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Clinical implications of geriatric impairments in chronic kidney disease kidney in chronic impairments of geriatric implications Clinical Namiko A. Namiko Goto Clinical implications of geriatric impairments in chronic kidney disease: Frailty, falls, fractures, and functional decline Namiko A. Goto Clinical implications of geriatric impairments in chronic kidney disease: Frailty, falls, fractures and functional decline Namiko A. Goto Financial support by the Dutch Kidney Foundation. Cover design and layout: © evelienjagtman.com Printed by: Ridderprint BV www.ridderprint.nl ISBN: 978-94-6375-456-9 © 2019 Namiko Goto All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage or retrieved system, without permission in writing from the author. Clinical implications of geriatric impairments in chronic kidney disease: Frailty, falls, fractures and functional decline Klinische implicaties van geriatrische problemen bij patiënten met chronische nierinsufficiëntie Kwetsbaarheid, vallen, fracturen en functionele achteruitgang (met een samenvatting in het Nederlands) Proefschrift ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag van de rector magnificus, prof.dr. H.R.B.M. Kummeling, ingevolge het besluit van het college voor promoties in het openbaar te verdedigen op dinsdag 19 november 2019 des middags te 4.15 uur door Namiko Anna Goto geboren op 30 september 1988 te Noordwijk Promotoren: Prof. dr. M.C. Verhaar Prof. dr. M.H. Emmelot-Vonk Copromotoren: Dr. M.E. Hamaker Dr. H.C. Willems Table of contents Chapter 1 General introduction and outline of the thesis 7 Part 1 Frailty Chapter 2 Geriatric assessment in patients with end-stage kidney 21 disease Chapter 3 Frailty screening tools for elderly patients incident to dialysis 49 Chapter 4 Geriatric assessment and the relation with mortality and 75 hospitalizations in older patients starting dialysis Part 2 Falls & Fractures Chapter 5 The association between chronic kidney disease, falls and 97 fractures: a systematic review Chapter 6 Accidental falling in community dwelling elderly with 131 chronic kidney disease Chapter 7 Thoracic vertebral fractures and hyperkyphosis in elderly 155 patients with end-stage kidney disease; do these patients have different clinical outcomes? Chapter 8 The prevalence and incidence of vertebral fractures in end- 177 stage kidney disease and the role of parathyroid hormone Part 3 Functional outcome, quality of life and caregiver burden Chapter 9 Association of initiation of maintenance dialysis with 213 functional status and caregiver burden Chapter 10 Quality of life after the initiation of dialysis or maximal 235 conservative management in elderly patients Part 4 Clinical implications of geriatric impairments in chronic kidney disease Chapter 11 Geriatric considerations in elderly patients with end-stage 257 kidney disease Chapter 12 General discussion and conclusions 273 Addendum Summary 291 Nederlandse samenvatting 297 List of authors with affiliations 305 Acknowledgments 309 Dankwoord 311 List of publications 317 Curriculum Vitae 321 Chapter 1 General introduction and outline of the thesis General introduction 01 General introduction The general population is aging rapidly; at this moment approximately 8% of the population in the Netherlands is older than 75 years and it is estimated to increase to almost 15% in 2040.1 As patients age, illnesses such as chronic kidney disease become more prevalent.2 Several studies estimated that between 23% and 36% of patients 65 years and older have chronic kidney disease.3 The Kidney Disease Improving Global Outcomes (KDIGO) workgroup defines chronic kidney disease as “abnormalities of kidney structure or function, present for more than 3 months, with implications for health”.4 Although chronic kidney disease in early stages is mostly asymptomatic, it can eventually lead to a broad range of complications that affect multiple organ systems. Important sequelae are anemia, chronic inflammation, abnormalities in calcium, phosphorus and mineral-regulating hormones, and abnormalities in sodium, potassium, water and acid- base homeostasis.5 Only part of patients with chronic kidney disease will eventually progress to end-stage kidney disease (ESKD).6 This is a state where the accumulation of toxins, fluid, and electrolytes lead to the uremic syndrome and if not treated, eventually death. While kidney dysfunction progresses to ESKD, patients can develop a wide range of symptoms, such as fatigue, pruritus, anorexia, and symptoms of fluid overload.7 To treat these symptoms, to maintain quality of life and to prolong life, there are several options for renal replacement therapy (RRT): hemodialysis (in center or at home), peritoneal dialysis and kidney transplantation. Although kidney transplantation is certainly an option, due to shortage of transplants and health requirements, by far most elderly will start dialysis therapy8 and remain on this therapy for the rest of their life. Both hemodialysis and peritoneal dialysis are very intensive treatments with high therapy burden.9 Besides RRT, patients can also choose for maximal conservative management, which is dedicated to symptom management to maintain quality of life as much as possible. Previous retrospective studies showed that dialysis treatment in patients of 80 years and older did not offer survival benefit over maximal conservative management.10–12 A similar lack of survival benefit was seen for the comorbid patients of 75 years and older.11 Given the burden of dialysis therapy, this raises questions if dialysis is the best treatment for elderly patients with ESKD. However, some elderly patients do benefit, and age itself does not seem a good indicator of lack of benefit, as biological age can differ significantly from calendar age. The elderly population is very heterogeneous, with high variability in comorbidity burden, medication use and presence of geriatric impairments. In various study populations, awareness of the presence of geriatric impairments improved outcome 9 Chapter 1 by adjusting treatment decisions and creating a personalized treatment plan for the elderly patient.13–15 Therefore, more knowledge on specific geriatric impairments, such as frailty, falls, fractures and functional status, and their relation with outcome may help to better select patients who may benefit from dialysis treatment. In addition, it is not life prolongation that elderly value most: most elderly with advanced chronic kidney disease prioritize maintaining independence over life prolongation.13 Subsequently, more information on the course of functional status could potentially help patients, caregivers and healthcare providers in their discussion whether to start dialysis. Frailty A frequently used concept to identify patients with high risk of poor health outcomes is frailty. This can be defined as “a biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, thereby causing vulnerability to adverse outcomes”.17 Consequently, frail patients have a decreased ability to cope with daily or acute stressors. This can be illustrated by the following example: in non-frail patients a mild urinary tract infection frequently presents with dysuria. In very frail patients, this mild urinary tract infection can have a disproportionate effect, leading to a delirium, accidental fall or increased functional dependency. In non-ESKD study populations, frail patients were at higher risk of mortality, hospitalizations, falls and functional decline.13,18,19 Therefore, the assessment of frailty could provide an opportunity to improve decision-making in elderly patients with end-stage kidney disease. The geriatric assessment is the most accepted method to diagnose frailty.20,21 This is a systematic method that uses the domains somatic, psychologic, physical function and social activity/support to assess the health status of patients. In various study populations, the use of a geriatric assessment led to an improved survival, independence, treatment tolerance and treatment completion.13–15,18 Therefore, by distinguishing frail from fit patients, this method could potentially help to select patients that are likely to benefit from dialysis treatment and on the other hand select patients in whom maximal conservative management might be a more appropriate option. One important disadvantage of the geriatric assessment is that it is time-consuming; a full geriatric assessment takes approximately one hour. As the ESKD population is aging, not every clinic may have enough time to perform a complete geriatric assessment in every elderly patient. A possible solution could be the use of a frailty screening tool to select patients that are likely to benefit from the geriatric assessment, provided that the frailty screening tool is sensitive enough. 10 General introduction 01 Falls & Fractures Falls are a major health issue in the elderly population. The World Health organization defined a fall as “an event which results in a person coming to rest inadvertently on the ground or floor or other lower level, excluding intentional change in position to rest in furniture, wall or other objects”.22 Previous research estimated that approximately a third of people aged 65 years and older fall each year.23 This rate is even higher in the institutionalized elderly.24 Falls can lead