Do not trust an 'eGFR of 90' in bedridden elderly patients. The real reason pharmacists want 'Cystatin C'

This article is written for
young medical professionals (especially pharmacists) who feel that 'evaluating renal function is a bit of a weak point'.

▶Chapter 1: That night, the patient shouted, 'I see children'

The consultation from my junior colleague came the day after the prescription started.

When I asked about the situation, they said the patient had been acting strange since last night.

'There are children over there.'

One moment they would suddenly say that, and the next they would scream.
And this was an 80-year-old man.

He was a bedridden patient with sequelae from a cerebral hemorrhage.
He had developed shingles, and
two days had passed since valacyclovir was prescribed.

I immediately had a hunch.

'I did,' my junior said.
They had even calculated the individual eGFR from the creatinine.
There were no issues with the calculation method or the results obtained.

But I had a bad feeling.

This patient was clearly emaciated.
Being bedridden after a cerebral hemorrhage, he should have had almost no muscle mass left.

The creatinine level was 0.45 mg/dL. The eGFR was around 90.
Looking only at the numbers, his renal function was normal.

But was this patient's kidneys really doing the work of '90'?

I reported it to the attending physician along with my junior colleague.
The attending physician was about to add a medication to suppress the psychiatric symptoms.

The valacyclovir was discontinued.
Two days later, the patient's mental state recovered.

My junior colleague wasn't wrong.
They even calculated the individual eGFR. That is the correct procedure.

The problem is that the number used for the calculation, 'creatinine',
did not accurately reflect this patient's renal function.

So, why does creatinine lie?

▶ Chapter 2: Why numbers lie—A story about muscles and 'waste products'

What is creatinine?

In a word, it is the 'waste product' produced when muscles move.

Muscles use energy to contract.
At that time, a substance called creatine phosphate is broken down,
eventually becoming creatinine.
Since creatinine is a waste product unnecessary to the body,
it is filtered by the kidneys and excreted as urine.

Therefore, if you measure the creatinine concentration in the blood,
you can tell how much waste the kidneys are processing
—that is the reason creatinine is used as an indicator of renal function.

The logic is sound.

But if the premise collapses, this logic no longer holds.

The premise is that 'a constant amount of waste is being produced'.

If the factory (muscle) is running, trash (creatinine) is produced.
By looking at the amount of trash, you can tell the processing capacity of the waste treatment plant (kidneys).

But what if the factory has stopped?

No trash is produced in the first place.
No matter how dilapidated the waste treatment plant is,
because there is no trash to process, the trash concentration in the blood remains low.

Misinterpreting this as 'the waste treatment plant is performing well' is
the biggest trap in evaluating creatinine in bedridden elderly patients.

Let's return to the valacyclovir case.

In their 80s, sequelae of cerebral hemorrhage, bedridden.
This patient's muscle mass
must have been far lower than the average for their age group.

The factory had almost stopped.
So no trash was produced.
So the creatinine was low.
So the eGFR appeared high.

It was not that the kidneys were healthy.
It was just that the muscles were not moving.

The individual eGFR calculated by my junior colleague was correct in terms of procedure.
However, no matter how sophisticated the calculation formula is,
if the input numbers do not reflect reality,
the answer will also be unusable in practice.

In a situation where you cannot accurately measure the amount of waste,
you cannot accurately evaluate the performance of a waste treatment plant.

So, what should have been done?

One way is to adopt the stance of
'not trusting the creatinine value as it is'.

Look at the patient before looking at the numbers.

Compare such information with the numbers,
and judge whether 'this number is reliable'.

Another way is to use a different indicator that does not rely on creatinine.

That isCystatin C.

▶ Chapter 3: Is 'entering 0.6 is safe' true? — The limitations of the round-up method

'If creatinine is low, just enter 0.6 and calculate.'

I think many people were taught that.

The round-up method
—a method of estimating renal function by substituting 0.6 mg/dL when the serum creatinine value is less than 0.6 mg/dL.
It has long been used in clinical practice as a correction to prevent the overestimation of renal function when creatinine is excessively low in patients with low muscle mass.

Certainly,it is better than doing nothing.

However, if you stop at the understanding that 'entering 0.6 is safe',
you may overlook something crucial.

The round-up method works in the direction of 'underestimating' renal function.

There are certainly situations where that becomes a safety measure.
Rather than overestimating renal function compared to reality,
underestimating it and reducing the dose lowers the risk of side effects
—that is the line of thinking.

But if you underestimate it too much, then a different problem arises.

It is underdosing.

Dr. Sumio Hirata, a leading expert in renal drug therapy, points this out.
points this out.

Antibiotics don't work.
Antiepileptic drugs don't work.
Pain isn't relieved.
Infections don't heal.

That, too, ends up harming the patient.
After all, the whole point of administering medication is to treat them.

'Reducing the dose doesn't mean it's safe.'
'Evaluate accurately and deliver the necessary amount'
—I believe that is the true essence of dosage design.

Returning to the story of valacyclovir, the problem was the opposite.

Far from rounding up,
by using the creatinine value of 0.45 as is
to calculate eGFR,
renal function was evaluated as significantly higher than it actually was.

As a result, a standard dose of valacyclovir was prescribed.

Valacyclovir is a renally excreted drug.
If a standard dose is administered to a patient with reduced renal function,
the drug accumulates in the body.
The accumulated drug affects the nervous system,
causing psychiatric symptoms and impaired consciousness
—this iswhat is known as valacyclovir encephalopathy.

That night when they shouted, 'There's a child over there,'
was the process of the drug accumulating.

If the round-up method had been used,
it might have been a little better.
But even then, the 'accurate renal function' would still remain unknown.

The round-up method is a stopgap safety measure, not the answer.

So, what is closer to the 'correct answer'?

▶ Chapter 4: An indicator not fooled by muscle—What is Cystatin C?

Cystatin C is produced through a completely different mechanism
than creatinine.

While creatinine is 'muscle waste,'
Cystatin C is a low-molecular-weight proteinproduced at a constant rate from almost all cells in the body,
regardless of muscle mass.

Whether you have a lot of muscle or very little, the production rate remains almost unchanged.
It continues to be produced at the same rate, whether you are bedridden or an athlete.

And, just like creatinine, it is filtered by the renal glomeruli, and
its blood concentration rises when renal function declines.

In other words,“regardless of the size of the factory, a constant amount of waste continues to be produced”. Therefore, it can more accurately reflect the true processing capacity of the waste treatment plant (the kidneys).

There is one more important characteristic of Cystatin C.

Creatinine has a problem known as the 'blind area'.
This is the characteristic that clear abnormalities in creatinine levels
do not easily appear until renal function has declined to about half.

In other words, even if renal function is gradually declining,
creatinine levels remain in the 'normal range' for a long time.

On the other hand, it is said that Cystatin C levels begin to rise once renal function has declined by about 20%.
Even at a stage where creatinine shows 'normal',
Cystatin C may have already captured the change.

In the case of valacyclovir,
at the stage where the eGFR 90 figure appeared,
if Cystatin C had been measured,
—it would likely have shown a different number.

However, Cystatin C is not a panacea.

It is known that Cystatin C rises regardless of renal function
during steroid use or in cases of hyperthyroidism.
Also, for patients where creatinine is already clearly high
and moderate or greater renal function decline has been confirmed,
the significance of additional Cystatin C measurement becomes relatively small.

Cystatin C is most effective in the
“gray zone” that is difficult to read with creatinine
—that is, that area where the numbers are normal but the patient seems suspicious.

So, does measuring Cystatin C solve everything?

It is not that simple.

Pharmacists do not have the authority to order blood tests.
Even if we 'want to measure it,' we have no choice but to request it from the doctor.
Moreover, there are also insurance constraints.

I have had many experiences where I was asked, 'What is Cystatin C?',
and it ended without being measured.

I am now a certified pharmacist in renal disease pharmacotherapy,
and I face prescription design for many patients with declining renal function every day.
But,having specialized qualifications and knowledge and using them in actual clinical practice to get requests approved by doctors are completely different stories

.

“When to request it”
“How to communicate it to get it approved”
“How to act when it cannot be measured”
—I wrote about those specific judgment criteria and how to craft the words in another article.

▶ Conclusion

That night, when the patient shouted, 'I have children!',
the ward was in chaos.

The nurses were busy responding,
and the attending physician was looking for medicine to suppress the excitement.
No one suspected valacyclovir.

Because the numbers were normal.

But the numbers were lying.
Because there was no muscle, there was no waste produced.
The waste treatment plant was dilapidated.

I believe I was able to notice that 'lie'
because I wasn't just looking at the numbers.

A thin physique. A bedridden life. Disuse syndrome after a cerebral hemorrhage.
When I compared the overall picture of such a patient with
the creatinine figure of 0.45,
—my intuition told me, 'This number is strange.'

Numbers are important.

But to read numbers correctly,
you need to look at what lies outside the numbers.

The patient's activity level. Physique. Muscle mass. Prescribed medications.
By synthesizing these things,
continuing to ask, 'Can this number be trusted?'is essential.

I believe that is the true beginning
of renal function assessment as a pharmacist.

Cystatin C is a tool that helps
provide an answer to that question.

Even if you are not good at assessing renal function, you don't need to overthink it.
For even one more healthcare professional to pause and ask, 'Can I trust this number?'
For them to be able to suspect that there might be no muscle even if the numbers are normal.
That alone will surely build up patient safety.

Look at the person before the numbers.

When you pick up a prescription tomorrow,
I would be happy if even one person thinks that way.

[To pharmacists and healthcare professionals fighting on the front lines]
'I understand the necessity of Cystatin C. But how do I request the measurement from a doctor in a clinical setting?'—I have compiled the specific criteria for this judgment and the [inquiry phrases to move doctors] that I actually use in another article.
I am sharing the 'thought process' I acquired through repeated failures in the field. If you are interested, please take a look at it as a weapon for your practice.

*This article is based on personal experience and views. Please make actual clinical decisions based on the situation at each facility and the individual condition of the patient.