FormalPara Key Summary Points

Patients with late-stage chronic kidney disease (CKD) who are not receiving dialysis but who have physical functioning limitations experience a range of impacts that affect their daily lives.

In this study, patients were interviewed about their physical functioning, and their responses were used to develop a comprehensive conceptual model of physical functioning limitations experienced by patients with late-stage CKD.

Patients primarily reported physical functioning limitations associated with walking, and behavioural impacts related to needing more rest and participating in fewer activities.

The development of a comprehensive conceptual model summarizing how reported symptoms and impacts associated with physical functioning limitations can relate to one another provides a holistic view of the patients’ experiences.

Digital Features

This article is published with digital features, including an infographic, to facilitate understanding of the article. To view digital features for this article, go to https://doi.org/10.6084/m9.figshare.25444681.

Introduction

Chronic kidney disease (CKD) refers to abnormalities in the structure or function of the kidney present for more than 3 months and with implications for health [1, 2]. CKD is an increasingly prevalent cause of death worldwide, moving from the 17th to the 12th leading cause of death globally between 1990 and 2017, and is expected to be the fifth leading cause of death worldwide by 2040 [3, 4]. CKD has five progressive stages, defined by estimated glomerular filtration rate (eGFR). Patients with late-stage CKD (stages IV–V) have an eGFR of less than 30 mL/min/1.73 m2 [1, 2]. Polycystic kidney disease (PKD) is a form of CKD in which multiple fluid-filled cysts grow; these can enlarge and cause damage to the kidneys [5].

Reduced physical functioning is one of the most frequently reported impacts associated with CKD in published literature [6] and has been associated with poorer outcomes in patients with CKD [7]. Physical functioning is recognized as the ability of an individual to carry out activities that require physical capability; these may range from basic self-care to more intense activities [8]. Physical inactivity in patients with CKD is associated with worse health-related quality of life (HRQoL) and increased mortality [9, 10]; consequently, it is an important aspect of the total patient experience. Preventing the decline of kidney function through therapeutic intervention could result in health benefits for patients from preservation of physical functioning and maintenance of physical activity. Previous studies have reported patient perceptions of physical functioning in patients with CKD, often with a focus on its impacts on exercise [11,12,13]. However, there is currently limited information available regarding patient perceptions of the impact of CKD on day-to-day physical activity and functioning for individuals with late-stage CKD who are not receiving dialysis, or on how concepts reported by patients may relate to one another. Physical functioning limitations are likely to affect various aspects of patients’ lives—patients may have reduced physical functioning due to challenging symptoms or they may consciously reduce their physical functioning by avoiding activities they find challenging. Having a more complete awareness of how patients are affected can help identification of which aspects of a condition are important to patients so that appropriate assessments and tools may be used to record the impact of a disease or effectiveness of therapies.

Clinical outcome assessments (COAs) are used in clinical practice and clinical trials to capture how patients feel, function or survive and can help develop an understanding of whether therapies are clinically beneficial [14,15,16,17]. Qualitative interviews with patients provide data about what experiences they have; reporting of disease-relevant concepts (e.g. symptoms and changes in behaviours, emotions and social interactions) and can inform the selection, development, or modification of COA measures used to quantify those experiences [18, 19]. Digital tools may quantify levels of patient physical functioning either passively (using sensors, such as activity monitors, to track patient activity) or actively (having patients perform set tasks); however, they cannot capture the reasons for their findings. COAs may record purposeful changes in patient behaviour or activities due to experiences associated with their condition; for example, symptoms such as shortness of breath may cause patients to avoid going on walks. Consequently, combining digital tools with COAs enables a more holistic assessment of the patient experience. Such assessments may then be used in clinical research and support the development of more effective therapies.

Patients with later stages of CKD typically experience greater reductions in physical functioning than patients with earlier stages [20, 21]. Consequently, they are of particular interest when identifying the types of physical functions impacted by CKD and how patients are affected by these limitations. The aim of this study was to explore and document experiences associated with physical functioning limitations for patients with late-stage CKD who are not on dialysis. Concept elicitation interview methods [22] were used to investigate concepts associated with physical functioning limitations that are relevant and important to patients, including changes in behaviour and physical activity. The study also aimed to use the patient responses to develop a comprehensive conceptual model which provides a holistic description of the experiences of patients with late-stage CKD who have physical functioning limitations. Findings from this study can help to develop new ways of measuring physical functioning in patients with CKD by combining COAs and digital tools.

Methods

Study Design Overview

A previously published targeted literature review (TLR) that focused on patients with CKD stages IV–V, and previous interviews with patients diagnosed with CKD stages IIIa–IIIb [7, 23] were used to generate a preliminary conceptual model summarizing concepts relevant to physical functioning limitations in patients with CKD. This informed the design of an interview guide to be used for qualitative concept elicitation interviews which were conducted with patients with late-stage CKD (stages IV–V). Key concepts related to physical functioning limitations associated with CKD were identified using the patients’ responses. This information was used to develop a comprehensive conceptual model on physical functioning limitations in patients with late-stage CKD. An overview of the study design is given in Fig. 1. Patients receiving dialysis and/or with comorbidities, such as type 2 diabetes, were expected to represent a distinct population who potentially face additional experiences which affect physical functioning (e.g. frequency of hospital visits, frequency/duration of treatment, and symptoms related to their condition/treatment) compared with patients not receiving dialysis or without such comorbidities [24]. Excluding those individuals from this study meant that, to the greatest extent possible, physical functioning experiences recorded were associated only with CKD. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and is consistent with Good Clinical Practice and the regulations of the US Food and Drug Administration (Fig. 1).

Fig. 1
figure 1

Study flow diagram. CKD chronic kidney disease

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Targeted Literature Review

A TLR was performed to identify concepts related to physical functioning limitations in adults with CKD stages IV–V. The TLR in this study expanded upon a previously published TLR which included searches for articles published between October 2010 and November 2019 [7]. The previous TLR used the databases PubMed, Embase and Cochrane to identify relevant articles and used congress and clinical associations websites to search for relevant abstracts. For this study, PubMed was used to search for additional articles published between November 2019 and December 2020 and the same congresses and clinical associations were searched for abstracts as in the previous TLR. Both TLRs were limited to English language publications and had the same searches performed and exclusion criteria applied [7].

Preliminary Conceptual Model

A preliminary conceptual model on physical functioning limitations in patients with CKD was generated using concepts identified from the TLRs focused on patients with CKD stages IV–V and previous interviews with patients with CKD stages IIIa–IIIb [7, 23]. The concepts were grouped into six categories based on the World Health Organization (WHO)-approved International Classification of Functioning disability and health (also known as ICF) model [25]. These categories were body function and structure impairment (signs and symptoms; concepts related to impacts that affect the body’s ability to function normally or considered a structural impairment), physical activity limitations (concepts that limited the patient’s ability to perform physical actions, movements or activities), participation restrictions (concepts that restricted the patients’ ability to participate in activities), impact on sleep (concepts related to changes or impacts on sleep), environmental factors (concepts not within the patient’s control e.g. family, work, government agencies, laws, and cultural beliefs) and personal factors (concepts associated with differences between patients independent of their health condition e.g. race, sex, age).

Patient Recruitment

The agency Global Perspectives assisted in recruiting patients. Recruitment took place via email, social media or physician contact between 25 March and 8 September 2021. Patients completed an informed consent form online, after which they answered several screening questions over the phone to confirm eligibility. Patients were eligible for this study if they were English-speaking, over 18 years old, residing in the USA (excluding Puerto Rico), diagnosed with CKD stage IV or V, not receiving dialysis and had access to a telephone or an internet-connected computer. Patients were excluded if they had been diagnosed with class III/IV heart failure, pulmonary diseases, type 2 diabetes, cancer, mental illness, or musculoskeletal diseases. Eligible patients were requested to provide confirmation of their CKD diagnosis and staging, either through signed documentation from their physicians or alternative forms of evidence such as recent documentation discussing their medical history. There was difficulty recruiting patients because the majority of the identified potential patients with CKD stage V were receiving dialysis; consequently, the patient eligibility criteria were adapted so that patients with PKD, a form of CKD, could also participate. However, this study limited recruitment of patients with PKD to a third of the total number of recruited patients. A summary of the patient eligibility criteria is given in Supplementary Materials Table S1. Patients received compensation for their time following completion of the interview process.

Concept Elicitation Interviews

The concept elicitation interviews were conducted by one interviewer (Joshua Maher, PhD, Male, Consultant, IQVIA) who was trained in conducting concept elicitation interviews. Patients had no relationship with and knew no personal characteristics about the interviewer. Patients were informed that the findings from their interviews may contribute to a better understanding of how CKD can impact physical activity in daily life for patients. The preliminary conceptual model informed the design of a semi-structured interview guide which was used to help capture key concepts related to how patients with CKD stages IV–V experience physical functioning limitations, including behavioural and activity participation restrictions. The interviews were not designed to identify CKD symptoms and impacts beyond those associated with physical functioning limitations. Before use, the interview guide was approved by the Western Institutional Review Board (WIRB)–Copernicus Group Institutional Review Board for ethics compliance. The interviews were conducted in accordance with the recommended guidelines provided by the International Society for Pharmacoeconomics and Outcomes Research Good Research Practices Task Force [26] and reflect the US Food and Drug Administration guidance on methods to identify what is important to patients [18].

Patient interviews took place between 6 April and 14 September 2021. The interviews lasted approximately 60 min and were performed one-to-one over the telephone or audio call (WebEx); with the patients’ permission, the interviews were audio recorded. The interviewer followed the semi-structured interview guide and asked open-ended questions so that patients could report concepts either ‘spontaneously’ or following prompting (‘probed’). Repeat interviews were not conducted and transcripts were not returned to participants for their feedback.

Additionally, patients were asked to rate the overall impact of their physical limitations on their daily life using a scale of 0–10 (0 being ‘not impacted at all’ and 10 being ‘extremely impacted’) to understand how severely patients perceive themselves to be impacted by physical limitation. Patients were also asked which symptoms they would most want a new treatment to improve and how they would expect their physical functioning to improve if their symptoms were alleviated through a new treatment; this was to understand which symptoms patients perceive to be most urgent to address and what type of activities they would want a new treatment to improve.

Data Analysis

The audio recordings from the patient interviews were transcribed verbatim to produce transcript documents which were then anonymized for coding analysis. The interview transcripts were coded by Joshua Maher and Vrishali Radke (IQVIA). Coding was performed in the order in which the interviews were conducted using the qualitative research software ATLAS.ti (version 8; ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). Pre-defined codes were used which were based on concepts identified in the preliminary conceptual model and coding rules that were established before coding began. After an inter-coder agreement score of over 0.7 was achieved between double-coded transcripts (based on the pre-defined Krippendorff’s c-alpha binary > 0.7 [26]); the remaining transcripts were divided between and coded by the two coders independently. Concepts were only recorded if they contributed to, or were discussed in relation to, physical functioning limitations. Physical functioning limitations were defined as immediate limitations to movement that a patient experienced, such as walking, standing, and lifting. Only symptoms reported by patients that contribute to physical limitations (e.g. fatigue, oedema/swelling, shortness of breath, pain) were recorded. The recorded concepts were also labelled as either ‘probed’ or ‘spontaneous’. Concepts were initially grouped into six categories based on the preliminary conceptual model: body function and structure impairment (signs and symptoms), physical activity limitations, participation restrictions, impact on sleep, environmental factors and personal factors. Concepts and their categories were reconfigured when more appropriate grou**s were identified; multiple rounds of review were carried out to ensure that the new grou**s were representative of the patient experience. Additional coding was performed to identify connections between concept groups. Achievement of concept saturation was used to confirm when a suitable number of patients had been interviewed. Saturation was defined as the point at which additional patient interviews did not contribute new unique concepts [27]. To evaluate when saturation of concepts occurred in this study, prior to coding, the transcripts were grouped chronologically into waves containing up to five interview transcripts. This study focused on saturation of physical functioning limitations concepts owing to the interviews not being designed to identify concepts beyond those related to physical functioning.

Updated Conceptual Model

A comprehensive conceptual model was developed which summarized concepts associated with physical functioning limitations in patients with CKD stage IV–V. This conceptual model was based on the ICF classifications [25] and developed upon the preliminary conceptual model using the concepts identified from the patient interviews.

Results

Targeted Literature Review

A total of 118 publications (100 from 2010–2019 [7], 18 from 2019–2020) were identified for potential inclusion in this study. Following article screening, nine publications were identified as relevant to understanding physical functioning limitations in patients with late-stage CKD. In the earlier interview study of patients with CKD stages IIIa–IIIb [23], 17 interviews (out of 22) were considered to report impacts associated with physical functioning viewed by patients as be related to CKD. From the TLR and previous interview study, 14 concepts were deemed relevant to physical functioning limitations in patients with CKD. Tiredness/lack of energy/lack of strength/feeling weak, generalized oedema/swelling and muscle weakness/cramps were identified as the most frequently reported concepts (Supplementary Materials Table S2). Using concepts identified through the TLR and previous interview study [7, 23], a preliminary conceptual model was developed summarizing the relationship between late-stage CKD and patient physical functioning limitations (Supplementary Materials Fig. S1).

Patient Demographics

A total of 82 patients with CKD were contacted to participate in the study, however, only 25 met the requirements, including eligibility criteria, to participate. The interviewed patients had CKD stage IV (n = 19) or V (n = 6), and of those individuals, eight had PKD (CKD stage IV, n = 7; CKD stage V, n = 1). While efforts were made to recruit a diverse sample of patients, the mean age of participants was 57 years (range, 40–74), most patients were women (n = 19) and most patients were white (n = 20). Patient demographics are summarized in Table 1.

Table 1 Patient demographics
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Concept Elicitation Interviews

The data are mostly presented by combining results for patients with CKD stages IV and V, collectively referred to as patients with ‘late-stage’ CKD. Sub-analyses by disease stage were not conducted because of the low number of patients with CKD stage V.

Twenty-three (92%) of the interviewed patients reported concepts related to physical functioning limitations associated with late-stage CKD. The two patients who reported no impact on physical functioning both had CKD stage IV (female, n = 1; male, n = 1). One of these patients reported: “I’m aware of my kidney disease, so I think about it. And maybe mentally it affects what I might be doing, but not to any great degree” which suggests they may be limiting themselves from performing physical activities. All subsequent reported data are based only on the 23 patients who reported physical limitations.

The categories for grou** concepts were updated on the basis of the types of concepts reported by patients. Concepts were grouped into one of six broad categories: physical functioning limitations/difficulties, behavioural impacts, activity participation restrictions, symptoms attributed to physical functioning limitations, impacts on sleep and emotional functioning impacts related to physical functioning limitations. Summaries of the reported concepts can be found in Supplementary Materials Tables S3 and S4, and a selection of patient quotes for the most frequently reported concepts from each category are listed in Table 2.

Table 2 Patient quotes representing the most frequently reported concepts
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Physical Functioning Limitations/Difficulties

A total of 13 concepts related to physical functioning limitations/difficulties were reported. Saturation of concepts related to physical functioning limitations was achieved by wave 2 of the interviews, indicating a suitable sample size had been reached. Most concepts (n = 9, 69%) were reported during the first wave and the remaining concepts (n = 4, 31%) were reported in wave 2. Most references to concepts (79%) were spontaneous. The reported physical functioning limitations/difficulties were broadly organized into six groups: walking limitations, walking up and down stairs, prolonged physical function, core body movement limitation, difficulty with balance (which patients considered as being due to oedema/swelling) and lifting arms above head. The most frequently reported concept was walking up and down stairs (n = 19, 83%). Twenty-one patients (91%) also reported walking limitations of some form (distance [n = 17, 74%], speed [n = 16, 70%], inability to walk [n = 6, 26%], incline [n = 5, 22%] or duration [n = 4, 17%]).

Behavioural Impacts

A total of 18 concepts attributed to behavioural impacts associated with patients’ physical functioning limitations were reported. All 23 patients reported the need for rest/subsequent periods of rest. Other frequently reported concepts were participation in fewer activities (n = 21, 91%), reducing frequency of activities (n = 15, 65%), modifying plans for an activity (n = 15, 65%) and reducing the pace of activities (n = 13, 57%). In addition, 15 patients (65%) reported avoiding activities all together (lifting heavy items [n = 13, 57%], day-to-day activities such as walking up the stairs [n = 7, 30%] and walking places [n = 9, 39%]).

Activity Participation Restrictions

A total of 14 activity participation restrictions attributed to patients’ physical functioning limitations were reported. Twenty-two patients reported that their physical functioning limitations have an impact on instrumental activities of daily living, including reduced ability to handle household tasks (n = 22, 96%) and difficulty shop** (n = 13, 57%). Other frequently reported impacts related to activity participation were reductions in social activities/social life (n = 18, 78%), sports/leisure activities (n = 17, 74%), job/work routine efficiency (n = 16, 70%) and ability to perform exercise (n = 16, 70%).

Symptoms

A total of seven symptoms attributed to patients’ physical functioning limitations were reported. Symptoms related to physical functioning limitations were reported by all 23 patients. All patients reported lack of energy/tiredness/fatigue. Patients also frequently reported muscular difficulties/lack of strength (n = 19, 83%), pain (such as in the abdomen, back and limbs; n = 16, 70%) and shortness of breath (n = 16, 70%).

Impacts on Sleep

A total of three impacts on sleep attributed to patients’ physical functioning limitations were reported. Approximately three-quarters of the patients (n = 18, 78%) reported that their sleep was impacted. Patients reported experiencing poor/reduced quality of sleep (n = 15, 65%), difficulty falling asleep (n = 8, 35%) and waking up during the night (n = 6, 26%). Of the six patients who reported waking up during the night, five reported it as being due to the need to urinate.

Emotional Functioning Impacts

A total of four emotional functioning impacts attributed to patients’ physical functioning limitations were reported. Eleven patients reported emotional responses which resulted from the physical limitations of late-stage CKD. Four emotional functioning impacts were reported: frustration (n = 8, 35%), embarrassment (n = 5, 22%), feeling depressed (n = 3, 13%) and feeling like a burden on family members (n = 3, 13%).

Average Impact of Physical Limitations on Patients’ Lives

Twenty-two patients rated their perceived overall impact of their physical limitations on daily life, giving an average impact rating of 5.4/10 (Supplementary Materials Fig. S2). Fifteen patients (68%) gave an impact rating of at least five and one patient (5%) reported no impact at all.

Comprehensive Conceptual Model

The preliminary conceptual model was updated to develop a more comprehensive version summarizing experiences of the interviewed patients with late-stage CKD and physical functioning limitations (Fig. 2). Of the 90 concepts included, five were carried over from the preliminary conceptual model, 21 were revised from the preliminary conceptual model to align more closely with the patients’ interview responses, and 64 were added on the basis of the responses in this study’s patient interviews.

Fig. 2
figure 2

Conceptual model summarizing the experience of patients with late-stage CKD who have physical functioning limitations. Blue diamonds indicate concepts identified only during the patient interviews; orange circles indicate concepts from the preliminary conceptual model that were updated to reflect patient interview responses. Concepts without a circle were identified during the TLR or previous patient interviews [7, 23]. Symptoms that were deemed closely related to physical functioning limitations are in green. aDefined as sports carried out primarily for pleasure. bDefined as exercise carried out primarily for health. CKD chronic kidney disease, PKD polycystic kidney disease, TLR targeted literature review

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This comprehensive conceptual model presents common associations between concepts, as well as directionality of these connections, identified through patient responses. The majority of concepts have unidirectional relationships: for example, symptoms (e.g. muscular difficulties/lack of strength) can cause physical functioning limitations (e.g. walking limitations) which then result in behavioural impacts (e.g. reduced levels of activity) and/or restrictions in activity participation (e.g. impacts on instrumental activities of daily living). In some cases, it was difficult to identify which concepts were the causes and which were the effects, owing to them being closely interlinked; this primarily occurred between concepts reported as ‘symptoms’ and ‘physical functioning limitations’. For example, out of 21 patients who reported a form of difficulty while walking (physical functioning limitation), 18 reported that it was caused by lack of energy/tiredness/fatigue (symptom) (“I feel weaker, not as energetic. I seem to have a harder time just doing things like walking maybe 100 yards, but not that I don’t do it. I walk at a slower rate now…. It’s kind of a combination of exhaustion and just feeling weak”), whereas nine out of 19 patients who reported difficulty walking up and down stairs (physical functioning limitation) said this was due to lack of energy/tiredness/fatigue or shortness of breath (symptoms) (“I just get out of breath easily, so I just stop…. I’ll just maybe go up a flight, stop and do a deep breath. Go up another flight and catch another breath. And then make the final flight”). Overall, the comprehensive conceptual model presents how reported concepts related to physical functioning limitations went on to impact other aspects of patients’ lives (Fig. 2).

Treatment Expectation

Seventeen patients reported the symptoms which they would most want a new treatment for late-stage CKD to improve, and 16 patients reported how they would expect their physical functioning to improve if their symptoms were alleviated through a new treatment. Patients reported that they believed alleviation of fatigue would have the largest effect on their physical functioning (n = 10, 59%; Supplementary Materials Table S5). Additionally, they would expect effective treatments to improve walking (n = 6, 38%) and their ability to do sports/exercise, household tasks and work/voluntary work (each n = 5, 31%; Supplementary Materials Table S6).

Discussion

Through in-depth interviews with patients, this study found that patients diagnosed with late-stage CKD experience a variety of physical functioning limitations which impact various aspects of their lives. Using the concepts reported by the interviewed patients, a comprehensive conceptual model was developed summarizing the experience of patients with late-stage CKD (including patients with PKD) who have physical functioning limitations.

The most frequently reported physical functioning limitations identified in this study were walking up and down stairs and walking. Increased walking has been associated with a lower mortality in the general population and in patients with CKD [28, 29], although it is unclear whether this is directly associated with increased physical functioning. Patients also found ways to change or adapt their behaviour to accommodate their physical functioning limitations, including avoiding activities such as walking places or lifting heavy items. This suggests that the physical functioning limitations patients experience were not only caused by the symptoms they perceive to be directly associated with CKD but could be caused by the patients pre-emptively initiating behaviour changes to reduce activities to avoid physical functioning limitations or symptoms. With that, if an intervention were able to improve patient symptoms, and therefore their physical functioning ability, those improvements may not be captured by currently available COA tools (if they are not fit for purpose) and would be fully missed by any digital tools if the patients’ behaviour patterns meant they were purposely avoiding the activities assessed. Another important finding was that almost all patients who reported physical functioning limitations also reported negative impacts on their ability to participate in activities, including general household tasks and social interactions. Reductions in social interactions can lead individuals to feel isolated and lonely, both of which have been associated with increased mortality in the general population [30, 31].

The concepts included in the comprehensive conceptual model on physical functioning limitations in patients with late-stage CKD were primarily identified during the patient interviews in this study rather than during the TLR or previous patient interviews [7, 23], highlighting the importance of talking with patients about their experiences. In addition to exploring how physical functioning limitations affect various aspects of the lives of patients with late-stage CKD, this study investigated patients’ perceptions of how concepts relate to one another. The comprehensive conceptual model developed in this study only includes relationships between concepts when the patients themselves made the connection. This is due to relationships between concepts not being a focus of this study, so there may be other relevant relationships that have not been included in this conceptual model. In this study, relationships between concepts were typically found to be perceived as unidirectional and lead to broader negative impacts on different aspects of patients’ lives. For example, some patients reported having their physical functioning limitations (such as difficulty undertaking prolonged physical activity) result in behaviour changes (such as avoiding activities) or reductions in activity participation (such as difficulties doing housework or participating in exercise). Patients pre-emptively avoiding or altering activities so as not to experience negative symptoms or physical functioning limitations demonstrates the importance of understanding patients’ behaviours within their experience of physical functioning limitations. It is also of note that patients reported relationships between certain concepts differently; whereas some patients reported symptoms causing physical functioning limitations (fatigue leading to walking limitations), others reported physical functioning limitations causing symptoms (walking up and down stairs leading to fatigue). Understanding how the different aspects of the patient experience relate to one another provides further context and a more holistic understanding of how patients experience a disease.

The interviewed patients reported that the physical functioning limitations they experience typically have at least a moderate impact on their lives (over two-thirds reported an overall impact rating of ≥ 5 out of 10). This is supported by the majority of concepts being reported by patients spontaneously, which suggests the impacts of physical functioning limitations regularly affect patients and so are readily on their minds. Patients experiencing physical functioning limitations, and the associated negative impacts, may also have reduced HRQoL [32, 33]. Reductions in HRQoL have been associated with increased mortality in both healthy individuals and patients with CKD [34, 35]. It is important to recognise that the scores may have been influenced by how patients feel once they have accepted their condition and introduced behaviour changes. Acceptance of a health condition, such as CKD, can positively impact patient HRQoL [36]. Consequently, patients who have accepted their condition may report that their lives have been impacted less than patients who have not.

Patients reported that out of the symptoms they associated with their physical functioning limitations, alleviation of fatigue would have the largest effect on their physical functioning. They also expected that an effective new therapy would improve their physical functioning, particularly walking activities. This is consistent with the finding that all 23 patients who reported concepts associated with physical functioning limitations disclosed a lack of energy/tiredness/fatigue, which is commonly described for patients with CKD [23, 37], and that most patients also reported walking limitations of some form. Consequently, targeting the symptom of fatigue may allow a large proportion of patients to become more active and experience the additional benefits associated with increased physical function. Awareness of which concepts affect, and are most relevant to, patients can allow more tailored treatment approaches to be provided and can inform the design of more patient-focused clinical trial endpoints.

By talking with patients about their experiences of a condition it is possible to build a more complete understanding of how patients are affected physically and in their daily lives. Consequently, the findings from this study could be used as a guide when designing or evaluating fit-for-purpose instruments to assess experiences of patients with CKD stages IV–V who have physical functioning limitations. Activity monitors are used to measure differences or changes in patient physical activity and function [36, 38] and could be used to assess some of the concepts reported in this study, such as walking limitations (including duration and speed) and behavioural impacts (including taking breaks and reducing pace). However, other information which can provide more context about a patients’ experience of a condition, such as understanding patient behaviours and the environments they live in, can be found using COAs, especially those that are classified as patient-reported outcomes (PRO; a measurement based on a report obtained directly from patients about their experience of disease) or observer-reported outcomes (ObsRO; a measurement of patient experience of disease provided by someone other than the patient or a health professional, such as a parent or a caregiver) [14,15,16,17]. Such tools can evaluate parts of the patient experience, such as symptoms which occur when carrying out an activity (including shortness of breath following walking) and behaviour changes (including avoiding activities), or when identifying which impacts patients feel are most bothersome or challenging. Capturing patient experiences provides context which explains potential nuances that may exist when digital devices are used on their own. Combining measurement strategies, such as PRO/ObsRO measures and activity monitors, can provide a more holistic understanding of the patient experience and could be used to evaluate treatment benefits of therapeutic interventions and how they affect physical functioning limitations in patients with CKD.

Study Limitations

The small size of the subgroups of patients with CKD stages IV or V meant that this study had to focus on the cohort as a whole (the ‘late-stage’ CKD group); it also resulted in patients with PKD being recruited, who may experience limitations in physical functioning differently compared with other causes of CKD. However, the achievement of saturation of concepts associated with physical functioning limitations within this study supports that sufficient data were collected [18], indicating that the number of patients recruited was suitable for this study. The population was skewed towards patients who were white (80%) and from the USA (100%) in addition to there being patients with PKD interviewed (32%), meaning the population may not be fully representative of patients with late-stage CKD. The study population also contained a higher proportion of female patients; however, this could reflect the higher prevalence of CKD stage IIIa–V typically found in female individuals than in male individuals [39,40,41]. The long-term nature of CKD could have resulted in patients adapting to, and accepting, the changes in physical functioning associated with their condition, leading them to view reductions in physical functioning as less severe.

Conclusions

This study demonstrates that patients with late-stage CKD (including those with PKD) who are not receiving dialysis and are experiencing physical functioning limitations report a range of impacts on their daily lives. Patients reported the types of physical functioning limitations experienced and how they affect other aspects of patients’ lives, including behaviour changes and reductions in activity participation. The comprehensive conceptual model summarizes the concepts reported during the patient interviews and illustrates how patients with late-stage CKD perceive the impact of physical functioning limitations and how reported concepts affect and relate to one another. Using patients’ direct input to capture how they are affected by their condition provides a holistic understanding of physical functioning limitations experienced by patients with late-stage CKD. Input from patients summarized in the conceptual model may also inform the development of, or improve the use of, quantitative assessment methods such as digital activity monitors and COAs, in clinical practice and future clinical studies.