Speaker: Brandon Kistler PhD RD
This is a summary of a presentation I attended at the National Kidney Foundation Spring Clinical Meeting on April 11, 2025.
What is protein-energy wasting?
Is a term that refers to reduced protein and energy stores. These reductions are not explained by reduced intake alone.
There are four categories/criteria for diagnosis:
- Serum chemisty
- Body Mass
- Muscle Mass
- Reduced oral intake
3 of the 4 criteria should be met, should be measured more than once.
How prevalent is PEW?
By Stage 3-5 CKD estimates range 11-55%, with most studies reporting around 20%.
In dialysis, maintanence of HD, there is a large variability in reported estimates, the best estimate is 28-54%.
What is a use for PEW?
It can be used to predict patient outcomes. PEW can predict mortality. As PEW worsens, survival also worses. Overtime if you improve PEW survival improves.
What is the mechanism of PEW?
It is multifactorial. A few factors include:
- Increased production of cytokines
- Disrupted endocrine function
- Reduced oral intake.
But do we still need the term? Is it unique to CKD?
There are differences in PEW between cachexia by physiology and mechanistically. Which suggests this is a unique condition specific to CKD.
HD removes toxins and saves people lives. But a key problem is that HD can’t distinguish between what we want to remove and what we want to keep. HD can result in significant protein losses.
Additional HD is a catabolic stimulus. In the basal state (prior to HD) there is increased catabolism both during HD and after dialysis.
What interventions can prevent or treat PEW?
Three broad categories:
- Dietary intake
- Exercise
- Altering metabolic/neurohormonal axis
What nutrition therapies can be used?
Intradialytic window is a common target for interventions. Evidence is clear that many HD patients don’t meet their energy requirments on both their non-treatment and treatment days. This is worse for people who don’t eat during dialysis.
What studies have been done:
- In a study that provided an incentre meal program, the average intake went up when meals were provided during HD. The greatest improvement in dietary intake was for those who were malnourished.
- In another study, the attempted to prevent HD-associated catabolism but providing Nepro during treatments or IDPN (intra-dialytic parental nutrition). In this study they could prevent catabolic state by providing these interventions, though food appear to be better associated with anabolism post session.
- Providing food during treatments is association with improved attendance at treatments. It is possibly related to improved patient satisfaction and reduced discomfort.
Provided intradialytic nutrition (ONS) is associated with significant reductions in mortality. These findings were even better for people with malnutrition.
So if the evidence is so clear, is everyone doing it?
No. Around the world every other geographic aside from North America encourages eating during HD. Data from the US suggests that about 30% of dialysis clinics restrict eating during dialysis.
So what evidence supports restricting eating during HD?
Advantages
- Mortality
- Nutrition
- Adherence and satisfaction
- Education
Disadvantages
- Post prandial hypotension
- GI symptoms
- Reduced treatment efficiency
- Spills or pests
- Choking
- Infection control.
Studies suggests that post-prandial hypotension is the most common impact of eating during dialysis. This effect may last 30-60 minutes.
However other studies have reported that the frequency of hypotension doesn’t increase when people are provided foods. However one key issue is that it depends on how hypotension is defined.
So how can we advance this practice in an era of precision nutrition?
Consider that individual characteristics may influence whether or not someone will experience hypotension.
Characteristics of the meals and food offered likely impact outcomes including:
- Larger meals increase changes
- Largest drop in BP with simple CHOs
- Food temperature also appears to impact.
There may also be patient specific factors, as mean changes can lose the effect that different patients may respond differently to different treatments.
What about protein?
High protein intake is associated with increase hyperfiltration in the kidney. Low protein diets reduced intra-glomerular pressure, and may help reduce uremic toxin production.
So what happens if you change protein intake the healthy population?
Studies suggest there is minimal effect, kidney function didn’t change.
However in CKD, LPD have been recommended since atleast the 1940s. In 2020 KDOQI recommended protein restrictions.
LPD diets have changed over the years when translated into foods:
Kempner diet
- White rice
- Fruit
- Fruit juice
- Sugar
- Limited dairy
Borst Diet
- Boiled potatoes rice
- Custard powder
- Cream
- Butter
- Sugar
- Appleas or pears
- Vegetables
- Cocoa powder
- Tea
- Coffee
50% HBV Proteins
- Were high fat diets
Currently – we are seeing a more plant based diet (PLADO) to achieve a LPD.
What happens when we prescribe low protein diets (LPD) to people with CKD?
In a study that started in 1983, people stuggled to achieve their prescribed protein restrictions. As such the results failed to find significant results. However when results were stratified by eGFR those with middle eGFR showed benefit.
In the late 1990s, another study examined low protein diets. Again these groups struggled to get to their protein targets and there was not much separation between the groups. The results suggested a modest slowing in eGFR decline.
Another study, found no difference between outcomes.
In a 2020 Cochrane review, the review did not find a significant reduction in death or ESRD.
What are key LPD methodological considerations?
There are several challenges in understanding this literature. For example:
- Is kidney filtration measured or estimated?
- Did they account for temporary increases in GFR after eating high protein
- Adherance to LPD is challenging
- Study samples aren’t reflective of the CKD population
- Inconsistency in body weight used to determine protein and energy needs (e.g. IBW vs ABW to calculate protein prescriptions)
- Significant changes in practice (e.g meds!) that have changed since these studies were conducted
So is it time to move away from LPD? Are these diets causing PEW?
Trials have suggested that LPD may exacerbate PEW as LPD can make it very difficult to continue to achieve adequate energy intake. One study found a 600kcal reduction when switching to a LPD, this was associated with reductions in body weight.
This suggests how important it is to have a trained RD to implement diets and to be able to offer routine follow up for these patients.
But how available are renal nutrition resources?
Many countries don’t have access to renal dietitians. Less than 1% of people eligible for medical nutrition therapy for renal nutrition in the US have filed this expense claim. Barriers include limited referrals and even though it is covered, the rates of what is covered is poor.
Do new medications make LPD redundant?
We don’t know yet. In the last several years, SGLT2i have changed outcomes for CKD. The mechanism for SGLT2s overlaps with the mechanism with LPD. However one study suggested that results were synergistic.
What about protein source?
Changes in recommendations from HBV to plant based has also changed. Little is known about how this translation of recommendations impact our understanding.
Questions from the Audience
How can reconcile the 2020 KDIQO guidelines with 2024 KDIGO regarding low protein? (In that the 2020 guidelines recommended lower protein than the 2024)?
One of the key things is that KDIGO suggested more liberal recommendations because the more strict recommendations were too hard to implement. However, this ignores some patient specific factors where there may be some patients who can and want to do this. Additionally, in other parts of the world, some countries do implement this successfully. We also have global resources with the internet that can enable better information sharing that may make this diet more achievable for more people.
We are likely heading to a more nuanced view of proteins. Consider that different amino acids can be considered as unique nutrients, with their own metabolisms. The speaker suspects that individual amino acids are likely to be considered separately from just thinking about “protein”.
With regards to keto-analogues, which are hard to get in North America, they are still available in other parts of the world. We also have opportunities to make better keto-analogues.
How do we reconcile protein restrictions with maintaining both muscle mass and muscle function?
One key challenge is how to measure body composition and function. There is overlap between different terms such as cachexia, PEW, sarcopenia and frailty. One proposed questions is can increasing protein cause to increase turnover of muscle cells? We don’t really know.
We can assess function with handgrip strength and other physical performance tests (see this amazing talk I went to here – if you want to know more about that). However this isn’t consistently done in practice.
Why are other countries having better success with implementing LPD? Do we need to count protein from plant proteins as strictly as animal proteins – could protein goals be higher if the protein source is plant?
Protein needs can be moduled based on individual amino acids. Plant based diets shift targets for what foods you need to consume to get adequate amino acids. However there are various barriers to achieving LPD even with plants. For example fruits and vegetables spoil more readily than other foods, factors could also include how clinicians implement and are they using good nutrition literacy techniques – Dr Kistler made a shout here to Kelly Lambert.
As for red meat, Dr. Kistler, has an upcoming study looking at different types of protein and how it impacts outcomes.
What future products are you working on?
One future study is looking at inpatient diets and better nutrition support for hospitalized patients. Dr. Kistler mentioned a previous study were aggressive nutrition support appeared to disproportionately benefited CKD patients, which may suggest that this population is having a harder time eating in hospital, perhaps related to hospital diets.
Why would simple CHOs cause post prandial hypotension during HD?
The hypothesis is an insulin effect that cause vaso-dilation. There are likely other vaso-dilator hormones involved in this component. Though the mechanism is complex.
