Frailty in focus: a scoping review of frailty instruments on behalf of the Kidney Disease Aging Research Collaborative

Structured Abstract

Background

Frailty is a multi-system syndrome of decreased physiologic reserve with high prevalence, early incidence, and prognostic significance in kidney disease. Apart from the Physical Frailty Phenotype (PFP), less is known regarding psychometric properties of other instruments. We critically appraise the validity and reliability of frailty instruments across the kidney disease continuum, acknowledge limitations, and highlight knowledge gaps.

Methods

Following PRISMA-ScR guidelines, we searched PubMed, EMBASE, Cochrane, CINAHL, Web of Science, ClinicalTrials.gov, and PsycInfo from website inception through 9/2024. Eligible studies applied a validated frailty instrument apart from the PFP to a kidney disease population.

Results

We identified 136 articles after screening 4,048 initial results. The most commonly cited instruments were the Clinical Frailty Scale (CFS; N=56), FRAIL Scale (N=30), and Edmonton Frail Scale (N=16). Most studies included adults receiving hemodialysis (N=85) and with chronic kidney disease (N=39). Median age ranges were 53–83 years. Most frailty instruments demonstrated predictive validity for mortality and hospitalizations. Concurrent validity was most frequently demonstrated between frailty and older age, female sex, greater comorbidities, and lower albumin. Seven studies reported reliability. While some instruments were feasible (CFS, FRAIL scale), their measurement could result in higher frailty prevalence compared to the PFP. Existing instruments do not capture the full spectrum of psychosocial and physiologic domains of frailty.

Conclusions

The CFS demonstrates the strongest validity, apart from the PFP, although its use may result in higher measured frailty prevalence. Further research should test the feasibility of screening for frailty in clinical practice; the psychometric properties (i.e., responsiveness) of frailty instruments in younger adults, those with acute kidney injury, kidney transplant recipients, and those receiving conservative kidney management; and whether adding psychosocial and/or physiological markers improves frailty measurement validity. Addressing these gaps will facilitate wider frailty measurement in kidney disease research and aid adoption into practice.

Introduction

Frailty is a multi-system syndrome of decreased physiologic reserve leading to increased vulnerability for poor health outcomes.¹ Frailty, a broad construct that includes physical, cognitive, and psychological domains, originated as a concept in the gerontology literature using observations among community-dwelling older adults. The prevalence of frailty in those with kidney failure is higher than in those with chronic kidney disease (CKD);² frailty is also highly prevalent in kidney transplant candidates and recipients.³ Across all groups of nephrology patients, frailty occurs earlier than would be expected based on chronologic age and has been associated with a myriad of complications.^2,4,5 Given the pervasiveness of frailty across the kidney disease continuum, measurement accuracy is crucial. Frailty is also a potential risk factor for acute kidney injury (AKI) and is a predictor of worse outcomes in those with AKI.^6,7

National and international nephrology specialty societies have recommended the routine measurement of frailty in kidney disease care.^8,9 Despite this, feasibility studies have demonstrated that frailty instruments are not widely implemented.^10–12 There is significant heterogeneity in the instruments currently being used to measure frailty in practice.¹³ As such, patients with kidney disease who may most benefit from risk stratification, rehabilitation, and participation in patient-oriented clinical trials may remain unknown to clinicians and investigators. The Physical Frailty Phenotype (PFP) is the most widely cited frailty instrument in kidney research. However, there remains significant heterogeneity in frailty instruments used in other studies.¹⁴ One scoping review noted that a total of 40 different frailty instruments had been applied to research in CKD.¹⁴ This may pose a challenge to investigators who wish to compare studies that use different frailty instruments.

With this scoping review, we take initial steps towards addressing these challenges. We move beyond existing reviews of frailty in kidney disease by: 1) describing the content, scoring, and potential limitations of frailty instruments validated in patients with kidney disease; and 2) summarizing the validity and reliability of each frailty instrument across the kidney disease continuum. The PFP has been widely reported in kidney disease, is associated with a diverse range of objective and patient-reported outcomes and has robust evidence of validity. ^15–18 Thus, we focused on other validated frailty instruments that have been applied to patients with kidney disease: Clinical Frailty Scale (CFS), Edmonton Frail Scale, FRAIL Scale, Frailty Index, Geriatric 8, Groningen Frailty Indicator, PRISMA-7, Study of Osteoporotic Fractures Index, and Tilburg Frailty Indicator. We conclude with a critical appraisal of gaps in knowledge with regard to frailty measurement and discuss potential clinical applications of frailty instruments.

Methods

Protocol registration, eligibility criteria, and information sources

Our manuscript constitutes a large scoping review.¹⁹ We performed this review in accordance with the framework proposed by Arksey and O’Malley²⁰ and used the Preferred Reporting Items for Scoping Reviews (PRISMA-ScR) reporting guideline (Supplementary Table 1).²¹ We registered our protocol with the Open Science Framework on September 12, 2024 (https://doi.org/10.17605/OSF.IO/PQVKG). Studies were only included if they used validated frailty instruments applied to adults with CKD, kidney failure, kidney transplant, or AKI in inpatient or outpatient settings. CKD was defined as the presence of markers of kidney damage [i.e., Albuminuria (ACR ≥30 mg/g)] or decreased GFR (<60 ml/min/1.73 m²) for three months or longer as described by the National Kidney Foundation.²² Kidney failure was defined by the receipt of hemodialysis (HD) or peritoneal dialysis (PD). Kidney transplantation was defined by a history of a kidney transplant with a functioning graft. We followed Kidney Disease: Improving Global Outcomes (KDIGO) guidelines in defining AKI as abnormalities in kidney function and structure for less than three months.²³ Studies were excluded if they focused solely on pediatric patients, were written in languages other than English, or were protocols, review articles, or abstracts. We also excluded studies in which frailty was used as a covariate, studies that only tested the PFP, qualitative studies, studies in which no significant associations between frailty and other factors were found, and studies in which no validity or reliability testing was reported. As psychometric properties of an instrument cannot be measured in the setting of an active intervention, clinical trials were excluded.

A medical librarian (JM) developed the initial search strategy using keywords and subject headings related to nephrology and frailty, which were iteratively modified in consultation with the investigative team. The search was then tested and peer-reviewed by another librarian using the Peer Review of Electronic Search Strategies (PRESS) checklist, before being translated into other databases.²⁴ We searched the following bibliographic databases: EMBASE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Health and Psychosocial Instruments (HaPI), PsycInfo, Cumulated Index in Nursing and Allied Health Literature (CINAHL), and Web of Science from inception to September 5, 2024 (Supplementary Table 2). The results were uploaded to Covidence (Covidence, Melbourne, Australia).

Study selection

Eleven team members were trained in Covidence using ten studies each. The same group was then split into pairs and independently screened additional article titles and abstracts. This was followed by a review of full text articles and data extraction. During the title and abstract screening, investigators ensured articles included kidney disease patients, measured frailty, and applied a valid study design. At the full text review stage, inclusion criteria were restricted to frailty instruments that were validated or had undergone reliability testing.

Data charting and synthesis of results

The investigative team developed a data extraction template. Data extraction was completed by two independent investigators, and a third checked for consensus. Variables extracted included publication information (author and country in which the study was conducted), methods (study design, sample size), participant characteristics (type of kidney disease, mean or median age), frailty instrument (including adaptations from original instrument, if applicable), and psychometric properties (inter-rater or test-retest reliability, criterion validity, content validity, construct validity). Supplementary Table 3 describes the psychometric definitions applied to data extraction.²⁵

All conflicts were resolved by the leaders of the investigative team (DN, MMD, IM) at each phase through group discussion. A preliminary table of data extraction was downloaded from Covidence to Microsoft Excel. Team members then further reviewed results for consistency and accuracy. DN and IM individually re-reviewed the accuracy of psychometric data of all studies.

Results

Study Screening

A total of 4,048 studies were imported for screening. After removal of duplicates, 2,639 studies were screened based on title and abstract, with 1,847 studies excluded. 792 articles met inclusion criteria for full-text review. The most common reason for exclusion was “only measuring the physical frailty phenotype” (N=161), which was outside the scope of this review. 136 articles were included in the data extraction phase (PRISMA flow diagram: Figure 1).

Figure 1:

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Flowchart of Identification and Screening Process

Study Characteristics

Table 1 summarizes information on the characteristics of the most commonly used (except PFP), validated frailty instruments in the literature.^{1, 26–34} Table 2 presents information about study characteristics, evidence of psychometric validity and/or reliability, and study findings highlighting one study each from the top six most frequently cited instruments in kidney disease literature. A table with all articles is available in Supplementary Table 4. ^6,35–169 Except for the PFP, which was beyond the scope of this review, each instrument in Table 1 was included in at least one study in Supplementary Table 4. Figure 2 is a visualization of the frequency and type of the most commonly cited frailty instruments in the kidney disease literature, stratified by kidney disease population subtype. Figure 3 visualizes the evidence of psychometric testing for the most commonly cited frailty instruments in kidney disease populations.

Table 1:

Most frequently cited frailty instruments

Instrument Name	Domains	Original study population	Scoring	Information source	Limitations
Edmonton Frail Scale26	physical (physical function, nutritional status, polypharmacy), cognitive (cognitive dysfunction), psychological (mood), social (isolation, support)	Adults aged 65 and older referred for a comprehensive geriatric assessment in acute care wards, rehabilitation units, day hospitals and outpatient clinics in Edmonton, Alberta	0–17; 17 represents the highest level of frailty	patient answers questionnaire/interview questions and completes two performance-based items	Requires time to be administered in-person. Limited coverage of some domains, for example cognition is only assess by clock drawing.
Groningen Frailty Indicator27	physical (physical function, comorbidity burden, disability, fatigue) cognitive (cognitive dysfunction), social (isolation), psychological (mood)	Adults aged 65 and older from the Netherlands - hospital inpatients, nursing home residents and community-dwelling elderly	0–15; 4 or higher represents moderate to severe frailty	patient self-report	Scores do not distinguish between which domains are driving the overall score therefore different frailty related problems can lead to score considered frail. Self-reported, which may result in bias or inaccuracy in answering questions if there is cognitive dysfunction. Lack of objective physical performance measures.
Physical Frailty Phenotype1	physical (physical function, physical strength, weight loss)	Adults aged 65 and older from the Cardiovascular Health Study	0–5; frail (≥3); prefrail (1–2); 0 (robust)	patient self-report and objective physical performance assessment	Only measures physical frailty components. Requires in person evaluation for measuring grip strength with dynamometer and speed with timed walk.
Frailty Index28	physical function (comorbidity burden, physical function, disability), cognitive (cognitive dysfunction), psychological (mood)	Older adults (mean age 82) from the Canadian Study of Health and Aging	92 binary (yes/no) variables, expressed as q, the ratio of variables present to absent. Higher FI indicates greater degree of frailty and mortality risk. Generally, a ratio of 0.08 to 0.25 indicates prefrailty and greater than 0.25 indicates frailty.	medical record	Medical record must be extensively reviewed. Requires at least 30 health variables to be included. Numerous versions can lead to difficulty determining which one to administer in clinical practice and confusion when interpreting research studies that use different versions.
PRISMA-729	physical (comorbidity burden, physical function), social (support)	Adults aged 65 and older in Canada	0–7; frail (≥3)	patient self-report	Relies exclusively on patient self-report
Clinical Frailty Scale30	physical (comorbidity burden, physical function, weight loss), cognitive (cognitive dysfunction)	Adults aged 65 and older from the Canadian Study of Health and Aging (CSHA)	From 1 to 9; Ranging from 1 being very fit and 9 being terminally ill	clinician report	Requires trained clinician to evaluate subject. May over-estimate frailty in patients with stable long-term disabilities.
FRAIL Scale31	physical (physical function, comorbidity, fatigue, weight loss)	African American Health (AAH) Project: African Americans aged 49 to 65	0–5; frail (3–5), pre-frail (1–2), robust (0)	clinician report	Only measures physical frailty components. Other sources of physical limitations may cause instrument to misclassify patients.
Study of Osteoporotic Fractures Index32	physical (weight loss, physical function, fatigue)	Women aged 65 and older in the Study of Osteoporotic Fractures	0–5; frail (2–3); prefrail (1–2); robust (0)	patient self-report and objective physical performance assessment	Originally developed in women
Tilburg Frailty Indicator33	physical (comorbidity, physical function, weight loss), psychological (mood), social (isolation, support)	Adults aged 75 and older randomly drawn from a register in The Netherlands	0–15; higher score indicates high level of frailty	patient self-report	Self-reported scoring, which may be a source of bias. Low internal consistency in psychological and social frailty domains, as well as low predictive capacity for the psychological and social frailty components.
Geriatric 834	physical (comorbidity burden, weight loss, nutrition, physical function, polypharmacy) psychological (mood), cognitive (cognitive dysfunction)	Adults aged 70 and older with malignancy	0–17; lower score indicates higher risk of frailty. Cut off of less than 14 identifies patients who may benefit from comprehensive geriatric assessment	clinician report	Only validated to screen for patients who would benefit from CGA, not as a diagnostic tool to identify frailty. Mostly validated in oncology populations.

Abbreviations: FI: Frailty index; PRISMA-7: Program of Research to Integrate Services for the Maintenance of Autonomy-7; FRAIL - Fatigue, Resistance, Ambulation, Illnesses, and Loss of Weight; CGA: Comprehensive Geriatric Assessment;

Table 2:

Highlights of validity and reliability of frailty instruments across kidney disease populations

Number of times instrument cited	Frailty Instrument	Criterion validity	Other validity	First Author Year	Country	Study design	Participant diagnoses and/or treatment	Prevalent or Incident?	Mean age (SD)	Median Age (IQR)	Min. age
56	CFS	Predictive validity: frailty associated with mortality on unadjusted analyses (OR 2.44, 95% CI 0.37–15.7)		Abraham 202335	United Kingdom	Prospective cohort study	Peritoneal dialysis	Prevalent		56 (range 42–65)
30	FRAIL Scale	Concurrent validity: frailty cross-sectionally associated with age, presence of diabetes, and lower albumin on unadjusted analyses (no Cis reported). Predictive Validity: Frailty independently associated with vascular access failure after a median follow-up of 15.7 ± 8.8 months (aHR 2.63, 95% CI 1.03–6.71)		Chao 2017b64	Taiwan	Prospective cohort study	Facility hemodialysis	Prevalent	68 (11.8)
16	EFS	Concurrent validity: frailty independently associated with higher cumulative inpatient, emergency, and total health-care visits (CIs not reported)		Adame Perez 201936	Canada	Cross sectional study	CKD	N/A		70 (65–74)
7	Tilburg Frailty Indicator	Concurrent validity: frailty was associated with older age, a longer duration of dialysis, a higher prevalence of diabetes mellitus, having a higher number of comorbidities, a lower albumin, a higher phosphorus, higher depressive symptom severity, and greater anxious mood on unadjusted analyses. Frailty was independently associated with older age, a higher number of comorbidities, having a nuclear family, and having a lower albumin.		Gong 202285	China	Cross sectional study	Facility hemodialysis	Prevalent	62.0 (13.4)
5	Groningen Frailty Indicator	Predictive validity: higher frailty associated with functional decline or death (OR 1.97, 95% CI 1.05–3.68).	Convergent validity: 46% of participants were found to be frail using PFP, while 62% were frail according to GFI.	Goto 201986	Netherlands	Prospective cohort study	Facility hemodialysis; Peritoneal dialysis	Incident	75 (7)		65+
		Concurrent validity: Severely dependent participants were more frail according to GFI (92% versus 39%) compared with independent participants
3	PRISMA-7	Predictive validity: frailty independently associated with mortality (HR 4.28, 95% CI 1.22–14.98)		Ali 201838	United Kingdom	Prospective cohort study	CKD	N/A		Frail: 77.4 (65–92), nonfrail: 76.7 (65.87)	65+

Abbreviations: CFS: Clinical Frailty Scale; EFS: Edmonton Frail Scale; Program of Research to Integrate Services for the Maintenance of Autonomy-7 - PRISMA-7; OR: odds ratio; CI: confidence interval; aHR: adjusted hazard ratio; HR: hazard ratio; GFI: Groningen Frailty indicator; PFP: Physical frailty phenotype; CKD: chronic kidney disease; N/A: not applicable

Figure 2:

Frequency and type of the most commonly cited frailty instruments, stratified by kidney disease population subtypes

Figure 3:

Evidence of validity and/or reliability across the most commonly cited frailty instruments in kidney disease

The 136 studies (Supplementary Table 4) span a range of ages, countries, and the kidney disease continuum. Of the studies that reported this information, the mean and median age ranges were 45–84 years and 53–83 years, respectively. The studies included individuals with AKI (N=4), CKD (N=39), receiving facility HD (N=85), receiving PD (N=36), having received a kidney transplant (N=12), or receiving conservative (non-dialysis) management of kidney failure (N=2). One study did not specify dialysis type. Studies originated from 23 countries, with the most common countries being the United Kingdom (N=28), China (N=18), and Taiwan (N=14). Three studies included both prevalent and incident dialysis patients; 85 included only prevalent dialysis, and 16 only incident dialysis. The remainder of the studies did not examine people on dialysis or were unclear about dialysis type.

Characteristics of frailty instruments used

For the purposes of this scoping review, we excluded studies of only the PFP (N=161). The next most commonly used frailty instruments were the Clinical Frailty Scale (N=56), FRAIL scale (N=30), and Edmonton Frail Scale (EFS; N=16). Multiple studies evaluated more than one frailty instrument (N=14).

While instruments covered a broad range of potential domains of frailty (e.g. physical, psychological, cognitive, and social), the domains of physical function and physical symptom burden were most commonly described in each instrument. The next most commonly described domain was cognitive, and psychosocial domains were least frequently described. Except for the FRAIL Scale, all instruments were originally developed in adults aged ≥65. Some instruments rely exclusively on patient self-report (Program of Research to Integrate Services for the Maintenance of Autonomy-7, Tilburg Frailty Indicator, Groningen Frailty Indicator, FRAIL Scale), others often require an extensive medical record review (Frailty Index), and some require in-person physical assessments (Study of Osteoporotic Fractures Index, PFP, EFS). Notably, the Study of Osteoporotic Fractures Index was originally developed in a population of women.

Validity and reliability

Predictive validity for mortality and hospitalizations was demonstrated across all frailty instruments, and, in particular, the CFS. The most frequent demonstrations of concurrent validity were associations between higher frailty and older age, female sex, higher comorbidity burden, and lower albumin. Convergent validity across frailty instruments was most significant between the FRAIL Scale and CFS (r=0.5–0.83). Seven studies reported the reliability of frailty instruments in kidney disease (six demonstrated inter-rater reliability: three for the CFS, two for FRAIL Scale, one for Frailty Index, and only one demonstrated test-retest reliability for EFS). The specific validation findings for each of the four most commonly used frailty scales in this review are below.

Clinical Frailty Scale

In studies of acute kidney injury (N=4), all showed predictive validity. In studies of CKD (N=7), five studies showed concurrent validity and two showed predictive validity. In studies of HD (N=34), 18 studies showed concurrent validity and 16 showed predictive validity. Similarly, in studies of PD (N=15), six studies showed concurrent validity and nine showed predictive validity. In studies of kidney transplantation (N=4), three showed predictive validity while one examined concurrent validity. Only one study examined the concurrent validity of conservative kidney management.

FRAIL Scale

There were no studies examining the FRAIL Scale in AKI. In studies of CKD (N=8), three, four, and two studies examined concurrent, predictive, and convergent validity, respectively. In studies of HD (N=19), 13 measured concurrent validity, seven measured predictive validity, and three evaluated convergent validity. Within studies of PD (N=5), two studies looked at concurrent validity, three evaluated predictive validity, and one evaluated convergent validity. Only one study with kidney transplant patients evaluated the FRAIL scale with both concurrent and predictive validity.

Edmonton Frail Scale

No studies examined the EFS in participants with AKI. In studies of CKD (N=5), all showed evidence of concurrent validity and one of predictive validity. In studies of HD (N=8), six showed concurrent validity, and two showed predictive validity. The one study of PD showed concurrent validity. The single study examining conservative kidney management showed concurrent validity.

Tilburg Frailty Indicator

No studies examined the Tilburg Frailty Indicator in participants with AKI, CKD, or receiving PD. In studies of HD (N=5), four showed evidence of concurrent validity and one of predictive validity. In studies of kidney transplant (N=2), both showed concurrent validity.

Frailty Index

Notably, the Frailty Index was originally the third most commonly cited frailty instrument in our review. As was the original intent of the creators of the Frailty Index, investigators applying this instrument in their studies often adapted it (over 15 variations attributed to multiple authors and studies). Using the Frailty Index’s underlying deficit accumulation theory, the adapted versions of the Frailty Index included differing numbers of items capturing unique deficits in domains of health, ranging from as few as five items to as many as 58 items. As no studies used the Frailty Index in its original form, we are unable to comment on the psychometric strength of the original Frailty Index in kidney disease.

Discussion

In this scoping review of frailty in patients with kidney diseases, we found that apart from the PFP, the CFS was the most commonly used tool and demonstrated the strongest validity, although its use may result in higher measured frailty prevalence. When selecting a frailty instrument for use in research or clinical care, different tools have properties that can be useful for answering different research questions or addressing distinctive clinical problems. However, most frailty instruments in our scoping review demonstrated predictive validity for mortality and hospitalizations. In terms of kidney disease-specific outcomes, the CFS^84,131 was associated with technique failure in PD and could be used prognostically to consider technique success in these patients. Some instruments demonstrated predictive validity in terms of predicting dialysis access failure in facility HD and PD, but given the studies’ small sample sizes, robust conclusions cannot be drawn.^64,113 The CFS⁵⁷ and FRAIL Scale¹²⁶ were both found to be associated with decreased chance of being listed for a kidney transplant as well as an increased risk of complications while on the waitlist. Only CFS was used for individuals with AKI, and frailty was predictive of mortality.^6,118,148 We also identified the following knowledge gaps, which we recommend addressing in future research.

First, there is no one gold standard frailty tool for clinical implementation in kidney disease. The existing literature suggests that different tools can be used for various purposes. For example, identifying patients for pre-kidney transplant prehabilitation may benefit from subjective measures to capture patient-reported problems, while risk prediction may benefit from objective measures. Furthermore, multiple tools may be useful for a two-step screening. Clinicians may embed either CFS or the FRAIL Scale into clinical practice as a screener to identify patients who would benefit from a more in-depth test, such as the PFP, most useful for patients with sarcopenia and physical performance limitations.¹⁷⁰ In our review, the CFS was the most commonly reported instrument after the PFP and had high clinical utility due to its simplicity; it is measured solely using a physician’s clinical impression (although informed by their knowledge of the patient), making it an ideal screener. However, it is worth noting that the CFS captures domains of functional status and may thus be less sensitive to early physiologic changes that occur in pre-frail patients and may not correlate with objective measures.^171,172 The next most commonly used instrument, the FRAIL Scale, is also potentially easily adapted to clinical practice because of its brevity. Thus, future studies should identify the most feasible tool(s) for clinical implementation.

Second, none of the studies in our scoping review compared psychometric values of frailty measures between younger and older patients with kidney disease. Yet, studies have demonstrated differences in PFP by age.^3,173,174 Most validated frailty instruments were originally developed in adults aged ≥65.^1,28,30 However, younger adults with kidney disease exhibit a high frailty prevalence and thus should be included in future studies.^173,175 Younger adults, including those with kidney disease, tend to have fewer comorbidities.¹⁷⁶ Therefore, instruments that emphasize total comorbidity burden to measure frailty may misclassify younger adults as robust. Furthermore, there is clinical heterogeneity in the severity of kidney disease across the kidney disease continuum, which may affect frailty cut-offs in younger patients.

Third, not all instruments in our scoping review included psychosocial domains or fully captured physiological causes of frailty. Lack of psychosocial domains is a key knowledge gap in frailty measurement among patients with kidney disease, given their high physical and emotional symptom burden.^177,178 The full spectrum of physiologic causes of frailty is not captured in any existing frailty instrument. The Frailty Index captures 30–70 deficits, and most other frailty instruments measure physical performance limitations (i.e., manifestations of sarcopenia).¹⁷⁹ Yet, physical limitations can be difficult to capture through self-report, as patients with kidney disease may underestimate the severity of physical performance limitations,¹⁷¹ resulting in frailty misclassification. Other factors, such as endocrine disruption, inflammation, and endothelial dysfunction, are also thought to contribute to frailty^180–182 and are not fully represented in existing frailty instruments. Development of frailty instruments that include biomarkers of these conditions is needed.

Fourth, none of the Frailty Indices that are specific to patients with kidney disease have been replicated or validated across studies and populations.^87,98,158 The original Frailty Index can be perceived as more resource-intensive than other frailty instruments, as it requires access to comprehensive electronic health record data.²⁸ However, the Frailty Index was uniquely developed to capture multiple domains of health, including conditions that tend to accumulate with chronologic age. Importantly, it excludes traits that rely solely on visual inspection, physical appearance, or subjective self-report.¹⁸³ Given these qualities, testing the validity and reliability of the Frailty Indices specific for patients with kidney disease is an important knowledge gap to address. Further, future research may investigate whether such an index is appropriate to use on AKI, dialysis, and kidney transplant patients, or whether different factors are needed when utilized across the kidney disease continuum.

Fifth, few frailty instruments in our scoping review were studied in patients with AKI, kidney transplantation, or who chose conservative kidney management. AKI is often detected in hospital settings and is frequently associated with inflammatory conditions,¹⁸⁴ making it highly likely to be associated with frailty. While still present, physical performance limitations may be less severe in AKI¹⁸⁵ and kidney transplant patients¹⁸⁶ as compared to kidney failure; thus, we are able to better measure physiologic reserve, without identifying functional limitations as a proxy for frailty. Very few studies in our review specifically tested frailty instruments in patients who chose conservative management. A patient’s decision for conservative management usually centers around concerns over quality of life, with fears of dialysis worsening functional status.¹⁸⁷ Accurate assessment of frailty in these patients could provide important prognostic and decision-making information for the patients, caregivers, and physicians at the time of this decision.^77,188,189

Sixth, few studies in our scoping review tested for reliability across the kidney disease continuum. Of the studies that did test reliability, it was mainly tested in patients receiving HD. No reliability testing was performed in kidney transplant recipients or in those with AKI. This lack of reliability testing is an important gap, as an ideal frailty instrument should measure changes in frailty as kidney disease progresses and potentially improves with interventions such as a kidney transplant.

Seventh, we did not find any studies in our scoping review that compared changes in frailty with progression of or worsening kidney disease. There is likely a bi-directional relationship between kidney disease and frailty. Examining the changes in frailty alongside the progression of kidney disease can reveal insights into shared pathways (including inflammation, metabolic disorders, and sarcopenia) that contribute to both conditions.¹⁹⁰ Further, screening for frailty at earlier stages of kidney disease provides more opportunity for intervention both on frailty and kidney disease; thus, this is an important opportunity for future study.

Finally, given that no randomized trials that aim to treat frailty in kidney disease were identified in our study, data on responsiveness, or the aspect of validity in which an index measures changes over time or in response to an intervention, were not available. Ultimately, more studies demonstrating the predictive validity of frailty instruments for kidney disease-specific outcomes, such as access failure and dialysis initiation, and more studies that apply validated frailty instruments to large-scale trials are needed.

Strengths of our review include our iterative process, our broad search across nine bibliographic databases to minimize bias, our investigative team’s training and expertise, and our use of an established framework and reporting guidelines. While we did not critically evaluate the quality of each study included in our review, nor the impact of varying confounding factors across studies, our evaluation of the accuracy of validity and reliability testing in each study supports the robustness of each study’s results. Further, we only accounted for studies written in English. Finally, we only included studies quantifying significant associations between frailty and outcomes, which may introduce selection bias and overrepresent positive findings; however, as our goal was to present a review of the literature rather than an overall effect size, this likely has minimal impact on our findings.

With this scoping review, we aimed to arm investigators and clinicians with the information they need to make informed decisions about which existing frailty instruments to use in kidney disease research and clinical care.

In our review, CFS and FRAIL Scale were the most common instruments after the PFP and demonstrated validity and reliability in kidney disease patients; clinicians may implement these tools as screeners prior to using more resource-intensive instruments. Clinicians may also continue to apply validated instruments according to the patient of focus, and where they fall on the kidney disease continuum. Further research is needed to provide insight into the eight knowledge gaps.

Supplementary Material

Supplementary Material

Supplementary Table 1: PRISMA-ScR Checklist

Supplementary Table 2: Search Strategies

Supplementary Table 3: Psychometric testing definitions

Supplementary Table 4: Full Table 2: Validity and reliability of frailty instruments across kidney disease populations

Key Points.

1. The Clinical Frailty Scale has the strongest psychometric validity in kidney disease apart from the Physical Frailty Phenotype.

2. Existing frailty instruments have strong predictive validity for mortality and hospitalizations across kidney disease populations.

3. Future work should test validity in younger adults, psychosocial and physiologic domains, and use of frailty instruments as screeners.