> 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.
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.
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.
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.
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.
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”
It would be interesting what this functional reserve is, right? The microbiome perhaps, or intracellular minerals? Some other thing we haven’t even identified?
> 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.)
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.
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.
It’s interesting they make no mention of trying to understand the body’s ability to self-defend and self-heal. That is, it’s possible to get X (e.g., cancer) and the immune system wins the fight (before it’s even detected).
In theory it’s possible the best early treatment is no treatment at all; that there might be such a thing as too-early detection.
This is a well known phenomenon in medicine. It is always carefully considered when making public health decisions regarding e.g. screening programs and intervention best practices.
For example, a PSA test is useful to detect cancer of the prostate, if a male patient has urination problems. But doing general screening for high PSA values in middle aged men is not considered a good idea, because there are too many false positives and it would likely lead to many unnecessary invasive interventions.
It's also why "early detection leads to longer survival" claims in cancer patients has to be treated with quite some care.
Two people develop a fatal cancer at T0. One is diagnosed at T1, the other at T2, both die at T3.
It looks like the first person survived longer with cancer than the second, but they didn't: the interventions had no effect, it's just a statistical artifact.
This is by no means always the case - earlier detected cancer is more treatable - but it still needs to be controlled for.
Have a friend working as urology surgeon - basically all men get prostate cancer, its just a function of time (unless you die young). Most of them is benign, or cause few issues and are often let alone.
If you would run scans on all males above say 45 there would be endless stream of operations happening, all of which would lower quality of life for everybody, and sometimes shorten their lives a bit or a bit more. Any public healthcare system would be brought to the edge of collapse by just this since surgeries are supremely expensive everywhere, that's not just US invention.
True for many things. You can have the HIV virus in your blood, and successfully fight it off, preventing infection. Your immune system will remember, and thereafter show markers that are indicate "possibly infected" - but you will not be CURRENTLY infected.
Number of studies are meaningless by itself, and an intellectually rigorous scientist wouldn't use that as a metric. We've known for decades that any serious infection can have long lasting effects for some patients. There's nothing special about SARS-CoV-2.
To me, this is the strongest argument for a centralised health system, such as the UK NHS.
When you have one organisation responsible for health as a whole rather than just treatment, you can make better decisions. The usual example I give is that it's cheaper to give out the contraceptive pill than deal with pregnancies, but the same thinking applies to broader disease and health.
This holds true for many things. It’s easier to stay in shape and maintain a healthy weight than it is to recover from getting out of shape or overweight. The longer someone spends out of shape or overweight, the harder it becomes to escape the cycle. There’s no better time to start than now.
As for preventative medical treatment: This one is a difficult topic. There’s a popular misconception that getting a lot of different blood tests and imaging scans is a good idea to identify conditions early, but most people don’t understand that these tests (including imagine) are prone to a lot of false positives. Excessive testing has been shown time and time again to lead to unnecessary interventions, leading to worse outcomes on average. A number of previously routine medical tests are now not recommended until later age or until other symptoms appear because routine testing was producing too many unnecessary interventions, producing a net negative benefit.
It’s a hard concept to wrap our heads around when we’re so attached to the idea that more testing means better information. It’s a huge problem in the alternative medicine community where podcast grifters will encourage people to get various tests like organic acid tests or various “levels” testing, then prescribe complex treatment programs with dozens of supplements. The people chasing these tests then throw themselves far out of balance with excess supplements while sinking thousands of dollars into repeat testing
This sounds like an example of a fault in how to take action based on results vice a fault in getting too much data. Perhaps the conclusion you state about the better approach being to forego tests is true. For example, if emotional and legal factors prevent patients and providers from acting rationally here. Optimistically, we can do better.
So exercise, eating healthy, fasting, brushing/flossing teeth, consistent sleep schedule, daily sun exposure, good relationships, and stress management all depend on a health insurance plan?
I think you may be missing the point: preventative treatment is typically much less expensive, for instance behaviour and dietary changes do not require drugs at all and avoiding some conditions can be helped by drugs which have long since come off patents.
But even with your point, all insurance companies I've ever had cover with in the UK have had some element of support for preventing illness (periodic assessments, support material and trackers) and, at least with people covered under company schemes, they clearly have an incentive to offer more if you are at risk of becoming affected by a preventable illness.
And yet not a single doctor in the United States will permit you to care about early signals, preventative medicine, or routine deep dive bloodwork, in order to stave off those diseases. Anyone who's on top of this is paying fully out of pocket for individual tests, screenings, medicines. Manageable for some, unattainable for most.
My ex girlfriend was a doctor and we talked about this once. The gist of it that I got was that excessive early tests have a lot of risk factors that come along with them, because tests themselves being harmful (CT scans cause something like 5% of all cancers), and because false positives lead to unnecessary treatments, surgeries, medications, etc which can cause real harm. Basically, if the expected harm from the proactive testing is greater than the expected harm it would mitigate, you don't do it.
Huh? Plenty of doctors out there cater to the "worried well" and will order any blood work you want or spend a lot of time with you on preventive care. But of course most health insurance plans won't pay for that. In most cases it's a total waste and doesn't significantly improve patient outcomes.
Readit News
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.
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.
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.
Wouldn't be surprised if there was some source of hidden damage like that.
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...
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).
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.)
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.
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.
In theory it’s possible the best early treatment is no treatment at all; that there might be such a thing as too-early detection.
For example, a PSA test is useful to detect cancer of the prostate, if a male patient has urination problems. But doing general screening for high PSA values in middle aged men is not considered a good idea, because there are too many false positives and it would likely lead to many unnecessary invasive interventions.
Two people develop a fatal cancer at T0. One is diagnosed at T1, the other at T2, both die at T3.
It looks like the first person survived longer with cancer than the second, but they didn't: the interventions had no effect, it's just a statistical artifact.
This is by no means always the case - earlier detected cancer is more treatable - but it still needs to be controlled for.
If you would run scans on all males above say 45 there would be endless stream of operations happening, all of which would lower quality of life for everybody, and sometimes shorten their lives a bit or a bit more. Any public healthcare system would be brought to the edge of collapse by just this since surgeries are supremely expensive everywhere, that's not just US invention.
When you have one organisation responsible for health as a whole rather than just treatment, you can make better decisions. The usual example I give is that it's cheaper to give out the contraceptive pill than deal with pregnancies, but the same thinking applies to broader disease and health.
As for preventative medical treatment: This one is a difficult topic. There’s a popular misconception that getting a lot of different blood tests and imaging scans is a good idea to identify conditions early, but most people don’t understand that these tests (including imagine) are prone to a lot of false positives. Excessive testing has been shown time and time again to lead to unnecessary interventions, leading to worse outcomes on average. A number of previously routine medical tests are now not recommended until later age or until other symptoms appear because routine testing was producing too many unnecessary interventions, producing a net negative benefit.
It’s a hard concept to wrap our heads around when we’re so attached to the idea that more testing means better information. It’s a huge problem in the alternative medicine community where podcast grifters will encourage people to get various tests like organic acid tests or various “levels” testing, then prescribe complex treatment programs with dozens of supplements. The people chasing these tests then throw themselves far out of balance with excess supplements while sinking thousands of dollars into repeat testing
Sounds like a misguided incentive ...
But even with your point, all insurance companies I've ever had cover with in the UK have had some element of support for preventing illness (periodic assessments, support material and trackers) and, at least with people covered under company schemes, they clearly have an incentive to offer more if you are at risk of becoming affected by a preventable illness.
there should be more like it. (thanks for the archive link btw!)
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