1 This article is protected by copyright. All rights reserved.

Review article: Psychosocial factors in people with chronic kidney disease prior to renal replacement therapy1 Running title: Psychosocial factors in CKD Charlotte McKercher1 , Kristy Sanderson1 , Matthew D Jose1,2,3 1 Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia 2 Royal Hobart Hospital, Hobart, Tasmania, Australia 3 School of Medicine, University of Tasmania, Hobart, Tasmania, Australia Email addresses CM*: Charlotte.McKercher@utas.edu.au KS: Kristy.Sanderson@utas.edu.au MDJ: Matthew.Jose@utas.edu.au *Corresponding author Dr Charlotte McKercher Menzies Research Institute Tasmania Private Bag 23 Hobart TAS 7000 This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nep.12138 Accepted Article2 This article is protected by copyright. All rights reserved. Australia W: +61 3 6227 7760

F: +61 3 6227 7704 Accepted Article3 This article is protected by copyright. All rights reserved. Abstract Increasing evidence implicates psychosocial factors including depression, anxiety, perceived social support and health-related quality of life in the pathophysiology of various chronic diseases. Research examining the psychosocial aspects of kidney disease has focussed predominantly on depressive disorders in dialysis patients where they are independently associated with increased risk of mortality and poor health-related quality of life. In contrast, studies examining the influence of psychosocial factors in people with chronic kidney disease prior to the initiation of renal replacement therapy are sparse. Limited data indicate that clinical depression and depressive symptoms are common and may independently predict progression to dialysis, hospitalisation and death. In contrast, the influence of anxiety disorders, lower perceived social support and impaired health-related quality of life on the clinical course of chronic kidney disease have received little attention. Large-scale prospective cohort studies are needed to clarify the burden and prognostic impact of these factors in this vulnerable population. Given the escalating burden of chronic kidney disease worldwide examining the role of these potentially modifiable risk factors is crucial. Identifying and implementing targeted interventions in order to prevent or delay the progression of CKD and improve quality of life will be a major challenge. Accepted Article4 This article is protected by copyright. All rights reserved. Introduction Chronic kidney disease (CKD) is a global public health problem involving increased risk of cardiovascular disease (CVD) and premature death. Psychosocial explanations of health involving social, psychological and physiological processes all interact to affect the aetiology and development of CKD.1 For example, social processes such as social support may lead to psychological changes at the individual level which may influence health directly via physiological processes or modified behaviours.2

Psychosocial factors are important both because they have an impact on quality of life and have been shown to influence the progression of various chronic diseases.3 4 However, our understanding of the burden and impact of these potentially modifiable risk factors in CKD is limited. Rates of CKD are increasing in Australia with the number of patients commencing renal replacement therapy (RRT; dialysis or transplantation) between 1990-2009 escalating by 321%.5 _ENREF_5 _ENREF_62_ENREF_61_ENREF_62In addition to those being treated, around 36% of people with advanced CKD are not being dialysed6 and a similar proportion are dying via withdrawal from dialysis.7 In light of this increasing social and economic burden, examining the role of potentially modifiable non-biological risk factors on the disease trajectory of CKD should be a priority. This paper examines the prognostic role of several key psychosocial factors (depression, anxiety and perceived social support) and health-related quality of life (HRQOL) in adults with CKD (i.e. CKD stage 1-5, unless otherwise stated) prior to RRT. We explore current gaps in the literature and examine potential mechanisms through which these factors may Accepted Article5 This article is protected by copyright. All rights reserved. affect health outcomes. Potential interventions and suggestions for future research are also outlined. Depression Depression is a chronic and recurrent illness associated with substantial morbidity and allcause mortality._ENREF_9 Comorbid depressive disorders in patients with chronic disease reduce quality of life,_ENREF_20 and increase functional disability and use of healthcare services.8 Unemployment, low income, low perceived social support, and changes in familial and occupational roles are recognised risk factors for depression in people with CKD.9-12 While identifying depression in patients with kidney disease is complicated by the potential misclassification of uraemic symptoms as somatic symptoms of depression, prevalence

estimates for clinical depression in dialysis patients (CKD 5D) range from 20%-30%.13 14 _ENREF_19Similarly, around 22% of individuals with pre-dialysis CKD fulfil the criteria for major depression15 16 while 37%-55% report depressive symptoms.16-18 This is higher than the prevalence of depressive disorders in the general population (7%)9 and in those with other chronic diseases including cancer (11%).19_ENREF_20 Associations between depression and increased risk of death and hospitalisation in dialysis patients are well documented.20 13 In contrast, data for individuals with pre-dialysis CKD are sparse with few prospective cohort studies published to date (Table 1).20 Accepted Insert Table 1 here Article