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Cognitive performance is associated with glomerular filtration rate in patients with chronic kidney disease: results from the CKD-REIN cohort
  1. Marion Pépin1,2,
  2. Hélène Levassort1,2,3,
  3. Julie Boucquemont2,
  4. Oriane Lambert2,
  5. Natalia Alencar de Pinho2,
  6. Monica Turinici3,4,
  7. Catherine Helmer5,
  8. Marie Metzger2,
  9. Lynda Cheddani2,3,
  10. Luc Frimat6,7,
  11. Christian Combe8,9,
  12. Denis Fouque10,
  13. Maurice Laville11,
  14. Carole Ayav12,
  15. Sophie Liabeuf13,14,
  16. Christian Jacquelinet2,15,
  17. Laurent Teillet1,2,
  18. Bénédicte Stengel2,
  19. Ziad A Massy2,3
  20. On behalf of CKD-REIN Study Collaborators
    1. 1Geriatrics, APHP, UVSQ, Hopital Ambroise-Pare, Boulogne-Billancourt, France
    2. 2Clinical Epidemiology, CESP, INSERM, Paris Saclay University, Villejuif, France
    3. 3Nephrology, APHP, UVSQ, Hopital Ambroise-Pare, Boulogne-Billancourt, France
    4. 4LIRAES ED 262, Universite de Paris, Paris, France
    5. 5Bordeaux Population Health Center, INSERM U1219, Bordeaux, France
    6. 6Nephrology, Lorraine University, CHRU de Nancy, Vandoeuvre, France
    7. 7EA 4360, Lorraine University, INSERM CIC-EC, Apemac, France
    8. 8Nephrology, Bordeaux University Hospital, Bordeaux, France
    9. 9Biotis, INSERM U1026, Bordeaux, France
    10. 10Nephrology, Claude Bernard Lyon 1 University, Centre Hospitalier Lyon-Sud, Pierre-Benite, France
    11. 11Carmen, INSERM U1060, University Claude Bernard Lyon 1, Pierre Benite, France
    12. 12Clinical Epidemiology, INSERM, Lorraine University, CHRU de Nancy, Nancy, France
    13. 13Pharmacology, Amiens University, Amiens, France
    14. 14MP3CV Laboratory EA7517, Université de Picardie Jules Verne, Amiens, France
    15. 15Medical and Scientific Departement, Agence de la Biomedecine, La Plaine Saint-Denis, France
    1. Correspondence to Dr Marion Pépin, Geriatrics, APHP, UVSQ, Hopital Ambroise-Pare, Boulogne-Billancourt 92100, France; marion.pepin{at}


    Background Chronic kidney disease (CKD) is associated with cognitive impairment in general population. We assessed the association between kidney and cognitive functions in patients with CKD and the influence of cardiovascular (CV) risk factors, and depression on this association.

    Methods The CKD-Renal Epidemiology and Information Network cohort included 3033 patients with CKD stages 3–4, followed for 5 years. Cognitive function was assessed with the Mini-Mental State Examination (MMSE) and estimated glomerular filtration rate (eGFR) with the CKD-Epidemiology Collaboration equation-creatinin formula. Evolution of the MMSE score over time and its association with baseline eGFR were investigated with linear mixed models. We assessed the risk of incident cognitive outcome (hospitalisation or death with relevant International Classification of Disease-10 codes), with a Cox proportional hazard model.

    Results The mean age was 66.8, the mean eGFR was 33 mL/min/1.73 m2 and 387 patients (13.0%) had an MMSE score below 24 at baseline. A 10 mL/min/1.73 m2 decrement of baseline eGFR was associated with a mean MMSE decrease of 0.12 (95% CI 0.04 to 0.19) after adjustment for demographic characteristics, depression, CV risk factors and disease; but baseline eGFR was not associated with MMSE temporal evolution. HR for cognitive outcome during follow-up (median 2.01 years) associated with a 10 mL/min/1.73 m2 decrement of baseline eGFR was 1.35 (1.07, 1.70) (p=0.01) after adjustment.

    Conclusions In patients with CKD, lower eGFR was associated with worse cognitive performance and incident cognitive events, independently of demographics, CV risk factors and depression.

    Trial registration number NCT03381950.

    • cognition
    • epidemiology
    • renal medicine

    Data availability statement

    Data are available on reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available, due to privacy or ethical restrictions.

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    Data availability statement

    Data are available on reasonable request. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available, due to privacy or ethical restrictions.

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    • Collaborators The CKD-REIN Study Collaborators include members of the steering committee and coordinating centre, and site investigators.Steering committee and study coordination: Natalia Alencar de Pinho, Carole Ayav, Christian Combe, Denis Fouque, Luc Frimat, Christian Jacquelinet, Maurice Laville, Sophie Liabeuf, Ziad A Massy, Christophe Pascal, Bruce M Robinson, Roberto Pecoits-Filho, Bénédicte Stengel, Céline Lange, Marie Metzger, Elodie Speyer.CKD-REIN site investigators: Alsace : Prs T. Hannedouche and B. Moulin (CHU, Strasbourg), Dr A. Klein (CH Colmar) Aquitaine : Pr C. Combe (CHU, Bordeaux), Dr J.P. Bourdenx (Clinique St Augustin, Bordeaux), Dr A. Keller, Dr C. Delclaux (CH, Libourne), Dr B. Vendrely (Clinique St Martin, Pessac), Dr B. Deroure (Clinique Delay, Bayonne), Dr A. Lacraz (CH, Bayonne) Basse Normandie : Dr T. Lobbedez (CHU, Caen), Dr I. Landru (CH, Lisieux) Ile de France : Pr Z. Massy (CHU, Boulogne – Billancourt), Pr P. Lang (CHU, Créteil), Dr X. Belenfant (CH, Montreuil), Pr E. Thervet (CHU, Paris), Dr P. Urena (Clinique du Landy, St Ouen), Dr M. Delahousse (Hôpital Foch, Suresnes) Languedoc – Roussillon : Dr C. Vela (CH, Perpignan) Limousin : Pr M. Essig, Dr D. Clément (CHU, Limoges) Lorraine : Dr H. Sekhri, Dr M. Smati (CH, Epinal) Dr M. Jamali, Dr B. Hacq (Clinique Louis Pasteur, Essey-les-Nancy), Dr V. Panescu, Dr M. Bellou (Polyclinique de Gentilly, Nancy), Pr Luc Frimat (CHU, Vandœuvre-les-Nancy) Midi-Pyrénées : Pr N Kamar (CHU, Toulouse) Nord-Pas-de-Calais : Prs C. Noël et F. Glowacki (CHU, Lille), Dr N. Maisonneuve (CH, Valenciennes), Dr R. Azar (CH, Dunkerque), Dr M. Hoffmann (Hôpital privé La Louvière, Lille) Pays-de-la Loire : Pr M. Hourmant (CHU, Nantes), Dr A. Testa (Centre de dialyse, Rezé), Dr D. Besnier (CH, St Nazaire) Picardie : Pr G. Choukroun (CHU, Amiens), Dr G. Lambrey (CH, Beauvais) Provence-Alpes - Côte d’Azur : Pr S. Burtey (CHU, Marseille), Dr G. Lebrun (CH, Aix-en-Provence), Dr E. Magnant (Polyclinique du Parc Rambot, Aix-en-Provence) Rhône-Alpes : Pr M. Laville, Pr D. Fouque (CHU, Lyon-Sud) et L. Juillard (CHU Edouard Herriot, Lyon), Dr C. Chazot (Centre de rein artificiel Tassin Charcot, Ste Foy-les-Lyon), Pr P. Zaoui (CHU, Grenoble), Dr F. Kuentz (Centre de santé rénale, Grenoble).

    • Contributors MP, as guarantor, takes full responsibility for the data, the analyses and interpretation, and the conduct of the research. MP has full access to all of the data and has the right to publish any and all data separate apart from any sponsor. All authors meet the criteria for authorship stated in the ICMJE Criteria for Authorship. All authors revised and approved the final version of the paper and agree with all the aspects of the manuscript. We have no conflicts of interest to disclose. Each named author has substantially contributed to the manuscript. Regarding the authors’ contributions, MP, HL, JB and ZAM designed the present study, and CC, LF, ML, CJ, DF, SL, ZAM and BS designed the CKD-REIN cohort; CC, DF, LF, CJ, ML, ZAM, LC, CA, BS organised data collection; MP, HL, JB, MT, LC, OL, NAdP and MM provided statistical analysis; MP and HL drafted and edited the manuscript; MP, JB, MT, HL, BS, ZAM conducted the study and reviewed the plan; JB, CC, DF, LF, CJ, SL, ML, ZAM, LC, CA, BS, CH, LT contributed to the discussion and critically reviewed the manuscript. MP and HL contributed equally to this manuscript.

    • Funding CKD-REIN is funded by the Agence Nationale de la Recherche through the 2010 «Cohortes-Investissements d’Avenir » program (ANR-IA-COH-2012/3731) and by the 2010 national Programme Hospitalier de Recherche Clinique. CKD-REIN is also supported through a public-private partnership with Fresenius Medical Care and GlaxoSmithKline (GSK) since 2012 and Vifor France since 2018, Sanofi-Genzyme from 2012 to 2015, Baxter and Merck Sharp & Dohme-Chibret (MSD France) from 2012 to 2017, Amgen from 2012 to 2020, Lilly France from 2013 to 2018, Otsuka Pharmaceutical from 2015 to 2020, and AstraZeneca from 2018 to 2021. Inserm Transfert set up and has managed this partnership since 2011. CKD-REIN is currently funded by a public-private partnership with four pharmaceutical companies (AstraZeneca, Fresenius Medical Care, GSK, and Vifor France); this funding is not related to the content of the present manuscript.

    • Competing interests BS reports grants for the CKD-REIN cohort study from Amgen, AstraZeneca, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp and Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka, and Vifor France. ZAM reports grants for CKD-REIN and other research projects from Amgen, Baxter, Fresenius Medical Care, GlaxoSmithKline, Merck Sharp and Dohme-Chibret, Sanofi-Genzyme, Lilly, Otsuka and the French government, as well as fees and grants to charities from Astellas, Baxter, Daichii and Sanofi-Genzyme; these sources of funding are not necessarily related to the content of the present manuscript. DF reports grants for other research projects from Fresenius Kabi and Sanofi.The other authors declare that they have no competing interests.

    • Provenance and peer review Not commissioned; externally peer reviewed.

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