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      Cognitive Impairment and Kidney Transplantation: Underestimated, Underrecognized but Clinically Relevant Problem

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          Abstract

          Background: Chronic kidney disease (CKD) affects the crosstalk between organs in the body and vast majority of studies were devoted to the interactions between the kidneys and the cardiovascular system. As of today, there is more evidence of the kidney and the central nervous system connections. Summary: Indeed, CKD and in particular dialysis therapy is linked to the increased prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment, and depression. Both traditional cardiovascular risk factors (such as diabetes, hypertension, and lipid disorders), nontraditional risk factors (such as uremic toxins, anemia, and secondary hyperparathyroidism) may predispose CKD patients to neurological disorders. Likewise, cognitive problems occur more commonly in kidney transplant recipients, regardless of age, than in the general population, but the prevalence is still understudied. Cognitive impairment is associated with a higher risk of hospitalization, mortality, decreased quality of life, or health care costs in kidney transplant recipients. Here, we review (i) the potential clinical impact of kidney transplantation on cerebrovascular and neurological complications, (ii) evaluation of patients with cognitive impairment for kidney transplantation (iii) the potential impact of cognitive impairment on waitlisted and transplanted patients on patient care, and (iv) unmet medical needs. Key Messages: Cognitive impairment in kidney transplant recipients is an underestimated, underrecognized but clinically relevant problem. The screening for cognitive declines after kidney transplantation is not yet a routine practice. Several prospective and cross-sectional studies reported improvement across some of the assessed cognitive domains after transplantation.

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          Most cited references54

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          Frailty and mortality in kidney transplant recipients.

          We have previously described strong associations between frailty, a measure of physiologic reserve initially described and validated in geriatrics, and early hospital readmission as well as delayed graft function. The goal of this study was to estimate its association with postkidney transplantation (post-KT) mortality. Frailty was prospectively measured in 537 KT recipients at the time of transplantation between November 2008 and August 2013. Cox proportional hazards models were adjusted for confounders using a novel approach to substantially improve model efficiency and generalizability in single-center studies. We precisely estimated the confounder coefficients using the large sample size of the Scientific Registry of Transplantation Recipients (n = 37 858) and introduced these into the single-center model, which then estimated the adjusted frailty coefficient. At 5 years, the survivals were 91.5%, 86.0% and 77.5% for nonfrail, intermediately frail and frail KT recipients, respectively. Frailty was independently associated with a 2.17-fold (95% CI: 1.01-4.65, p = 0.047) higher risk of death. In conclusion, regardless of age, frailty is a strong, independent risk factor for post-KT mortality, even after carefully adjusting for many confounders using a novel, efficient statistical approach.
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            Aerobic exercise and vascular cognitive impairment: A randomized controlled trial.

            To assess the efficacy of a progressive aerobic exercise training program on cognitive and everyday function among adults with mild subcortical ischemic vascular cognitive impairment (SIVCI).
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              Association between major depressive episodes in patients with chronic kidney disease and initiation of dialysis, hospitalization, or death.

              Patients with chronic kidney disease (CKD) experience increased rates of hospitalization and death. Depressive disorders are associated with morbidity and mortality. Whether depression contributes to poor outcomes in patients with CKD not receiving dialysis is unknown. To determine whether the presence of a current major depressive episode (MDE) is associated with poorer outcomes in patients with CKD. Prospective cohort study of 267 consecutively recruited outpatients with CKD (stages 2-5 and who were not receiving dialysis) at a VA medical center between May 2005 and November 2006 and followed up for 1 year. An MDE was diagnosed by blinded personnel using the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria. The primary outcome was event-free survival defined as the composite of death, dialysis initiation, or hospitalization. Secondary outcomes included each of these events assessed separately. Among 267 patients, 56 had a current MDE (21%) and 211 did not (79%). There were 127 composite events, 116 hospitalizations, 38 dialysis initiations, and 18 deaths. Events occurred more often in patients with an MDE compared with those without an MDE (61% vs 44%, respectively, P = .03). Four patients with missing dates of hospitalization were excluded from survival analyses. The mean (SD) time to the composite event was 206.5 (19.8) days (95% CI, 167.7-245.3 days) for those with an MDE compared with 273.3 (8.5) days (95% CI, 256.6-290.0 days) for those without an MDE (P = .003). The adjusted hazard ratio (HR) for the composite event for patients with an MDE was 1.86 (95% CI, 1.23-2.84). An MDE at baseline independently predicted progression to dialysis (HR, 3.51; 95% CI, 1.77-6.97) and hospitalization (HR, 1.90; 95% CI, 1.23-2.95). The presence of an MDE was associated with an increased risk of poor outcomes in CKD patients who were not receiving dialysis, independent of comorbidities and kidney disease severity.
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                Author and article information

                Journal
                KBR
                Kidney Blood Press Res
                10.1159/issn.1420-4096
                Kidney and Blood Pressure Research
                S. Karger AG
                1420-4096
                1423-0143
                2022
                July 2022
                21 April 2022
                : 47
                : 7
                : 459-466
                Affiliations
                [_a] aDepartment of Neurology, Medical University of Warsaw, Warsaw, Poland
                [_b] b1st Department of Nephrology and Transplantology, Medical University of Bialystok, Białystok, Poland
                [_c] cDepartment of Nephrology, Dialysis and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
                Author information
                https://orcid.org/0000-0002-7720-5253
                Article
                521907 Kidney Blood Press Res 2022;47:459–466
                10.1159/000521907
                35447625
                d3d0188b-61be-415e-914d-5cd90ccb724b
                © 2022 The Author(s). Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC). Usage and distribution for commercial purposes requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 22 September 2021
                : 10 January 2022
                Page count
                Tables: 1, Pages: 8
                Categories
                Review Article

                Cardiovascular Medicine,Nephrology
                Cognitive dysfunction,Immunosuppression,Kidney transplantation

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