An unprecedented window into how diseases take hold years before symptoms appear

> What UK Biobank is revealing, scan by scan and layer by layer, is that disease doesn’t arrive out of nowhere. It accumulates quietly, shaped by genes, environment, and habits.

I think that is already known for a while. It's called functional reserve, and was a big topic in HIV patients (and then again for SARS-CoV-2).

Like people with higher cognitive capabilities will be protected by those a bit longer before onset of HIV-associated neurocognitive disorder (or even dementia).

Same for kidneys: They have a functional reserve that you are born with gets used up during life, until it is gone. Acute kidney disease treatment is aimed at preserving whatever little function is left.

A very elderly doctor referred to "cognitive reserve", lamenting hen had more of it when younger.

Functional reserve means you are completely well but the start of the disease is coming closer as the former is depleting.

Another case is when disease starts subtly and slowly _with_ initial symptoms that are otherwise not debilitating. Eg Alzheimer's starting decades ago by being forgetful.

I have no idea which one the post is reffering to.

I am a 61 year old guy. I've never been overweight, never smoked, I've never been drunk and drink only infrequently, and have been fitter than average ... sometimes very fit. A few years ago I decided to make an undirected kidney donation. I thought I'd be a slam dunk. Everything was great, except my eGFR (estimate granular filtration rate) was 73, and for many people it is more like 110, which disqualified me, as after donating my number would get cut in half, putting me at some risk.

So I pulled up blood work results going back 15 years that I had records for and found that 73 was my high score! It typically was mid 60s, with a low of 61. I have no idea why it is so low. Anyway, this is the reason I'm relating this story. It seems odd that my kidney function has gone up. It wasn't just a fluke -- I've had bloodwork done at least five times since then and I'm always in the mid 70s now.

It would be interesting what this functional reserve is, right? The microbiome perhaps, or intracellular minerals? Some other thing we haven’t even identified?

In case of kidneys, my understanding is that only a certain subset of glomerular cells are actively filtrating blood at any given point. The other cells form the functional reserve, and start to become active once the other cells age out, or are disrupted due to an event (like poisoning, such as mycotoxin damage from eating moldy food). Once the functional reserve is exhausted however, no new cells can become active and you are left with whatever dwindling GFR you have, until you get a transplant.

With the vascular system you have example arterial elasticity which is an important measure of vascular health. When your blood vessels become less elastic it does not immediately cause symptoms, but it increases the risk of heart disease and stroke. This is also why periodontitis and gum disease is a predictor for vascular diseases: Bacteria enter the bloodstream through inflamed oral mucosa and form plaques along the blood vessels.

I previously looked at eGFR numbers and they seem very ballpark-ish and prone to fluctuation, as their name implies. My understanding is that they are used to detect acute cases, rather than to give a real measurement of your kidneys if you’re well.

> It would be interesting what this functional reserve is, right?

It is most likely not a single thing.

Looking for "the functional reserve" is like looking for which part of an airplane is the "multiple redundancy". Or which line of code is the "fault tolerance" in google's code base. It is not a single part, it is all the parts working together.

Just looking at the kidney example (which is not the only kind of function we can describe having functional reserve.) functional reserve is that there are two kidneys, and each kidney have multiple renal pyramids, and if this or that part of the kidney functions worse other parts compensate and will work overtime.

Depletion of functional reserve is not something literally running out (like a fuel tank running empty), it is more like a marauding gang shooting computers in a cloud data center. Sure initially all works as it used to, because the system identifies the damaged components and routes the processing to other ones. But if they keep it up they will damage enough that the data center will keel over and can't do what it could do before.

(No, I'm not saying that a human body is literally a data center, or literally an airplane. What I'm saying is that all three shares the common theme that some process is maintained in the presence of faults.)

>"This is also why periodontitis and gum disease is a predictor for vascular diseases: Bacteria enter the bloodstream through inflamed oral mucosa and form plaques along the blood vessels."

And yet in the year 2025 dental care is globally treated as seperate from other healthcare, a strange historical artifact that clings on.

Thankfully biology has redundancy, so a single cosmic bit flip does not send humans into a BSOD.

In biomed sciences we rarely refer to the huge amount of resiliency of living organisms. They are so robust, stable and self healing that it would need a fleet of human made machines to cover the basic difficulties.

Maybe you lost weight or changed some aspects of your diet after 50?

Your diet is less salty maybe?

eGFR is an indirect measurement of kidney function. It can be slightly lower in some people with normal kidney function for various reasons.

There are additional kidney function tests that would be used for a more complete picture of kidney function if it was suspected that you had a kidney condition. There are more direct GFR tests, minus the ‘e’ prefix which means estimated. However, a better blood test that is more accessible would be Cystatin C. Worth getting one of those as a baseline at some point.

In the content of donation, though, it’s not worth risking it. It’s best to play it safe. If you happened to have been inspired by the kidney donation story and blog that circulated in rationalist communities, it’s also worth noting that it was not a great source of information about the relative risks of the procedure, despite being presented as comprehensive and well researched.

Story from the US: had an awful tooth infection (from a known dead tooth) that I tried to ride out, half my face was swollen up, even my eye looked half shut. Well after a day of this I couldn't take the pain. Called my doctor "we don't pull teeth, you have to call a dentist." So I called a dozen dentist and was told either "we aren't taking new patients" or "we can't get you in for 6 months".

I ended up just driving to a dentist and saying "look at my fucking face! Pull this fucking tooth out!" Finally a dentist was able to spare 30 seconds to yank it. Bill was something like $750.

The US is a dystopian hellhole.

Glomerular not granular

I suspect that my kidney function was negatively affected by a reaction to the contrast used in some medical imaging I had a few years ago. Unfortunately, lack of access to healthcare means I've never been able confirm it. I just know that, before that episode, I was noted for my ability to hold my alcohol; after, no more, and I've had to be careful about taking certain kinds of OTC medication because I can feel it affecting me similarly.

Wouldn't be surprised if there was some source of hidden damage like that.

And you couldn’t just board a plane to Mexico or anywhere down south and get the job done for half the price including said flight? People keep complaining but don’t realize that no place is perfect in this world.

What an asinine response.

I got a doctor to pull an internal tooth that had formed a cyst around it, a maxillofacial surgeon.

The dentist quoted $1300 but said insurance wouldn’t cover it, it’d be out of pocket. The surgeon did it (I was awake with local anesthesia) for $300 but insurance paid an additional $4000.

Before all this, A PE owned dentist office (the one that didn’t have the six month wait) had told me two years before that the pain I was experiencing was because I had periodontal disease and that I just needed to get a periodontal cleaning (which cost $750 and didn’t help at all, also conveniently not done by a dentist but a dental hygienist). This turned out to be very dangerous because the cyst was pushing and wearing away at my nose bone, and if I’d waited any longer my nose may have sunk into my face.

It’s definitely maddening the hoops one has to go through to get proper dental care in the US.

Regardless of the financial and administrative issues, dentistry is still far more an art than a science. Go to 10 different dentists for any serious condition and you'll likely receive 10 different treatment plans. In most cases they're making good faith recommendations but there's a huge amount of subjectivity and personal bias involved.

Physicians have recently started embracing evidence-based medicine with documented best practice treatment guidelines so hopefully a similar cultural change will come to dentistry in time.

Some places are significantly worse than all others in the same wealth class though.

Somebody further up quoted such insane numbers - $750 for a proper periodontal cleaning? That's usually ~50 to 80€ in Germany. For a _full_ self payer.

Those prices and the health system creating them are utter insanity.

Mine was low, but it's probably because I was taking creatine. Do you happen to take creatine?

It's inverse of how much is your blood creatinine level, and creatine increased that.

I am early 30s, and my eGFR was below 60 due to creatine (at least I think it was creatine).

Seriously. "Just"

I’m working with doctors at the moment in a similar area. eGFR is well-known to decline at approx 1 point per year after age 30. You’re fine.

Here’s just one source: “After the age of 30 years, glomerular filtration rate (GFR) progressively declines at an average rate of 8 mL/min/1.73 m² per decade.4”

https://www.racgp.org.au/afp/2012/december/ckd-in-the-elderl...

Why though? You demand a service that you can get cheaper abroad. You can’t change the health system but you can travel to a socially developed country that hasn’t yet fallen victim of corruption

Nope, no creatine.

Thanks for the correction ... I should have looked that up instead of going by memory.

What did Scott leave out from the post(s)?

https://www.astralcodexten.com/p/my-left-kidney

https://www.astralcodexten.com/p/highlights-from-the-comment...

The first time I tried a community donation, they didn't do that. But a couple years later one of my brothers needed a kidney, so I got tested again. Again, my eGFR was low 70s, and so they did the Cystatin C test. I scored 1.00 (ref range 0.52-1.23mg/mL) which they mapped to an eGFR of 78, and I was rejected.

None of my other siblings were a good enough match, so one of my sisters donated hers (IIRC, her eGFR was low 90s) as part of a chain. That was more than two years ago and my sister is feeling fine. My brother is no longer on dialysis, though he didn't experience one of those feel-good stories where he got his kidney and he suddenly felt amazing, unfortunately.

[EDIT] I forgot to address the last part of your comment. A few years back an email acquaintance of many years mentioned that he is on dialysis. Although he is in Germany, I said if he can't find a donor, I'd be willing to fly there to donate directly if I matched or to be part of a chain. He is in Germany and his response surprised me: thank you very much, but he said living donations were not allowed (at least from non-relatives). Maybe things have changed, this was back in 2016.

"But there are some reasons that make this solution unlikely. At first I am very sure that this kind of donor isn't allowed in germany. We have strong ethic rules regarding donation by living people because of the bad experiences with commercial organ deals."

Still the idea sat with me. I have donated many gallons of blood and 25 years ago signed up for "be the match" marrow donation that never came to anything, though every few years they send a confirmation letter to make sure my address is still valid. It most charity donations I can write a check and there is a diffuse sense that maybe I incrementally did some good, but giving a kidney has a high probability to make one person's life dramatically better. So that was my motivation.

A same day flight to Mexico is $1000 where I live. Other countries seem to have figured out healthcare. The US can too.

It might be able to, but only after passing legislation to control guns and protect school children from being victims of daily school shootings