Kidney Function, Creatinine and Cystatin C

[John_Hemming]

I was unclear as to what meaning particular Cystatin C values had so I started rummaging around and found this paper:

Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and...

Putting aside the issue that Cystatin C does not vary that much depending on race or sex, the fact is that creatinine values are really unreliable because they metabolise in the blood and very often there is a delay between giving a sample and the test being performed.

In reading the supplementary tables for the above paper I found these two figures which I think people will find helpful.

It could be taken to give a biological age of Kidney function based upon Cystatin C or Creatinine.

In the end it is best to see the direction of travel of biomarkers and not to obsess too much about any one value. However, it is helpful to understand what the values tend to be.

[Joseph]

FWIW

This was post two days ago on 03/18/2023

New European Cystatin C Equation for eGFR May Be More Accurate

[John_Hemming]

That’s true, but if you follow that link you will take a while (and a good few links) in finding the above chart. In fact you might not find it.

I was initially interested in working out the actual formula for eGFR and those are available in the supplementary appendix to the main paper. However, in the end it is best knowing what the value of Cystatin C points to in terms of kidney health. I am myself not sure that adjusting for age is strictly right in terms of assessing kidney health even if it gives some correlation with measured GFR values.

Hence I have not actually coded up the eGFR calculation and have decided not to worry about this. I am going by the idea that for men the median value of Cystatin C up to age 50 is 0.86 and then it goes up in a reasonably linear manner.

I am unhappy with Creatinine because of the unreliability of some labs in measuring it. In umol/L I have had figures from about 62 through to 122 in the past calendar year. I only have two Cystatin C measurements November at 0.98 and Feb 23 at 0.89.

[Davin8r]

Peter Attia mentioned in his most recent podcast that his practice has essentially abandoned creatinine-based eGFR and that he only uses cystatin C eGFR now due to its advantages. In an earlier podcast he said they’d been using kind of an average of both.

[AlexKChen]

PSA, because this has now happened to me and at least one other person I know:

If you take creatine supplements, and a blood test shows you have high creatinine levels or low eGFR, this can be because of the creatine, and your kidneys could be totally fine! Your doctor might not know this or be accounting for it, even if you mentioned it to them!

[LukeMV]

I just had my Cystatin C tested and it was 0.65 (range 0.60-1.0 mg/dl) so I was pleased.

[DrFraser]

For longevity and organ age, it would seem like Cystatin C is sensible. For the rapid medical decisions made at point of care eGFR based on Age, Race, Gender and Creatinine will remain the current standard.

The decisions I make around use of IV contrast for example is currently based on eGFR - albeit, a much overstated issue - but that is what I’m stuck with right now as an ER Physician.

On this platform we are much more interested in organ age and either stabilizing or improving things. In that situation, I’d go with Cystatin C … and AlexKChen is indeed correct, creatine supplementation will increase your creatinine and give you worse results. Incidentally, creatine is something I use and recommend to my patients as I think, in general, low risk and modest benefit, but only if exercising, more with weight bearing exercise, and possibly some benefit for sarcopenia.

Sadly not everything is fixed with taking supplements.

However, the focus of this forum - Rapamycin, looks really good for renal function and slowing organ deterioration. Sadly, we’ll all be deceased by the time any type of quality study is generated showing whether this is indeed correct or not. So it is risk:benefit assessment for everyone. Very interesting in taking you life in your hands, and hoping you get it right.

I enjoy smart people examining the literature and sorting out what they actually do in their lives vs. the range of possible.

Excellent forum! I’m enjoying being a new member.

[John_Hemming]

I have been doing weekly blood tests now since about May last year. I became concerned about the reliability of creatinine so I sent a sample taken with the same needle to two different labs. I had 122 from one lab (UK units) and 85.64 from the other.

Only one of the labs I use ordinarily does Cystatin-C, but although it has improved a bit it does not move around as much as creatinine.

There are online formulae which calculate eGFR using only Cystatin-C. On the other hand a nephrologist I know said she really did not like Cystatin-C.

[adriank]

I know kidney function is very important but I’m struggling to understand what the results mean. I mean it is normal according to my doctor. Can someone tell me what I’m looking for while on rapamycin? Thx

[John_Hemming]

That looks mainly ok, but you are not measuring cystatin-c.

[Barnabas]

Picture a bathtub. Water drains at certain rate. Water enters at a certain rate.

eGFR is estimated glomerular filtration rate. How well your kidney is filtering—or how fast the water is training from the tub. The water level is the measured serum creatinine or serum cystatin c.

Creatinine is useless if you are very muscular, because if you are very muscular you have more creatinine entering your blood. It’s like having water entering the tub at a higher rate. So measuring the water level assuming a population average inflow rate means you get a bad estimate of the outflow rate (eGFR).

Apparently cystatin c has the same problem for people with a lot of body fat.

As a very muscular person, I have freaked out my doctor consistently about my kidney function an until I learned all this and explained it all to her.

[As an aside, if you ever take up endurance training and overdo it – like I did going from couch potato to running 40-50 miles per week in a couple months – you’ll have the same issue with elevated AST and ALT, and your doctor might do what mine did and send you for a liver ultrasound if they don’t know you are exercising big time, because these chemicals are released by tortured muscles as well as tortured livers.]

[amuser]

My cystatin C Journey

In June of 2023, and January 2024, I did two tests at LabCorp. The results that came back looked quite good, especially since ceatinine-based EGFR showed 25-30 units less.

I tested again last September, and the results showed a seemingly significant 8-9 point decline.

Not thrilled paying $80+ a pop, but then somebody pointed out you can get $40 (really $60) tests done via Jason Health and Quest, who can pass up such a bargain, so I got another at the end of December.

The EGFR result came back 12 points lower than September. I’d lost about 20 points in a year and a half.

WTAF. Yet one more time, stop most all meds and see if that arrests the decline.

I did three more tests (at least I found a way to get them done at $25 per), two weeks apart, all at LabCorp. Egfrs from those three: 72, then 82, then 102. Apparently my kidney function returned to the status of an eighteen-year-old’s, just by stopping meds.

One odd thing about that last (102) EGFR. Whereas all the preceding tests had been sent to a lab in North Carolina for processing, this one was processed here in San Diego. A new capability apparently.

Just for s&g, tested again, two days after the 102, at Quest. Came back 27 points lower.

All summed up below.

How do the LabCorp and Quest methodologies differ?

LabCorp’s test description says it uses a turbidometric assay, Quest says it uses a ‘particle-enhanced’ TIA.

Maybe the above explains why the Quest results are ‘somewhat’ lower than LabCorp’s. Nothing explains the 102 reading except some malfunction.

Next time I test, I will do cysC at a colocated site, with both blood draws occurring within about an hour. I have read that cysC is affected by hydration status (as is creatinine) so will make sure to be well-hydrated.

[John_Hemming]

I am trying to work out what Cystatin-C is affected by. However, I get it done by one particular lab that includes it as part of their general panel. Another lab will do this as part of a more expensive panel. However, they stopped doing it (they said they ran out of the testing sets) just at the time I started testing mechanisms of control on Cystatin-C. They only started again with the last test they did.

I have found Cystatin-C and Creatinine going in different directions (both ways). I don’t think you necessarily can read too much into movements as they are both affected by quite a few things.

[amuser]

Update:

Two blood draws, one at Labcorp, and one at Quest, forty-five minutes apart. Results:

LabCorp 30% higher than Quest.

The three tests I did at Quest since Christmas have given results of 66, 75, and 70.

Four tests at Labcorp: 72, 82, (lab change) 102, and 92.

That’s nuts. Quest, for what ever reason, far more credible than LabCorp. But if you want results, choose LabCorp.

[John_Hemming]

There is an issue with the formula used as well as the blood test. Hence you need to start with the actual blood biomarker.

Creatinine is dreadfully variable for lots of reasons including metabolising in the drawn sample.

I don’t know enough yet about Cystatin C.

[LukeMV]

That’s absolutely insane. Thanks for sharing.

A little confused though. Are those numbers just eGFR? I’m thrown off by the fact it says cystatin c and creatinine at the top

[John_Hemming]

eGFR can be calculated in lots of ways.

[amuser]

For simplicity sake, I just posted the derived egfrs.

Egfr comparability reported by LabCorp and Quest is easliy verified. They’re using the same equations.

LabCorp cystatin c:

Quest cystatin c:

LabCorp creatinine:

Quest creatinine:

[John_Hemming]

A couple of years ago I had a single needle in my vein and sent two samples to two separate labs which gave me wildly different levels of creatinine.

A problem with blood markers is that some of them are really dynamic. At the moment I am wearing a CGM which at least gives some idea of what is happening with glucose. A static variable from any one point in the day is hard to learn anything from.

[amuser]

Why is there a bot replying to my posts?