  91. Ribeiro, A. et al. Uremic toxin indoxyl sulfate promotes macrophage-associated low-grade inflammation and epithelial cell senescence. Int. J. Mol. Sci. 24, 8031 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Rodrigues, G. G. C. et al. Indoxyl sulfate contributes to uremic sarcopenia by inducing apoptosis in myoblasts. Arch. Med. Res. 51, 21–29 (2020).

    Article  CAS  PubMed  Google Scholar 

  93. Łukawski, K., Raszewski, G. & Czuczwar, S. J. Effects of the uremic toxin indoxyl sulfate on seizure activity, learning and brain oxidative stress parameters in mice. Neurosci. Lett. 820, 137594 (2024).

    Article  PubMed  Google Scholar 

  94. Bobot, M. et al. Uremic toxic blood-brain barrier disruption mediated by AhR activation leads to cognitive impairment during experimental renal dysfunction. J. Am. Soc. Nephrol. 31, 1509–1521 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Capasso, G. et al. Drivers and mechanisms of cognitive decline in chronic kidney disease. Nat. Rev. Nephrol. 21, 536–552 (2025).

    Article  PubMed  Google Scholar 

  96. Ichisaka, Y. et al. The role of indoxyl sulfate in exacerbating colorectal cancer during chronic kidney disease progression: insights into the Akt/β-catenin/c-Myc and AhR/c-Myc pathways in HCT-116 colorectal cancer cells. Toxins 17, 17 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Saito, S., Koya, Y., Kajiyama, H., Yamashita, M. & Nawa, A. Indoxyl sulfate promotes metastatic characteristics of ovarian cancer cells via aryl hydrocarbon receptor-mediated downregulation of the Mas receptor. Lab. Invest. 103, 100025 (2023).

    Article  CAS  PubMed  Google Scholar 

  98. Lou, F. et al. Dysbiotic oral microbiota-derived kynurenine, induced by chronic restraint stress, promotes head and neck squamous cell carcinoma by enhancing CD8+ T cell exhaustion. Gut 74, 935–947 (2025).

    Article  CAS  PubMed  Google Scholar 

  99. Pawlak, K., Myśliwiec, M. & Pawlak, D. Kynurenine pathway — a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients. Adv. Med. Sci. 55, 196–203 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. Mohiti, S., Alizadeh, E., Bisgaard, L. S., Ebrahimi-Mameghani, M. & Christoffersen, C. The AhR/P38 MAPK pathway mediates kynurenine-induced cardiomyocyte damage: the dual role of resveratrol in apoptosis and autophagy. Biomed. Pharmacother. 186, 118015 (2025).

    Article  CAS  PubMed  Google Scholar 

  101. Carrillo-Mora, P. et al. Kynurenines and inflammation: a remarkable axis for multiple sclerosis treatment. Pharmaceuticals 17, 983 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Isakova, T. et al. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA 305, 2432–2439 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Lau, W. L., Kalantar-Zadeh, K., Kovesdy, C. P. & Mehrotra, R. Alkaline phosphatase: better than PTH as a marker of cardiovascular and bone disease? Hemodial. Int. 18, 720–724 (2014).

    Article  PubMed  Google Scholar 

  104. Fuchs, M. A. A. et al. Fibroblast growth factor 23 and fibroblast growth factor receptor 4 promote cardiac metabolic remodeling in chronic kidney disease. Kidney Int. 107, 852–868 (2025).

    Article  CAS  PubMed  Google Scholar 

  105. Leifheit-Nestler, M. et al. Fibroblast growth factor 23 is induced by an activated renin-angiotensin-aldosterone system in cardiac myocytes and promotes the pro-fibrotic crosstalk between cardiac myocytes and fibroblasts. Nephrol. Dial. Transplant. 33, 1722–1734 (2018).

    Article  CAS  PubMed  Google Scholar 

  106. Saito, T. et al. Fibroblast growth factor 23 exacerbates cardiac fibrosis in deoxycorticosterone acetate-salt mice with hypertension. Lab. Invest. 103, 100003 (2023).

    Article  CAS  PubMed  Google Scholar 

  107. Guo, L. W., Wang, Y. K., Li, S. J., Yin, G. T. & Li, D. Elevated fibroblast growth factor 23 impairs endothelial function through the NF-κB signaling pathway. J. Atheroscler. Thromb. 30, 138–149 (2023).

    Article  CAS  PubMed  Google Scholar 

  108. Vergara, N. et al. The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function. Nephrol. Dial. Transplant. 38, 322–343 (2023).

    Article  CAS  PubMed  Google Scholar 

  109. Yang, K. et al. Fibroblast growth factor 23 weakens chemotaxis of human blood neutrophils in microfluidic devices. Sci. Rep. 7, 3100 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  110. Chen, S. M. et al. Hydrogen sulfide attenuates β2-microglobulin-induced cognitive dysfunction: involving recovery of hippocampal autophagic flux. Front. Behav. Neurosci. 13, 244 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Andoh, T., Maki, T., Li, S. & Uta, D. β2-microglobulin elicits itch-related responses in mice through the direct activation of primary afferent neurons expressing transient receptor potential vanilloid 1. Eur. J. Pharmacol. 810, 134–140 (2017).

    Article  CAS  PubMed  Google Scholar 

  112. Li, S., Andoh, T., Zhang, Q., Uta, D. & Kuraishi, Y. β2-microglobulin, interleukin-31, and arachidonic acid metabolites (leukotriene B4 and thromboxane A2) are involved in chronic renal failure-associated itch-associated responses in mice. Eur. J. Pharmacol. 847, 19–25 (2019).

    Article  CAS  PubMed  Google Scholar 

  113. Knopp, T. et al. Myeloid cell-derived interleukin-6 induces vascular dysfunction and vascular and systemic inflammation. Eur. Heart J. Open 4, oeae046 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  114. Keefe, J. A. et al. Macrophage-mediated interleukin-6 signaling drives ryanodine receptor-2 calcium leak in postoperative atrial fibrillation. J. Clin. Invest. 135, e187711 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Pergola, P. E. et al. Ziltivekimab for treatment of anemia of inflammation in patients on hemodialysis: results from a phase 1/2 multicenter, randomized, double-blind, placebo-controlled trial. J. Am. Soc. Nephrol. 32, 211–222 (2021).

    Article  CAS  PubMed  Google Scholar 

  116. Durlacher-Betzer, K. et al. Interleukin-6 contributes to the increase in fibroblast growth factor 23 expression in acute and chronic kidney disease. Kidney Int. 94, 315–325 (2018).

    Article  CAS  PubMed  Google Scholar 

  117. Velloso, F. J., Zaritsky, R., Houbeika, R. Y., Rios, N. & Levison, S. W. Interleukin-6 produces behavioral deficits in pre-pubescent mice independent of neuroinflammation. Brain, Behav. Immun. 126, 275–288 (2025).

    Article  CAS  PubMed  Google Scholar 

  118. Keshari, S. et al. IL-6/p-BTK/p-ERK signaling mediates calcium phosphate-induced pruritus. FASEB J. 33, 12036–12046 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Meyer, T. W. & Hostetter, T. H. Uremia. N. Engl. J. Med. 357, 1316–1325 (2007).

    Article  CAS  PubMed  Google Scholar 

  120. Hénaut, L., Mary, A., Chillon, J. M., Kamel, S. & Massy, Z. A. The impact of uremic toxins on vascular smooth muscle cell function. Toxins 10, 218 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Evenepoel, P., Stenvinkel, P., Shanahan, C. & Pacifici, R. Inflammation and gut dysbiosis as drivers of CKD-MBD. Nat. Rev. Nephrol. 19, 646–657 (2023).

    Article  PubMed  Google Scholar 

  122. Kolachalama, V. B. et al. Uremic solute-aryl hydrocarbon receptor-tissue factor axis associates with thrombosis after vascular injury in humans. J. Am. Soc. Nephrol. 29, 1063–1072 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Arinze, N. V. et al. Tryptophan metabolites suppress the Wnt pathway and promote adverse limb events in chronic kidney disease. J. Clin. Invest. 132, e142260 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Hung, S. C. et al. Indoxyl sulfate suppresses endothelial progenitor cell-mediated neovascularization. Kidney Int. 89, 574–585 (2016).

    Article  CAS  PubMed  Google Scholar 

  125. Chermiti, R., Burtey, S. & Dou, L. Role of uremic toxins in vascular inflammation associated with chronic kidney disease. J. Clin. Med. 13, 7149 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Santana Machado, T., Cerini, C. & Burtey, S. Emerging roles of aryl hydrocarbon receptors in the altered clearance of drugs during chronic kidney disease. Toxins 11, 209 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Bock, K. W. Aryl hydrocarbon receptor (AHR)-mediated inflammation and resolution: non-genomic and genomic signaling. Biochem. Pharmacol. 182, 114220 (2020).

    Article  CAS  PubMed  Google Scholar 

  128. Ravid, J. D., Kamel, M. H. & Chitalia, V. C. Uraemic solutes as therapeutic targets in CKD-associated cardiovascular disease. Nat. Rev. Nephrol. 17, 402–416 (2021).

    Article  CAS  PubMed  Google Scholar 

  129. Addi, T. et al. Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells. Arch. Toxicol. 93, 121–136 (2019).

    Article  CAS  PubMed  Google Scholar 

  130. Merchak, A. R. et al. The activity of the aryl hydrocarbon receptor in T cells tunes the gut microenvironment to sustain autoimmunity and neuroinflammation. PLoS Biol. 21, e3002000 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Lamas, B. et al. Aryl hydrocarbon receptor ligand production by the gut microbiota is decreased in celiac disease leading to intestinal inflammation. Sci. Transl. Med. 12, eaba0624 (2020).

    Article  CAS  PubMed  Google Scholar 

  132. Wiggins, B. G. et al. Endothelial sensing of AHR ligands regulates intestinal homeostasis. Nature 621, 821–829 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Schnabl, B., Damman, C. J. & Carr, R. M. Metabolic dysfunction-associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations. J. Clin. Investig. 135, e186423 (2025).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Dou, L. et al. Aryl hydrocarbon receptor is activated in patients and mice with chronic kidney disease. Kidney Int. 93, 986–999 (2018).

    Article  CAS  PubMed  Google Scholar 

  135. Evenepoel, P., Bover, J. & Ureña Torres, P. Parathyroid hormone metabolism and signaling in health and chronic kidney disease. Kidney Int. 90, 1184–1190 (2016).

    Article  CAS  PubMed  Google Scholar 

  136. Sinha, A. K. et al. Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota. Nat. Microbiol. 9, 1964–1978 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Seymour, B. J. et al. Microbiota-dependent indole production stimulates the development of collagen-induced arthritis in mice. J. Clin. Invest. 134, e167671 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Vaziri, N. D., Oveisi, F., Wierszbiezki, M., Shaw, V. & Sporty, L. D. Serum melatonin and 6-sulfatoxymelatonin in end-stage renal disease: effect of hemodialysis. Artif. Organs 17, 764–769 (1993).

    Article  CAS  PubMed  Google Scholar 

  139. Takahashi, R. et al. The significance of NAD + metabolites and nicotinamide N-methyltransferase in chronic kidney disease. Sci. Rep. 12, 6398 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Walker, J. A. et al. Indoleamine 2,3-dioxygenase-1, a novel therapeutic target for post-vascular injury thrombosis in CKD. J. Am. Soc. Nephrol. 32, 2834–2850 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Mair, R. D., Sirich, T. L., Plummer, N. S. & Meyer, T. W. Characteristics of colon-derived uremic solutes. Clin. J. Am. Soc. Nephrol. 13, 1398–1404 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Nemet, I. et al. Microbe-derived uremic solutes enhance thrombosis potential in the host. mBio 14, e0133123 (2023).

    Article  PubMed  Google Scholar 

  143. Nemet, I. et al. Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality. Eur. Heart J. 44, 3085–3096 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Tang, W. H. et al. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ. Res. 116, 448–455 (2015).

    Article  CAS  PubMed  Google Scholar 

  145. Chapron, A. et al. Does secretory clearance follow glomerular filtration rate in chronic kidney diseases? Reconsidering the intact nephron hypothesis. Clin. Transl. Sci. 10, 395–403 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Lowenstein, J. & Grantham, J. J. Residual renal function: a paradigm shift. Kidney Int. 91, 561–565 (2017).

    Article  PubMed  Google Scholar 

  147. Cohen, G. et al. Review on uraemic toxins III: recommendations for handling uraemic retention solutes in vitro — towards a standardized approach for research on uraemia. Nephrol. Dial. Transplant. 22, 3381–3390 (2007).

    Article  CAS  PubMed  Google Scholar 

  148. Schulman, G. et al. Randomized placebo-controlled EPPIC trials of AST-120 in CKD. J. Am. Soc. Nephrol. 26, 1732–1746 (2015).

    Article  CAS  PubMed  Google Scholar 

  149. Su, P. Y. et al. Efficacy of AST-120 for patients with chronic kidney disease: a network meta-analysis of randomized controlled trials. Front. Pharmacol. 12, 676345 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Pietrement, C., Gorisse, L., Jaisson, S. & Gillery, P. Chronic increase of urea leads to carbamylated proteins accumulation in tissues in a mouse model of CKD. PLoS ONE 8, e82506 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  151. Verbrugge, F. H., Tang, W. H. & Hazen, S. L. Protein carbamylation and cardiovascular disease. Kidney Int. 88, 474–478 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Miyata, T., Kurokawa, K. & van Ypersele de Strihou, C. Relevance of oxidative and carbonyl stress to long-term uremic complications. Kidney Int. Suppl. 76, S120–S125 (2000).

    Article  CAS  PubMed  Google Scholar 

  153. Soulage, C. O. et al. Two toxic lipid aldehydes, 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), accumulate in patients with chronic kidney disease. Toxins 12, 567 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Agalou, S., Ahmed, N., Babaei-Jadidi, R., Dawnay, A. & Thornalley, P. J. Profound mishandling of protein glycation degradation products in uremia and dialysis. J. Am. Soc. Nephrol. 16, 1471–1485 (2005).

    Article  CAS  PubMed  Google Scholar 

  155. Rabbani, N., Sebekova, K., Sebekova, K. Jr., Heidland, A. & Thornalley, P. J. Accumulation of free adduct glycation, oxidation, and nitration products follows acute loss of renal function. Kidney Int. 72, 1113–1121 (2007).

    Article  CAS  PubMed  Google Scholar 

  156. Liu, Z., Yang, J., Du, M. & Xin, W. Functioning and mechanisms of PTMs in renal diseases. Front. Pharmacol. 14, 1238706 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Hermann, J., Schurgers, L. & Jankowski, V. Identification and characterization of post-translational modifications: clinical implications. Mol. Aspects Med. 86, 101066 (2022).

    Article  CAS  PubMed  Google Scholar 

  158. Bradley, D. The evolution of post-translational modifications. Curr. Opin. Genet. Dev. 76, 101956 (2022).

    Article  CAS  PubMed  Google Scholar 

  159. Delporte, C. et al. Myeloperoxidase-catalyzed oxidation of cyanide to cyanate: a potential carbamylation route involved in the formation of atherosclerotic plaques? J. Biol. Chem. 293, 6374–6386 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Jankowski, V. et al. Carbamylated sortilin associates with cardiovascular calcification in patients with chronic kidney disease. Kidney Int. 101, 574–584 (2022).

    Article  CAS  PubMed  Google Scholar 

  161. Speer, T. et al. Carbamylated low-density lipoprotein induces endothelial dysfunction. Eur. Heart J. 35, 3021–3032 (2014).

    Article  CAS  PubMed  Google Scholar 

  162. Kalim, S. et al. Protein carbamylation and chronic kidney disease progression in the Chronic Renal Insufficiency Cohort Study. Nephrol. Dial. Transplant. 37, 139–147 (2021).

    Article  PubMed  Google Scholar 

  163. Tang, M. et al. The impact of carbamylation and anemia on HbA1c’s association with renal outcomes in patients with diabetes and chronic kidney disease. Diabetes Care 46, 130–137 (2023).

    Article  CAS  PubMed  Google Scholar 

  164. Rueth, M. et al. Guanidinylations of albumin decreased binding capacity of hydrophobic metabolites. Acta Physiol. 215, 13–23 (2015).

    Article  CAS  Google Scholar 

  165. Apostolov, E. O., Ray, D., Savenka, A. V., Shah, S. V. & Basnakian, A. G. Chronic uremia stimulates LDL carbamylation and atherosclerosis. J. Am. Soc. Nephrol. 21, 1852–1857 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  166. Bonnin-Marquez, A. et al. Guanidinylation compromises the anti-inflammatory and anti-oxidative properties of apolipoprotein A-I in chronic kidney disease progression. Kidney Int. 107, 916–929 (2025).

    Article  CAS  PubMed  Google Scholar 

  167. Schunk, S. J. et al. Guanidinylated apolipoprotein C3 (ApoC3) associates with kidney and vascular injury. J. Am. Soc. Nephrol. 32, 3146–3160 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Zewinger, S. et al. Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat. Immunol. 21, 30–41 (2020).

    Article  CAS  PubMed  Google Scholar 

  169. Schuett, K. et al. Clot structure: a potent mortality risk factor in patients on hemodialysis. J. Am. Soc. Nephrol. 28, 1622–1630 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  170. Jankowski, V., Lellig, M. & Jankowski, J. WCN24-66 Post-translational guanidinylation of the HDL protein ApoA-1. Kidney Int. Rep. 9, S658 (2024).

    Google Scholar 

  171. Tölle, M. et al. High-density lipoprotein loses its anti-inflammatory capacity by accumulation of pro-inflammatory-serum amyloid A. Cardiovasc. Res. 94, 154–162 (2012).

    Article  PubMed  Google Scholar 

  172. Ebert, T. et al. Inflammation and oxidative stress in chronic kidney disease and dialysis patients. Antioxid. Redox Signal. 35, 1426–1448 (2021).

    Article  CAS  PubMed  Google Scholar 

  173. Juan, C. A., Pérez de la Lastra, J. M., Plou, F. J. & Pérez-Lebeña, E. The chemistry of reactive oxygen species (ROS) revisited: outlining their role in biological macromolecules (DNA, lipids and proteins) and induced pathologies. Int. J. Mol. Sci. 22, 4642 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  174. Florens, N. et al. CKD increases carbonylation of HDL and is associated with impaired antiaggregant properties. J. Am. Soc. Nephrol. 31, 1462–1477 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Hoffman, S. et al. Thiol redox chemistry: role of protein cysteine oxidation and altered redox homeostasis in allergic inflammation and asthma. J. Cell. Biochem. 116, 884–892 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Amiya, E. Interaction of hyperlipidemia and reactive oxygen species: Insights from the lipid-raft platform. World J. Cardiol. 8, 689–694 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  177. Reyes, C. et al. Loxin reduced the inflammatory response in the liver and the aortic fatty streak formation in mice fed with a high-fat diet. Int. J. Mol. Sci. 23, 7329 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  178. Zhang, Q. et al. High glucose/ox-LDL induced hepatic sinusoidal capillarization via αvβ5/FAK/ERK signaling pathway. Biochem. Biophys. Res. Commun. 513, 1055–1062 (2019).

    Article  CAS  PubMed  Google Scholar 

  179. Besler, C., Lüscher, T. F. & Landmesser, U. Molecular mechanisms of vascular effects of high-density lipoprotein: alterations in cardiovascular disease. EMBO Mol. Med. 4, 251–268 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Nakajima, T. et al. Localization of oxidized HDL in atheromatous plaques and oxidized HDL binding sites on human aortic endothelial cells. Ann. Clin. Biochem. 37, 179–186 (2000).

    Article  CAS  PubMed  Google Scholar 

  181. Thorne, R. F., Mhaidat, N. M., Ralston, K. J. & Burns, G. F. CD36 is a receptor for oxidized high density lipoprotein: implications for the development of atherosclerosis. FEBS Lett. 581, 1227–1232 (2007).

    Article  CAS  PubMed  Google Scholar 

  182. Glorieux, G., Gryp, T. & Perna, A. Gut-derived metabolites and their role in immune dysfunction in chronic kidney disease. Toxins 12, 245 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  183. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. 105, S117–S314 (2024).

    Article  Google Scholar 

  184. Billing, A. M. et al. Metabolic communication by SGLT2 inhibition. Circulation 149, 860–884 (2024).

    Article  CAS  PubMed  Google Scholar 

  185. He, L. et al. Canagliflozin attenuates kidney injury, gut-derived toxins, and gut microbiota imbalance in high-salt diet-fed Dahl salt-sensitive rats. Ren. Fail. 46, 2300314 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  186. Matsui, A. et al. Canagliflozin protects the cardiovascular system through effects on the gut environment in non-diabetic nephrectomized rats. Clin. Exp. Nephrol. 27, 295–308 (2023).

    Article  CAS  PubMed  Google Scholar 

  187. Mishima, E. et al. Canagliflozin reduces plasma uremic toxins and alters the intestinal microbiota composition in a chronic kidney disease mouse model. Am. J. Physiol. Renal Physiol. 315, F824–F833 (2018).

    Article  CAS  PubMed  Google Scholar 

  188. Sokolov, V. et al. Differentiating the sodium-glucose cotransporter 1 inhibition capacity of canagliflozin vs. dapagliflozin and empagliflozin using quantitative systems pharmacology modeling. CPT Pharmacometrics Syst. Pharmacol. 9, 222–229 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Sun, C. Y., Chang, S. C. & Wu, M. S. Uremic toxins induce kidney fibrosis by activating intrarenal renin-angiotensin-aldosterone system associated epithelial-to-mesenchymal transition. PLoS ONE 7, e34026 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  190. Iguchi, A. et al. Effect of sucroferric oxyhydroxide on gastrointestinal microbiome and uremic toxins in patients with chronic kidney disease undergoing hemodialysis. Clin. Exp. Nephrol. 24, 725–733 (2020).

    Article  CAS  PubMed  Google Scholar 

  191. Lau, W. L. et al. The phosphate binder ferric citrate alters the gut microbiome in rats with chronic kidney disease. J. Pharmacol. Exp. Ther. 367, 452–460 (2018).

    Article  CAS  PubMed  Google Scholar 

  192. Laville, S. M. et al. Intestinal chelators, sorbants, and gut-derived uremic toxins. Toxins 13, 91 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Aronov, P. A. et al. Colonic contribution to uremic solutes. J. Am. Soc. Nephrol. 22, 1769–1776 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  194. Lee, J. et al. Antibiotic-induced intestinal microbiota depletion can attenuate the acute kidney injury to chronic kidney disease transition via NADPH oxidase 2 and trimethylamine-N-oxide inhibition. Kidney Int. 105, 1239–1253 (2024).

    Article  CAS  PubMed  Google Scholar 

  195. Nazzal, L. et al. Effect of vancomycin on the gut microbiome and plasma concentrations of gut-derived uremic solutes. Kidney Int. Rep. 6, 2122–2133 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Sumida, K., Lau, W. L., Kalantar-Zadeh, K. & Kovesdy, C. P. Novel intestinal dialysis interventions and microbiome modulation to control uremia. Curr. Opin. Nephrol. Hypertens. 31, 82–91 (2022).

    Article  CAS  PubMed  Google Scholar 

  197. Roager, H. M. et al. Colonic transit time is related to bacterial metabolism and mucosal turnover in the gut. Nat. Microbiol. 1, 16093 (2016).

    Article  CAS  PubMed  Google Scholar 

  198. Kim, K., Cho, W. H., Hwang, S. D., Lee, S. W. & Song, J. H. Association between constipation and incident chronic kidney disease in the UK Biobank study. Sci. Rep. 14, 32106 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  199. Sumida, K. et al. Constipation and incident CKD. J. Am. Soc. Nephrol. 28, 1248–1258 (2017).

    Article  CAS  PubMed  Google Scholar 

  200. Sumida, K. et al. Laxative use in patients with advanced chronic kidney disease transitioning to dialysis. Nephrol. Dial. Transplant. 36, 2018–2026 (2021).

    Article  CAS  PubMed  Google Scholar 

  201. Nanto-Hara, F. et al. The guanylate cyclase C agonist linaclotide ameliorates the gut-cardio-renal axis in an adenine-induced mouse model of chronic kidney disease. Nephrol. Dial. Transplant. 35, 250–264 (2020).

    Article  CAS  PubMed  Google Scholar 

  202. Sueyoshi, M. et al. Effects of lactulose on renal function and gut microbiota in adenine-induced chronic kidney disease rats. Clin. Exp. Nephrol. 23, 908–919 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  203. Benech, N. & Koppe, L. Is there a place for faecal microbiota transplantation in chronic kidney disease? Nephrol. Dial. Transplant. 37, 2303–2306 (2022).

    Article  CAS  PubMed  Google Scholar 

  204. Schulman, G. et al. The effects of AST-120 on chronic kidney disease progression in the United States of America: a post hoc subgroup analysis of randomized controlled trials. BMC Nephrol. 17, 141 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  205. Abe, H. & Otsuka, M. Comparison of physico-chemical characteristics among three pharmaceutical spherical carbon adsorbents. Colloids Surf. B Biointerfaces 100, 90–94 (2012).

    Article  CAS  PubMed  Google Scholar 

  206. Kato, S. et al. Zirconium-based metal-organic frameworks for the removal of protein-bound uremic toxin from human serum albumin. J. Am. Chem. Soc. 141, 2568–2576 (2019).

    Article  CAS  PubMed  Google Scholar 

  207. Wei, J. et al. Efficient selective removal of uremic toxin precursor by olefin-linked covalent organic frameworks for nephropathy treatment. Nat. Commun. 14, 2805 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  208. Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585–1595 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  209. Graboski, A. L. et al. Mechanism-based inhibition of gut microbial tryptophanases reduces serum indoxyl sulfate. Cell Chem. Biol. 30, 1402–1413.e7 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  210. Shashar, M. et al. Targeting STUB1-tissue factor axis normalizes hyperthrombotic uremic phenotype without increasing bleeding risk. Sci. Transl. Med. 9, eaam8475 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  211. Stockinger, B., Shah, K. & Wincent, E. AHR in the intestinal microenvironment: safeguarding barrier function. Nat. Rev. Gastroenterol. Hepatol. 18, 559–570 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Cotillard, A. et al. Dietary intervention impact on gut microbial gene richness. Nature 500, 585–588 (2013).

    Article  CAS  PubMed  Google Scholar 

  213. De Filippo, C. et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc. Natl Acad. Sci. USA 107, 14691–14696 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  214. Gill, S. R. et al. Metagenomic analysis of the human distal gut microbiome. Science 312, 1355–1359 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  215. Ikizler, T. A. et al. KDOQI clinical practice guideline for nutrition in CKD: 2020 update. Am. J. Kidney Dis. 76, S1–s107 (2020).

    Article  CAS  PubMed  Google Scholar 

  216. Kalantar-Zadeh, K. & Fouque, D. Nutritional management of chronic kidney disease. N. Engl. J. Med. 377, 1765–1776 (2017).

    Article  CAS  PubMed  Google Scholar 

  217. Koppe, L. & Soulage, C. O. The impact of dietary nutrient intake on gut microbiota in the progression and complications of chronic kidney disease. Kidney Int. 102, 728–739 (2022).

    Article  CAS  PubMed  Google Scholar 

  218. Carrero, J. J. et al. Plant-based diets to manage the risks and complications of chronic kidney disease. Nat. Rev. Nephrol. 16, 525–542 (2020).

    Article  PubMed  Google Scholar 

  219. Koppe, L., Fouque, D. & Soulage, C. O. The role of gut microbiota and diet on uremic retention solutes production in the context of chronic kidney disease. Toxins 10, 155 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  220. Letourneau, P., Bataille, S., Chauveau, P., Fouque, D. & Koppe, L. Source and composition in amino acid of dietary proteins in the primary prevention and treatment of CKD. Nutrients 12, 3892 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  221. Koppe, L., Cassani de Oliveira, M. & Fouque, D. Ketoacid analogues supplementation in chronic kidney disease and future perspectives. Nutrients 11, 2071 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  222. Stanford, J. et al. High-diversity plant-based diet and gut microbiome, plasma metabolome, and symptoms in adults with CKD. Clin. J. Am. Soc. Nephrol. 20, 619–631 (2025).

    Article  PubMed  Google Scholar 

  223. Stanford, J. et al. Associations among plant-based diet quality, uremic toxins, and gut microbiota profile in adults undergoing hemodialysis therapy. J. Ren. Nutr. 31, 177–188 (2021).

    Article  CAS  PubMed  Google Scholar 

  224. Hu, E. A. et al. Adherence to healthy dietary patterns and risk of CKD progression and all-cause mortality: findings from the CRIC (Chronic Renal Insufficiency Cohort) study. Am. J. Kidney Dis. 77, 235–244 (2021).

    Article  CAS  PubMed  Google Scholar 

  225. Kelly, J. T. et al. Healthy dietary patterns and risk of mortality and ESRD in CKD: a meta-analysis of cohort studies. Clin. J. Am. Soc. Nephrol. 12, 272–279 (2017).

    Article  PubMed  Google Scholar 

  226. Podadera-Herreros, A. et al. Long-term consumption of a Mediterranean diet or a low-fat diet on kidney function in coronary heart disease patients: the CORDIOPREV randomized controlled trial. Clin. Nutr. 41, 552–559 (2022).

    Article  CAS  PubMed  Google Scholar 

  227. Yoshifuji, A. et al. Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats. Nephrol. Dial. Transplant. 31, 401–412 (2016).

    Article  CAS  PubMed  Google Scholar 

  228. Barba, C. et al. A low aromatic amino-acid diet improves renal function and prevent kidney fibrosis in mice with chronic kidney disease. Sci. Rep. 11, 19184 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  229. Lobel, L., Cao, Y. G., Fenn, K., Glickman, J. N. & Garrett, W. S. Diet posttranslationally modifies the mouse gut microbial proteome to modulate renal function. Science 369, 1518–1524 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  230. Wang, X. et al. Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents. Gut 69, 2131–2142 (2020).

    Article  CAS  PubMed  Google Scholar 

  231. Mafra, D. et al. Food as medicine: targeting the uraemic phenotype in chronic kidney disease. Nat. Rev. Nephrol. 17, 153–171 (2021).

    Article  PubMed  Google Scholar 

  232. Whelan, K., Bancil, A. S., Lindsay, J. O. & Chassaing, B. Ultra-processed foods and food additives in gut health and disease. Nat. Rev. Gastroenterol. Hepatol. 21, 406–427 (2024).

    Article  PubMed  Google Scholar 

  233. Koppe, L. & Fouque, D. Microbiota and prebiotics modulation of uremic toxin generation. Panminerva Med. 59, 173–187 (2017).

    Article  PubMed  Google Scholar 

  234. Koppe, L., Mafra, D. & Fouque, D. Probiotics and chronic kidney disease. Kidney Int. 88, 958–966 (2015).

    Article  CAS  PubMed  Google Scholar 

  235. Cooper, T. E. et al. Synbiotics, prebiotics and probiotics for people with chronic kidney disease. Cochrane Database Syst. Rev. 10, CD013631 (2023).

    PubMed  Google Scholar 

  236. Liu, C., Yang, L., Wei, W. & Fu, P. Efficacy of probiotics/synbiotics supplementation in patients with chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials. Front. Nutr. 11, 1434613 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  237. Liu, J. et al. Biotic supplements in patients with chronic kidney disease: meta-analysis of randomized controlled trials. J. Ren. Nutr. 32, 10–21 (2022).

    Article  PubMed  Google Scholar 

  238. Ribeiro, F. P. B., de Luna Freire, M. O., de Oliveira Coutinho, D., de Santana Cirilo, M. A. & de Brito Alves, J. L. Gut dysbiosis and probiotic therapy in chronic kidney disease: a comprehensive review. Probiotics Antimicrob. Proteins 17, 1797–1819 (2025).

    Article  CAS  PubMed  Google Scholar 

  239. Voroneanu, L. et al. Gut microbiota in chronic kidney disease: from composition to modulation towards better outcomes-a systematic review. J. Clin. Med. 12, 1948 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  240. More, S. et al. Evaluation of existing guidelines for their adequacy for the food and feed risk assessment of microorganisms obtained through synthetic biology. EFSA 20, e07479 (2022).

    Google Scholar 

  241. Cao, J. et al. Lactobacillus paracasei X11 ameliorates hyperuricemia and modulates gut microbiota in mice. Front. Immunol. 13, 940228 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  242. Li, H. B. et al. Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis. Circulation Res. 131, e120–e134 (2022).

    Article  CAS  PubMed  Google Scholar 

  243. Zhu, H. et al. The probiotic L. casei Zhang slows the progression of acute and chronic kidney disease. Cell Metab. 33, 2091–2093 (2021).

    Article  CAS  PubMed  Google Scholar 

  244. Magnani, S. & Atti, M. Uremic toxins and blood purification: a review of current evidence and future perspectives. Toxins 13, 246 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  245. de Vries, J. C. et al. Evidence on continuous flow peritoneal dialysis: a review. Semin. Dial. 35, 481–497 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  246. Sánchez-Ospina, D. et al. Displacing the burden: a review of protein-bound uremic toxin clearance strategies in chronic kidney disease. J. Clin. Med. 13, 1428 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  247. Blankestijn, P. J. et al. Effect of hemodiafiltration or hemodialysis on mortality in kidney failure. N. Engl. J. Med. 389, 700–709 (2023).

    Article  CAS  PubMed  Google Scholar 

  248. Grooteman, M. P. et al. Effect of online hemodiafiltration on all-cause mortality and cardiovascular outcomes. J. Am. Soc. Nephrol. 23, 1087–1096 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  249. van Gelder, M. K. et al. Protein-bound uremic toxins in hemodialysis patients relate to residual kidney function, are not influenced by convective transport, and do not relate to outcome. Toxins 12, 234 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  250. Fiorentino, M., La Fergola, F. & De Rosa, S. Medium cut-off dialyzer for middle molecular uremic toxins in AKI and chronic dialysis. J. Nephrol. 37, 23–37 (2024).

    Article  CAS  PubMed  Google Scholar 

  251. Maduell, F. et al. Comparison of four medium cut-off dialyzers. Clin. Kidney J. 15, 2292–2299 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  252. Eloot, S. et al. Impact of hemodialysis duration on the removal of uremic retention solutes. Kidney Int. 73, 765–770 (2008).

    Article  CAS  PubMed  Google Scholar 

  253. Furue, M. & Tsuji, G. Chloracne and hyperpigmentation caused by exposure to hazardous aryl hydrocarbon receptor ligands. Int. J. Environ. Res. Public. Health 16, 4864 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. GBD 2021 Forecasting Collaborators Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the global burden of disease study 2021. Lancet 403, 2204–2256 (2024).

    Article  Google Scholar 

  255. Ramada, D. L. et al. Portable, wearable and implantable artificial kidney systems: needs, opportunities and challenges. Nat. Rev. Nephrol. 19, 481–490 (2023).

    Article  PubMed  Google Scholar 

  256. Ghosh, A. et al. Effective clearance of uremic toxins using functionalised silicon Nanoporous membranes. Biomed. Microdevices 23, 4 (2021).

    Article  CAS  PubMed  Google Scholar 

  257. Zhang, Q., Lu, X., Yang, S., Zhang, Q. & Zhao, L. Preparation of anticoagulant polyvinylidene fluoride hollow fiber hemodialysis membranes. Biomed. Tech. 62, 57–65 (2017).

    Article  Google Scholar 

  258. Kim, D. & Stamatialis, D. High flux mixed matrix membrane with low albumin leakage for blood plasma detoxification. J. Membr. Sci. 609, 118187 (2020).

    Article  CAS  Google Scholar 

  259. Maheshwari, V., Tao, X., Thijssen, S. & Kotanko, P. Removal of protein-bound uremic toxins using binding competitors in hemodialysis: a narrative review. Toxins 13, 622 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  260. Shi, Y. et al. Removal of protein-bound uremic toxins by liposome-supported peritoneal dialysis. Perit. Dial. Int. 39, 509–518 (2019).

    Article  CAS  PubMed  Google Scholar 

  261. Raillon, L. A. et al. Medium chain fatty acids are potent binding competitors to improve protein-bound uremic toxin clearance during hemodialysis. Kidney Int. 108, 411–426 (2025).

    Article  CAS  PubMed  Google Scholar 

  262. Devlin, A. S. et al. Modulation of a circulating uremic solute via rational genetic manipulation of the gut microbiota. Cell Host Microbe 20, 709–715 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  263. Lubkowicz, D., Hava, D. L., Lewis, K. & Isabella, V. M. Rational engineering of Escherichia coli Nissle 1917 as live biotherapeutic to degrade uremic toxin precursors. ACS Synth. Biol. 13, 1077–1084 (2024).

    Article  CAS  PubMed  Google Scholar 

  264. De Chiara, F., Ferret-Miñana, A., Fernández-Costa, J. M. & Ramón-Azcón, J. The tissue engineering revolution: from bench research to clinical reality. Biomedicines 12, 453 (2024).

    Article  PubMed  PubMed Central  Google Scholar 

  265. Freedman, B. S. & Dekel, B. Engraftment of kidney organoids in vivo. Curr. Transplant. Rep. 10, 29–39 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  266. Milani, N., Parrott, N., Galetin, A., Fowler, S. & Gertz, M. In silico modeling and simulation of organ-on-a-chip systems to support data analysis and a priori experimental design. CPT Pharmacometrics Syst. Pharmacol. 13, 524–543 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  267. Lopes, M. B. et al. The omics-driven machine learning path to cost-effective precision medicine in chronic kidney disease. Proteomics 11–12, e202400108 (2025).

    Article  Google Scholar 

  268. Aiyegbusi, O. L. et al. Measurement properties of patient-reported outcome measures (PROMs) used in adult patients with chronic kidney disease: a systematic review. PLoS ONE 12, e0179733 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  269. Tong, A. et al. Implementing core outcomes in kidney disease: report of the standardized outcomes in nephrology (SONG) implementation workshop. Kidney Int. 94, 1053–1068 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  270. Aranda-Rivera, A. K., Cruz-Gregorio, A., Aparicio-Trejo, O. E. & Pedraza-Chaverri, J. Mitochondrial redox signaling and oxidative stress in kidney diseases. Biomolecules 11, 1144 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  271. Kehm, R., Baldensperger, T., Raupbach, J. & Höhn, A. Protein oxidation — formation mechanisms, detection and relevance as biomarkers in human diseases. Redox Biol. 42, 101901 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  272. Suzuki, Y. J. Oxidant-mediated protein amino acid conversion. Antioxidants 8, 50 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the members of the EUTox work group for their ideas, research, discussions and efforts in standardizing uraemic toxin-related research: A. Argiles, Montpellier, France; J. Beige, Leipzig, Germany; P. Brunet, Marseille, France; J.-M. Chillon, Amiens, France; G. Cohen, Vienna, Austria; O. Abou Deif, Hamburg, Germany; D. Fliser, Homburg/Saar, Germany; I. Fridolin, Tallinn, Estonia; V. Jankowski, Aachen, Germany; Z. A. Massy, Paris, France; H. Mischak, Hannover, Germany; A. Ortiz, Madrid, Spain; A. Perna, Naples, Italy; J. Mariano Rodriguez-Portillo, Cordoba, Spain; J. Schanstra, Toulouse, France; J. Siwy, Hannover, Germany; G. Spasovski, Skopje, Republic of North Macedonia; D. Stamatialis, Twente, The Netherlands; B. G. Stegmayr, Umea, Sweden; P. Stenvinkel, Stockholm, Sweden; R. Stojanov, Skopje, Republic of North Macedonia; A. Vlahou, Athens, Greece; and A. Wiecek, Katowice, Poland. All authors are members of the EUTox work group. J.J. is supported by grants from the Interdisciplinary Center for Clinical Research within the Faculty of Medicine at the RWTH Aachen University and the ‘Deutsche Forschungsgemeinschaft‘ (DFG, German Research Foundation) by the Transregional Collaborative Research Centre (Project-ID 322900939), INST 948/4S-1, CRU 5011 (Project-ID 445703531) and IZKF FACROSS and Phase Transition in Disease (1-1) of the University of Aachen (Germany) Cost-Action CA 21165, ERA-PerMed (ERA-PERMED2022-202-KidneySign).

Author information

Authors and Affiliations

  1. Department of Internal Medicine and Pediatrics, Nephrology Section, Ghent University Hospital, Ghent, Belgium

    Griet Glorieux & Raymond Vanholder

  2. Faculty of Pharmacy, Aix Marseille University, INSERM, INRAE, Marseille, France

    Stéphane Burtey

  3. Department of Microbiology, Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven, Leuven, Belgium

    Pieter Evenepoel

  4. Institute for Molecular Cardiovascular Research, Medical Faculty, RWTH Aachen University, Aachen, Germany

    Joachim Jankowski

  5. Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht, Maastricht, The Netherlands

    Joachim Jankowski

  6. CarMeN Laboratory, INSERM, INRAE, Claude Bernard Lyon 1 University, Pierre-Bénite, France

    Laetitia Koppe

  7. Department of Nephrology and Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France

    Laetitia Koppe

  8. Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands

    Rosalinde Masereeuw

Authors
  1. Griet Glorieux
    View author publications

    Search author on:PubMed Google Scholar

  2. Stéphane Burtey
    View author publications

    Search author on:PubMed Google Scholar

  3. Pieter Evenepoel
    View author publications

    Search author on:PubMed Google Scholar

  4. Joachim Jankowski
    View author publications

    Search author on:PubMed Google Scholar

  5. Laetitia Koppe
    View author publications

    Search author on:PubMed Google Scholar

  6. Rosalinde Masereeuw
    View author publications

    Search author on:PubMed Google Scholar

  7. Raymond Vanholder
    View author publications

    Search author on:PubMed Google Scholar

Contributions

All authors researched data for the article, made substantial contributions to discussions of the content and wrote, reviewed or edited the manuscript before submission.

Corresponding author

Correspondence to Griet Glorieux.

Ethics declarations

Competing interests

The EUTox Work Group (of which all authors are members) receives unrestricted grants from Fresenius Medical Care, Baxter Healthcare and B. Braun Avitum AG. S.B. received honoraria for conferences from Astra-Zeneca, Amgen, Lilly and Vifor CLS. L.K. has received grants from Fresenius Kabi, Nestlé, Lallemand, AstraZeneca, and consultancy or speaker fees or travel support from AstraZeneca, Lilly, Baxter, Bayer and Fresenius Kabi.

Peer review

Peer review information

Nature Reviews Nephrology thanks the anonymous reviewers for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Glorieux, G., Burtey, S., Evenepoel, P. et al. A guide to uraemic toxicity. Nat Rev Nephrol 22, 50–68 (2026). https://doi.org/10.1038/s41581-025-01006-4

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41581-025-01006-4

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing