Standardised definitions are required before frailty can be routinely assessed in clinical practice

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Left to right: Nicholas Inston, Külli Kuningas, Adnan Sharif.

Earlier this year, a retrospective study published in the American Journal of Kidney Diseases came to the conclusion that “frailty may be useful for informing clinical decision-making regarding choice of vascular access”—based on findings from the United States Renal Data System (USRDS). This paper was of great interest to Nicholas Inston, Külli Kuningas and Adnan Sharif (Queen Elizabeth Hospital, Birmingham, UK), all of whom are currently working to evaluate the definition and role of ‘frailty’ in dialysis patients in the UK.

“If you look at general definitions of frailty, they are often age-related, and frail patients are seen as being an older age group,” says Kuningas. “But there are signs that CKD [chronic kidney disease] patients tend to be frail at a younger age compared to the general population, which is why having a frailty concept that is not based on age is important.” Inston adds: “I think the shift is away from using age as a parameter, and towards using frailty, on the basis that frailty is at least a functional measure— whereas age is just a number for a lot of patients.”

“We have some 40-year-old patients who are not fit for a transplant, and some 80-year-old patients who are,” he continues. “If a patient has been on dialysis for 20 years, they will almost certainly be frailer than somebody of the same age who has not. If they have had a kidney transplant in those 20 years of ESKD [end-stage kidney disease], they will probably be less frail than somebody who has been on haemodialysis during that time. So, again, it is very much patient-specific rather than generic, and that is the reason for trying to use this as a measurement.”

In a Journal of Vascular Access paper published last year, Inston and Kuningas posit that moving towards a standardised, effective method of frailty assessment chimes with the more individualised, collaborative view to vascular access care outlined in the 2019 Kidney Disease Outcomes Quality Initiative (KDOQI) guideline update. They also note that a universal, reproducible approach to frailty scoring will likely be a “key component of ongoing future access care”—before concluding that further research is required to identify criteria and scoring tools that best lend themselves to the dialysis access space.

While these guidelines recommend pivoting towards frailty, or ‘functional status’, as opposed to simply using age, the definition of frailty and precisely how it should be implemented remains murky.

Standardised definitions

Speaking to Renal Interventions, Kuningas notes that the concept of using frailty as a clinical yardstick is not entirely new, having been around since the early 2000s, but the primary focus has been on elderly patients for much of that time, and it is only during the past five years or so that broader definitions involving younger patient cohorts have really come to the fore. “This has been overdue,” she says. “There is a lot we do not know about frailty, and we need much more research, in particular on how we implement it into clinical practice.”

There are numerous frailty assessment tools that are currently available. The most commonly used of these is the clinical frailty scale (CFS), which involves a quick visual assessment, is utilised across many different conditions and works on a specific, grade-based system from 1–9. But, according to Kuningas, the CFS is far from perfect—not least because of the extent to which it is left open to clinician interpretation. “It is very subjective,” Kuningas claims. “The way I would assess someone may be different to how [a surgeon or a nephrologist] would assess someone. That is the main vulnerability of it.” She also says that the CFS only focuses on physical frailty indicators, despite the fact that frailty has numerous psychological and social ramifications for patients.

According to Kuningas, the relative overlap between frailty and sarcopaenia has led to muscle quantity and quality also being looked at as a potential adjunct to true patient frailty. A recent report in European Geriatric Medicine examined the association between a simple measure of muscle thickness, via ultrasound, and commonly used frailty measures. However, it ultimately concluded that “frailty is a multifactorial syndrome, and caution must be used in trying to screen for this condition with a single ultrasonic measure”.

And, as Kuningas notes, attempts to assess frailty measurement tools have often been conducted among patients aged 60 years and older. This exclusion of younger people is a problem, and makes it even more difficult to identify a single, universal frailty assessment approach, she believes.

Frailty and vascular access

“We know that some older patients have worse outcomes with fistulas, but that is still not a reason to rule out a fistula, because they [could] have worse outcomes with central venous catheters and other alternatives too,” Inston avers. He believes there are a number of ways in which frailty may impact vascular access outcomes—ranging from an increased likelihood of developing steal syndrome to greater risks of arteriovenous graft (AVG) infection or breakdown.

“We would also hypothesise that frail patients would tolerate high-flow fistulas less well than non-frail patients but, until we do the measurements, we really have no idea,” he continues. “The short answer is that we do not know for certain, and we cannot interpret how [frailty] will work until we start measuring it and doing more studies.”

Inston notes that another pivotal, yet unanswered question is whether frailty scoring should be performed early on in the kidney care pathway—to help adapt the longer-term treatment plan—or just for access planning. “I think doing it just for access planning may not be the right way forward,” he states.

“You need to get in early to see what a patient’s frailty is like when you are deciding on what dialysis modality they need. Are they going to be PD [peritoneal dialysis]-suitable or not? Are they going to be suitable for a transplant? That whole life-plan is based much more on frailty than age or any other parameter.”

Inston and Kuningas are also in agreement that frailty scoring, in addition to being performed early, should be done repetitively—as opposed to taking a single, one-time measurement. “I think it is also about what you are going to do about it once you have measured it,” Kuningas adds. “If somebody is pre-frail, how can we actually intervene and potentially reverse that? It is a multi-professional approach that needs to be incorporated into all aspects of care, and followed when the patient goes onto dialysis or receives a transplant.”

FITNESS study

The need for further research in this space is echoed by Sharif, who tells Renal Interventions that FITNESS (Frailty intervention trial in end-stage patients on haemodialysis) is seeking to build on the “surprising” lack of published data from the UK to date.

This randomised controlled study, he details, has enrolled close to 500 prevalent haemodialysis patients and clinically phenotyped them using a wide range of scoring systems—from the CFS, to sarcopaenia measurements, to self-reported frailty assessments. Referencing the FITNESS baseline cohort data published in the Clinical Kidney Journal earlier this year, Sharif highlights early indications that “regardless of which frailty score you use, a lot of haemodialysis patients are frail”.

“Depending on the score, it ranges from around 40–60%, and you also have a certain proportion who are vulnerable, or pre-frail, meaning you are only left with a small proportion who are not frail at all,” he continues. “While we have found that frailty is associated with a higher risk of hospitalisation and death, it is not a very good predictor of death by itself. So, I think the question is: how should we use frailty on a day-to-day basis?”

With this patient cohort now being followed for up to 10 years, more long-term data from FITNESS—relating to outcomes across different vascular access types, more in-depth hospitalisations data, and also how closely self-reported measures correspond to more objective frailty assessment tools—are expected further down the line.

Sharif notes that, save for leading work at Johns Hopkins University (Baltimore, USA) and “pockets” of research elsewhere in Europe, published data in this area remain scant. “We should probably be using frailty a lot more in our [clinical] decision-making,” he states, adding that striking a balance between the CFS and other assessments that are quicker and easier to perform, and others that take longer but involve functional measures and are therefore potentially more useful, is key.

“A lot will probably happen with frailty over the next few years, and I think it is only a matter of time before we need a consensus meeting to agree on whether we should be using frailty in patients starting dialysis, receiving vascular access, and being listed for transplantation,” Sharif concludes. “And, if so, which frailty tool do we use? I believe that is on the horizon, because there is a lot of talk about trying to establish more of a consensus moving forward.”

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