CME Slides Forum - P. Koufaki

A joint Congress by ERA-EDTA and ISN

ASESSMENT OF FUNCTIONAL CAPACITY IN CKD PATIENTS

Pelagia Koufaki, Stirling, UK

Chair: Naomi Clyne, Lund, Sweden

Rolfdieter Krause, Berlin, Germany

koufaki

Dr P. Koufaki
Department of Sports and Exercise Science
Stirling University
Stirling, United Kingdom

Well, thank you very much for the introduction and I would like to thank the organising committee for inviting me here as well.
In the next 20 minutes or so, I’m going to focus on some issues surrounding physical function assessment and evaluation in patients with kidney disease.

I would like to start by trying to define what we mean by physical function. It was quite difficult to find a consistent definition of what physical function means in the literature, so the best definition that I could come up with, was, that physical function is a collective term that actually describes a number of different abilities, skills that one may have or that one may be able to develop, and allows the individuals to actually go on with their daily lives or even pursue activities either for leisure or for social interaction. If you look at the literature for example, you will see a number of different terms like the ones that you see on the slide that probably have been used interchangeably to describe physical function but they probably also refer to different components of physical function.
Currently there’s no standardised way of assessing physical function in CKD patients, so what I’m proposing here to use, is this sort of framework, this sort of working framework that has been developed by Nagi and it describes basically the process from pathology to disability. I think this framework may be important and relevant to dialysis or CKD patients because disability is a side effect that is very commonly reported especially in the older more comorbid cohort of CKD patients.
By using this sort of framework I think it can help us to better categorise and characterise all the different physical function components that make up physical function overall. According to this, pathology, the presence of CKD in this instance, causes or leads to physiological or anatomical impairment documented in one or more body systems.
The persistence of this impairment usually leads to functional limitations and by functional limitations in this instance we mean functional limitations that can be documented as limitations in performance based tasks that look at the body as a whole, they don’t just focus on one or more body systems. The persistence of functional limitations subsequently leads to the development of disability and by disability, according to this model, we mean inability to perform a more socially defined role within specific social and cultural environments.

What this model basically describes are the changes or deterioration in physical function from pathology that can actually lead to development of disability. This may be relevant and applicable to CKD populations. Based on this model, physical function can be grouped in 3 main categories. I think all the relevant published information in the CKD population, all the different physical assessment tools that they have been used can actually relate to one of these components.

According to this framework, physical function can be characterised as physiological functional capacity and assessment tools that actually can measure or determine physiological functional capacity are basically mostly lab based, objective lab based tools often quite expensive equipment requiring specially trained personnel. This sort of component assesses physiological impairment that refers or relates to one or more isolated body systems.
Functional capacity, the next group categorisation of physical function, relates to assessing or characterising functional limitations. Functional limitations are mostly determined by use of simple performance based tasks such as the ones that you see on the list in the second group. Still objective assessment, but more simple to administer and easier to interpret as well.
Finally, the functional status component which relates to measuring and characterising disability is mostly assessed by self-reported questionnaires or by use of interviewing administering techniques.
This is the model that I will be using from now on in the rest of my presentation to describe and relate the different physical functional measurements to specific categories of physical function. I think it is advisable, and it is recommended in other elderly population groups and other cardiorespiratory disease groups, that when you assess physical function a range of physical function assessment tools should be used using objective and subjective tools whenever possible.

But why do we actually need to measure physical function in CKD people? Adequate physical function is important for independent living and for disability free living as indicated by the Nagi model as well. But adequate physical function may also be important for other health related outcomes such as morbidity, quality of life and ultimately survival. A causal relationship between physical function and fitness and all these other health related outcomes has been established in the general population and in other cardio metabolic disease states. So what remains to be established now is whether these sort of causal relationships are also seen in the CKD population and whether all these components can be positively infuenced by inteventions that aim to improve physical function.

Indeed the first studies that started to look at the impact or the relationship of physical activity in fitness generally in the CKD population appeared in the literature about 10-12 years ago by De Oreo et al.
But more recently a couple of studies have identified for example, by means of a simple questionnaire, that dialysis patients who reported to be more active on a more regular basis had a significant survival advantage compared to dialysis patients who reported to be sedentary. Stack et al also performed a more detailed analysis and also identified that patients who were able to actually sustain activities of moderate to vigorous intensity on a regular basis also had a more significant survival advantage compared to people who were experiencing severe limitations in these types of tasks.

So what does that mean? It probably means that people who engage in more habitual physical activity at higher levels of intensity have better cardiorespiratory fitness. Sietsema et al tried to investigate whether cardiorespiratory fitness is also linked to a survival benefit. Indeed Sietsema et al identified that in a group of dialysis patients who had peak oxygen uptake determined, they reported that patients with a VO2 peak higher than 17.5 ml of oxygen per kg per min also had a significant survival benefit over a 3.5 year period. The study by Sietsema et al. reported a baseline physiological capacity threshold beyond which a significant health outcome is observed.

Another physiological parameter/ impairment that has been identified in dialysis patients, as you all know, is loss of muscle mass and function. Simple measurements that actually reflect qualitative and quantitative quality of muscle may be associated or can be used as prognostic indicators of survival. Stenvinkel et al attempted to determine whether a simple measurement of strength, isometric handgrip strength, was related to survival outcome. And indeed, in a subgroup of people, of male patients close to dialysis, people with a handgrip strength measurement above the median group value, also had a significant survival advantage compared to people with a handgrip strength value less than the group median.

Even self-reported functional status has been linked significantly with survival and morbidity outcome in the CKD population. Self-reported functional status as calculated using the physical component score from the SF-36 questionnaire has been linked to important outcomes. For example a 10 point decrease in the physical component score has been linked to a 25% increased risk of death and also a 15% increased risk of hospitalisation. But more importantly, Mapes et al also identified, that patients who were classified in the lower quartile of physical function according to the physical component score had a 93% increased risk of dying and a 56% increased risk of hospitalisation compared to the people who had a physical component score higher than 46.

So, it becomes apparent that physiologic impairment and functional status/self-reported functional status have been linked to important and significant survival and morbidity outcomes in the CKD population. Functional capacity, unfortunately, as assessed by means of simple functional capacity tests have not been evaluated or researched in this respect.
In UK we attempted to comprehensively characterise physical dysfunction in the CKD population using a wide range of physical function assessment tools. From objective and physiological testing to simple self-reported and functional capacity testing. What we found, is that simple functional capacity tests like the ability to stand up from a chair or to climb up stairs or to go down stairs for example, revealed significantly larger deficits in functional capacity and therefore functional limitations compared to what was revealed by just using physiological testing for example, or self reported testing, as you see on this slide. So, for example, going down a flight of stairs and stair climbing revealed deficits of about 77% and 102% compared to a healthy control group that was age, gender and physical activity matched. This indicates to me, that simple functional capacity tests like this, can be used or should be used as they may be more sensitive in distinguishing different levels of functioning, or may be more sensitive indicators of functional muscle quantity/quality and functional limitations. However, they need to be evaluated first in terms of their prognostic utility for morbidity and mortality outcomes in the CKD population.

It seems that physical function assessment is important in comprehensively characterising physical health status and identifying patients who may be at risk of worse future health outcomes.
The problem of course here now is that there is a range of different tests reporetd in the literature and from a practical point of view the question is what sort of assessment is the best or the most significant or meaningful to use in the CKD population? When you assess people how do you actually evaluate and how do you characterise physical function?

There are a number of criteria/factots I think to consider here. A number of practical criteria and scientific criteria. I think the main factor that should determine your decision making process in what sort of test to use, whether it’s going to be an objective physiological testing or subjective or functional capacity testing, is the primary purpose of assessment.
For example, if your physical functional assessment is part of a research study with the aim to identify mechanisms of change in physical function, then I think the most appropriate methodology is to use lab based physiological testing that refers or relates to the specific body system of interest. If, for example, the primary aim of physical function is routine assessment of patients in clinical practice, then, using lab based methodologies that require time, effort, expertise available and so on may not be easily applicable so you may have the option there to go for either some objective measurement of physical function using simple functional capacity tests or even self reported data using questionnaires.
One needs to consider I think some scientific criteria as well, when choosing what sort of test to use; and by scientific criteria we mean whether the tests are clinically meaningful, whether
they are clinically relevant (utility), and whether they’re valid, which means whether they actually measure what they say they aim to measure. Whether they’re reproducible, if for example they produce consistent results no matter how many times you actually use the test.
These scientific criteria can be a very useful tool I think to help you interpret a change in physical function and assess whether the change is meaningful or not.

So how do we assess meaningful change? At the moment there have been a number of different criteria proposed in the literature that have been used in the elderly population and in other chronic conditions.

Three different approaches are currently recommended. The statistical approach for example, uses the or proposes the use of the effect size that is mainly calculated from interventional studies. Effect sizes can be calculated and can be classified as small, moderate or large effect sizes. For example, an effect size of 0.5 or 0.6 is classified as a moderate effect size. Basically the effect size indicates the magnitude of the effectiveness of an intervention. So I think it should be recommended that all intervention studies that use some sort of physical function measurement do calculate and report the effectiveness of the intervention by calculating the effect size.

Another statistical approach is the use of the standard error of measurement or coefficient of variation which is determined by reproducibility studies to establish the minimum meaningful change. Standard error of measurement or coefficient variation relates to the variability that comes with the measurement. Therefore, any change beyond that level is the minimum meaningful change that could be seen. The minimun meaningful change does not necessarily coincide with minimun clinical meaningful change.
Another approach is the anchor approach, that uses predefined clinical standards that usually derive from prospective studies trying to find the association between physical function measures and survival or morbidity outcomes. These pre-defined cut off points can be used to assign individuals in different risk groups.
Finally, with the reference group approach you can assess or you can interpret the results by comparing your patient group with a healthy reference group which is appropriately matched though and by appropriately matched we mean not just gender and age but also physical activity matched.

So for example, in the case of the CKD population, we’ve seen people have reported that a 10 point increase in SF-36 physical component score has been linked to important survival outcomes. Therefore, you can use this as a cut off point to determine whether your intervention is meaningful or has a meaningful effect or not. Sietsema has identified that a baseline threshold point that indicates that patients, for example, with a VO2 higher than 18ml/kg/min also have a significant survival benefit. Therefore you can use this cut off point to determine whether your patients have at least achieved this level in studies that aim to improve physical function.
Another criterion that you can use that has not been validated in the CKD population but in the general population is a change in VO2 peak of more than 1 MET and by 1MET corresponds to a level of 3.5 ml of oxygen/kg/min and this change in VO2 peak has been related to a 12% reduction in all cause mortality in the general population.
Therefore, you can use these criteria to define whether an intervention is meaningful or not and the standard error measurement or coefficient of variation of the physical function outcome that you chose to use.

In the following slides therefore, I’m going to give you a brief overview of what I think, people who are interested in physical function assessment should consider, the type of tests that I think are valid enough, reliable enough and meet most of the criteria that should be used in the physical function assessment in CKD patients.

I’ll start with physiological functional capacity and therefore, determining the level of impairment.

As you probably know, VO2 peak is the most widely reported index in the literature. There are published established cut off criteria, reproducibility information and relevant to the CKD population and therefore, I think in terms of characterising impairment at cardiorespiratory level VO2 peak is the index to go for.
Of course you would need direct assessment of VO2 peak using gas exchange during an incremental test. I know that most of the time in clinical practice this sort of assessment may not be possible or feasible but if you the staff and the equipment, I think this is the type of index that should be reported.

Muscular fitness has also been associated with important significant outcomes in patients, in people with renal disease. A number of different indices have been reported in the literature but I think the ones that should be used from now on, that mostly relate to functional ability is assessment of dynamic muscle strength, rate of force development or muscle endurance.
Isometric handgrip has also been reported and has also been used as a prognostic or has been reported to be a significant prognostic indicator of survival but only in male CKD people. Recommended protocols, evaluation criteria do exist in terms of reproducibility. You can compare or you can assess the effectiveness of interventions by comparing patient data against healthy reference values, but unfortunately, there are no clinical cut off points established at the moment in the CKD population. Maybe that’s something that needs to be researched further in the future.

Functional capacity evaluation, I think is the area that is under-utilised and under researched in the CKD population. It offers the possibility to objectively measure physical function free from any difficulties or risks that may come with physiological testing. Free from any inacurracies that may come with self-reporting data and differences in attitudes of people reporting limitations and physical activity. Therefore, it is recommended that we try and establish its clinical utility as a prognostic indicator in the CKD population.

A number of different functional capacity tests are reported in the literature. Some of them have already been used in CKD patients, some others, like the static balance have not. in But static balance tests have been widely used in the elderly population and other cardiorespiratory disease states and they have been identified as prognostic indicators of many important health outcomes and more importantly for falls prevention.
Different types, threshold performance tests, I think may be a more relevant for the older more comorbid individuals, timed performance and especially the single leg balance test has the most discriminatory value in identifying people at increased risk in the elderly population, but not in the CKD.
Recommendations: more research is needed in this area to establish the utility and validity of these tests in the CKD population.

This is my favourite test, a sit to stand test that assesses dynamic muscle strength and muscular endurance. This test as I showed you in an earlier slide at the beginning may have the capacity to discriminate different physical function levels in CKD people as it did reveal greater deficits in functional capacity in the more elderly cohort.

Reproducibility information does exist, relevant to the CKD population, as reported in the studies shown there. The sit-to stand 5, or the sit-to-stand 10 version, measures how fast can you get up from your chair 5 times or 10 times and is considered an index of muscle power. Another very important test that can be used as an indication of muscle endurance is the sit-to-stand 60. Again reproducibility information does exist.
It remains to be established I think in the CKD population, the utility, prognostic value of this test and that’s another area for further research in the future.

Walking performance, is a very important outcome and highly relevant to daily activities. A number of different tests again have been reported even in the CKD population, like the 6 minute walk test, gait speed, timed up and go but unfortunately we don’t have any established criteria, validity or reproducibility or utility criteria relevant to the CKD population. However,we do have some information regarding what meaningful change is, as established from the elderly population and from other patients with cardio metabolic disease.
So for example, studies in the literature using exercise interventions in the CKD population, report changes in the 6 minute walk test of 40-50 metres. But as you see here the clinically meaningful change that has been reported, we need an improvement of more than 71 m or less than 37 m to claim that, that change actually does translate into a clinically meaningful change. In other words the change of 40-50 metres that has been observed in CKD patients is not likely to translate into any meaningful longer term health outcomes.

For Gait speed a change of more than 0.10 m per second is clinically important.
For timed up and go, If it takes more than 14 seconds to complete the task, that’s associated with an increased risk for falls.
Again evaluation criteria need to be confirmed in the CKD population.

Combination tasks I think are great because they stress the body on many different levels. This is a walk test that was developed in the UK, the North Staffordshire Royal Infirmary wal. It combines assessment of Gait speed and dynamic balance and strength. The validity and reproducibility of the test has been tested and reported in the literature and as we mentioned earlier, it has the ability, is sensitive enough to discriminate between different functional levels in the CKD population. An additional benefit, is that this test has been validated against an incremental test using direct gas exchange for VO2 peak determination. This means that if you don’t have the capacity or the facilities or the staff or the equipment to measure cardiorespiratory fitness directly by determining VO2 peak you can use this test as a way to predict or estimate VO2 peak.
The prediction error of this test has been calculated as 11%, so therefore you can predict VO2 peak from that test with an error of about 1.9 ml/kg/min which I think is great.

As I said, these combination tests are my favourite because they stress the body on different levels. They seem to be sensitive enough because they can discriminate between different levels of functional limitations and they seem to be responsive as indicated by this graph.
Following exercise based rehabilitation these performance based tests seemed to normilise as compared to a healthy reference group. Sit-to-stand performance actually dropped down to 3% which is reported to be within the associated standard error of measurement. Overal Walking –strength/balance performance deficits also signficantly reduced compared to healthy reference values.

Who and when should you test? The current consensus in the literature is that every CKD patient should be tested by using either objective or subjective forms of assessment. Consider absolute and relative contraindications. What you need to keep in mind is physical function assessment needs to be repeated at regular intervals in order to be able to define and characterise physical function and deterioration and risk progression.

So general conclusions, based on my own personal evaluation of the literature it seems that physical function outcomes that have been reported are inconsistent and varied across studies. Therefore pooling information from different studies is quite difficult and invalid because everybody uses a different test, everybody uses a different protocol and therefore characterising physical dysfunction just by gathering information from different studies is not possible. At the moment in the CKD population there is no consensus of what is the most meaningful functional capacity measurement. Therefore, a lot of work I think is still needed in this area to establish prognostic value and utility of selected functional capacity tests for future health outcomes. Some functional capacity indices like the ones that combine, the combination tasks, seem to be more sensitive and more responsive.

Finally in summary, what we can say, based on the limited information that we currently have, is that physical function does offer some potential; offers some potential as prognostic indicators but there is a lot of work that still needs to be done especially in the area of establishing the utility and the clinical importance of physical function assessment and especially functional capacity assessment. We also need to establish well-defined criteria that are relevant to the patients and can actually help us to predict disease progression or risk progression.
Also, a very important task I think is that we need to standardise physical function assessment in the CKD population and also standardise the evaluation cut-off criteria and reporting of data.