{
  "abstract": "Background Depression is closely linked to neuroinflammation, and in chronic kidney disease, the accumulation of uremic toxins (UTs) may promote neuroinflammatory processes through the activation of inflammatory pathways.Objective The objective of this longitudinal study was to evaluate the association between UTs and depressive symptoms in a large, well-characterised cohort of non-dialysed adults with chronic kidney disease, a population in which this relationship had not yet been investigated.Methods The Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort comprised 3033 CKD stage 2–5 patients with 5 years of follow-up. Changes over time in depressive symptoms were assessed on the Center for Epidemiologic Studies Depression (CESD) scale. Mixed models were used to examine associations between the change in the CESD score and baseline levels of the UTs phenylacetylglutamine (PAG), indoxyl sulphate (IS), indole-3-acetic acid (IAA), p-cresyl sulphate, kynurenine, kynurenic acid and trimethylamine N-oxide.Findings 2165 patients were included (median age: 68 years; mean estimated glomerular filtration rate (eGFR): 35 mL/min/1.73 m²; median baseline CESD score: 7; mean follow-up time: 4.0 years). After adjustment for confounders, the CESD score was found to have increased by 0.11 (0.04 to 0.18) points per year. A doubling in PAG level was associated with an additional increase of 0.06 (0.01 to 0.18) points per year in the CESD. A doubling in IS and IAA levels was associated with a higher mean CESD score (0.20 (0.01 to 0.39) for IS and 0.28 (0.05 to 0.50) for IAA) but not with the score’s change over time.Conclusion PAG was significantly associated with changes in CESD score over time. Higher IS and IAA levels were linked to higher mean scores. Further studies are needed to confirm these results and to determine whether lowering serum UT levels would help to manage depressive symptoms in patients with CKD.Clinical implications Further research is needed to clarify the role of UTs; a better understanding could uncover novel metabolic pathways and inform new therapeutic strategies to complement the management of depressive symptoms.",
  "authors": [
    {
      "affiliations": [
        "Ambroise Paré Hospital, University Medical Department 1, Geriatric Department, AP-HP, University Hospital Group Pais Saclay, Versailles Saint-Quentin University, Boulogne-Billancourt, France",
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Hélène Levassort"
    },
    {
      "affiliations": [
        "Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, Hauts-de-France, France",
        "MP3CV Laboratory, Jules Verne University of Picardie, Amiens, Hauts-de-France, France"
      ],
      "name": "Sophie Liabeuf"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Julie Boucquemont"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France",
        "Department of Pharmacology, Faculty of Pharmacy, Altinbas University, Istanbul, İstanbul, Turkey"
      ],
      "name": "Gaye Hafez"
    },
    {
      "affiliations": [
        "Pharmacoepidemiology Unit, Department of Clinical Pharmacology, Amiens-Picardie University Medical Center, Amiens, Hauts-de-France, France",
        "MP3CV Laboratory, Jules Verne University of Picardie, Amiens, Hauts-de-France, France"
      ],
      "name": "Solene M Laville"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Celine Lange"
    },
    {
      "affiliations": [
        "Nephrology department, University Regional Hospital, University of Lorraine, Nancy, Grand Est, France",
        "EA 4360, INSERM CIC-EC, Apemac, University of Lorraine, Nancy, Grand Est, France"
      ],
      "name": "Luc Frimat"
    },
    {
      "affiliations": [
        "Bordeaux University, INSERM, Bordeaux Public Health, U1219, CIC 1401, Bordeaux, France",
        "Centre Hospitalier d’Ardèche Méridionale, Aubenas, France"
      ],
      "name": "Christian Combe"
    },
    {
      "affiliations": [
        "Department of Nephrology and Nutrition, Hospices Civils de Lyon, Centre Hospitalier Lyon-Sud, Pierre-Bénite, France",
        "Carmen, University Claude Bernard Lyon 1, INSERM U1060, Pierre Benite, Auvergne-Rhône-Alpes, France"
      ],
      "name": "Denis Fouque"
    },
    {
      "affiliations": [
        "Carmen, University Claude Bernard Lyon 1, INSERM U1060, Pierre Benite, Auvergne-Rhône-Alpes, France"
      ],
      "name": "Maurice Laville"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France",
        "Medical and Scientific Department, Agence de la biomedecine, La Plaine Saint-Denis, France"
      ],
      "name": "Christian Jacquelinet"
    },
    {
      "affiliations": [
        "Biobanque de Picardie, Biological Resource Center of the Amiens University Hospital, Amiens, France"
      ],
      "name": "Yves-Edouard Herpe"
    },
    {
      "affiliations": [
        "Université Paris Cité, Laboratoire de Psychopathologie et Processus de Santé, Boulogne-Billancourt, France"
      ],
      "name": "Lucile Montalescot"
    },
    {
      "affiliations": [
        "Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, Garches, France",
        "UVSQ, Université Paris-Saclay, Inserm U1018, CESP, Équipe MOODS, MasSpecLab, Montigny-le-Bretonneux, France"
      ],
      "name": "Islam Amine Larabi"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Natalia Alencar de Pinho"
    },
    {
      "affiliations": [
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France",
        "AP-HP, University Hospital Group Pais Saclay, Ambroise Paré Hospital, University Medical Department 4",
        "Nephrology Department, Boulogne-Billancourt, Île-de-France, France"
      ],
      "name": "Ziad A Massy"
    },
    {
      "affiliations": [
        "Department of Pharmacology and Toxicology, Raymond Poincaré Hospital, AP-HP, Garches, France",
        "UVSQ, Université Paris-Saclay, Inserm U1018, CESP, Équipe MOODS, MasSpecLab, Montigny-le-Bretonneux, France"
      ],
      "name": "Jean-Claude Alvarez"
    },
    {
      "affiliations": [
        "Ambroise Paré Hospital, University Medical Department 1, Geriatric Department, AP-HP, University Hospital Group Pais Saclay, Versailles Saint-Quentin University, Boulogne-Billancourt, France",
        "Centre for Research in Epidemiology and Population Health (CESP), Paris-Saclay University, Inserm U1018, Versailles Saint-Quentin University, Clinical Epidemiology Team, Villejuif, France"
      ],
      "name": "Marion Pépin"
    },
    {
      "affiliations": [],
      "name": "on behalf of CKD-REIN"
    }
  ],
  "title": "Depressive symptoms in chronic kidney disease: the hidden role of uremic toxins",
  "uid": "716f0ed5-b35c-56fc-8a94-e6cc7ec99656"
}