MIDDLE AGE AND KIDNEY STONES? WHY NOW?

Middle age 45 – 65, not the usual time to form your first kidney stone. The average for new stone onset is 35, with a spread of about 12 years, so by 45 you might think the odds are in your favor. But not always. Sometimes they start late, even into your fifties or sixties. It doesn’t matter some of the time. A stone is a stone. But older people get stones for a different spectrum of reasons than when young, so you have to think a bit about why.

The image, a self portrait by Jan van Eyck (1390-1441), was painted in 1433 in oil on panel. It hangs in the National Gallery, London.

This article is co-authored by me with Jill, but was her choice of topic. She is sure her patients will love it. I hope so.

Primary Hyperparathyroidism

This is not rare as a cause of stones, and very important. On the one hand, it is a systemic disease. High serum calcium can cause kidney injury, and raise blood pressure. Bone mineral can be lost. On the other hand, it is curable. Although PHPT can occur in youth, the average age of diagnosis in a recent and large VA hospital record review was 67-68. A large Canadian survey of published papers estimates that diagnosis is usually after 50 years old and that, as is well known, women have it more frequently than men. In a large single center report of a university cohort the mean age at diagnosis was 61 years with stones, 69 without stones.

We have already written two articles on how PHPT works, and how it is diagnosed and treated. This one is very clinical. This one is very detailed, all about mechanisms and for the curious. What matters here is that if your stones begin later in life – after 50, for example, this disease needs to be higher on your list than if they begin at 25 or 30. You need to be sure about your serum calcium. You need to be sure it is measured when fasting, and looked at carefully. Even a little elevation should raise an eyebrow and lead to more measurements to be sure. 

Uric Acid Stones

When Do They Occur

This nifty figure from a paper by the Mayo Clinic group shows how age changes stone type. Men are on top. Calcium oxalate stones are always the most common, in both sexes, but under age 30 or so calcium phosphate stones (the open squares) are reasonably common, especially in women.

Uric acid stones, the open diamond, creep up on both sexes, after age 40 in men, and 50 in women, and by the sixties are more common than calcium phosphate stones in either sex.

Uric acid stones occur because the urine pH falls, we know that with perfect certainty. The low pH protonates the uric acid molecule, so it loses its only charged site. Water no longer has a good way to connect with it, so it just leaves the solution as crystals.

Why Does the pH Fall?

We asked ourselves that very question and tried to find out.

Lots of things happen as we get older. We get fat. Our kidneys gradually lose their youthful glow. Both of these can lower the urine pH. We get diabetic, and that surely lowers urine pH. Do any of these account for what this figure shows us?

Urine pH Does Indeed Fall

We were fortunate to come into possession of a large set of laboratory data collected by a national kidney stone testing laboratory. It has no names, but did have age and sex, and urine stone risk factors. So we could reconstruct what happened to urine pH with age in men and women.

In both, men are triangles, urine pH fell very rapidly beginning below age 30, and at all times women had a higher pH than men. We have already written about this feature of women. Eating exactly the same food as men, women extract more alkali from it, so their urine is more alkaline. That is why they form more calcium phosphate stones, as the picture from Mayo Clinic shows.

But something happens to women as they age, and men, too. Whatever it is that makes their urine rather alkaline at the beginning gives way with age, and not so old an age, either. After all, much of the fall is before 50, the early part of so called middle age.

It Is Not The Getting Fatter

We get fatter with age. Everyone knows that. Not everyone does it, but on average we all do. I suppose it is less exercise and too much food, but we are not studying this matter here, now.

Below, you can see body mass index (BMI) rising with age in this very large set of data (nearly 9,000) patient lab

studies. It goes up in men (triangles) and women, and it goes up very rapidly between 33 or younger and 50.

But, if you adjust for the BMI, the urine pH fall is not affected.

The urine pH falls about the same in both sexes. Compare the graph just to your left with the one just above.

By adjusted, we mean we used complex multi-variable models to account for the rise in BMI and the linkage between BMI and urine pH. They are linked, and BMI rises, but the rise is not enough, given the linkage, to explain almost any part of the falling pH. So it is not obesity.

It is Not Loss of Kidney Function

Here is another graph. Kidney function was measured using creatinine clearance, a common measure.

It went down with age.

But, it began to fall after urine pH had already fallen quite a bit. In other words, the one was not correlated with the other very well. Correlation is not causation, but the other way around is true. Things that are not correlated are not often related causally.

A more elegant approach is to do another of the multi-variable analyses, which we did. The graph on the right, just above, shows that urine pH fell more or less the same if you did (as here) or did not (the original graph above) adjust for kidney function. So, it is not BMI and not kidney function.

pH Falls Even Though Alkali Absorption Rises

The reason for the higher urine pH in women is their greater ability to absorb alkali from their diet. So, was it possible that with age people lost some of that ability? Their bodies would have less alkali from food, and their kidneys would have to work harder excreting acid, and make the urine more acid in the process.

What we found was the exact opposite. The absorption of alkali, which is called GI anion for historical reasons, rises with age. It does so in women and in men. When women are younger, they absorb more than men. See how the circles, women, are higher than the triangles. But around 50 or so women and men converge because women are rising slowly, men rapidly.

But all the while, urine pH is falling. That is backward. When we showed you how women act, you could see that with each meal their GI anion rose and their urine pH rose with it. Here, the urine pH is falling despite more alkali.

You might ask what would happen if we used our multi-variable mathematics to remove the effects of the increased GI Anion. How much does it help keep the urine pH from falling even more?

Without The Extra Alkali Urine pH Would Fave Fallen Far More

Here is the calculated effect. Urine pH falls far more and far more steadily, and the sexes are now more or less the same.

We think that the actual losses of kidney function and the rising BMI were always important. But, as these would have tended to make the urine acid, rising GI Anion offset their effects.

If you take it away, admittedly by mere mathematics, you see what would happen if there were no compensation.

Do we really think that somehow the intestines know to raise their absorption of alkali?

Why not?

They have about 10% of all of our neurons, and the brain communicates with the GI tract.

This is all for some future research. But what it tells us is that age itself, for reasons we do not as yet know, lowers urine pH. As a result uric acid stones become far more common, and the phosphate type of stone far less common.

Diabetes and Insulin Resistance

All of the forgoing was a large scale population effect. Within that population were certainly people with diabetes or insulin resistance. They cannot account for what we found because most of the fall in urine pH occurred rather young, at a time when the sheer prevalence of diabetes has not as yet risen so much.

But for many people, particularly those with serious obesity, or simply those over age 50, diabetes and insulin resistance are increasingly common. Both states lower urine pH, a lot, and cause uric acid stones. We have reviewed the main research work on this topic, that was done mainly by our colleagues in Dallas, Texas.

New onset uric acid stones can simply reflect the general age effect. But it may not be that. In the earlier stages of insulin resistance, insulin levels run high and common fasting blood glucose levels remain ‘in the normal range’. Usually they are at the top of the range, and the hemoglobin A1C is too high – 5.9 or more. It is then that one is best off taking steps, like weight loss and major life changes.

You Are Just Late To The Party

Life Has Changed

The onset age for stones may center around 30, but there are those who are slow and wait until later. Perhaps they formed their stones in their 30’s but no one knew. Perhaps they changed something and brought the stone on. Some people begin a busy travel schedule because retired, some take up extreme sports or marathon running to stay young. Some progress at their work and are promoted to a job that requires lots of long distance travel. Lots of people make eating out a time to meet friends and family, because the children are all gone.

You might think this has no special significance, but it may.

More than eating out, people change their diets in mid-life, to be healthier. But the changes may not always be healthy. Fad diet are always like the butler in a murder mystery: present at the scene, and capable of almost anything.

Your Genetic Hypercalciuria Was Unnoticed

If you had genetic hypercalciuria, you would not have known about it. So new stones mean that you need to check for that problem, and also for bone disease.

For men, the association between stones and bone disease is very well documented. For women, at least in a large epidemiological study, a history of stones and finding of reduced bone mineral were not linked. But whether they might be through genetic hypercalciuria could not be ascertained because no urine testing was available.

In studies that specifically focus on stone formers, a link to bone fracture appears far more obvious than in studies that focus on bone mineral loss as a primary aim.

Urine calcium is known to rise with insulin resistance and diabetes. Although we are not convinced about new calcium stone onset, it is enough to mention here that new calcium stones should always lead to at least a brief look at fasting blood glucose.

Drugs

If anyone asked me, I would say Topamax and its many relatives are a common reason for new stones anytime in life. Especially in people with genetic hypercalciuria, new use of calcium supplements can cause stones. There are so many more possibilities we can just say that with new stones you need to review all of your meds and supplements, perhaps especially the latter. Maybe change your diet and stop the Tums for esophageal reflux.

What Does This Mean For You?

New stones in midlife or later mean they must be analysed. This is absolute. Otherwise how can you be sure about uric acid? Primary hyperparathyroidism produces calcium phosphate and calcium oxalate stones. We have always advocated for analysis of every stone, and in later years that maxim is more important than ever. New ones are a worry. But established stone formers can change from calcium to uric acid.

Apart from stone analysis, be sure your fasting blood calcium is truly normal. We mean by this not only within limits but a bit below the very top, because PHPT can raise blood calcium very slightly yet be there and a serious disease. If it is even suspicious, we have already written out what we do, which is to get many more fasting morning bloods for calcium, and with time things will become clear.

Think about your bones and your drugs, and how your life has changed. Think about blood glucose and be sure it is normal.

At the end, you may simply be a late comer. If so, treatment is as it is for everyone. But if not, a serious inquiry may give you real benefits.

 

23 Responses to “MIDDLE AGE AND KIDNEY STONES? WHY NOW?”

  1. tastowell

    I am a 55 year old female. I had kidney stones issues that first became apparent at age 54 (Spring of 2018). I’ve had lithotripsy on two stones since then. I’m told one remains. I have had a Litholink analysis done, but I don’t have the results yet.

    In 2002, I had radioactive iodine ablation of my thyroid. In 2017 and up until the first stone symptoms in 2018, I had mild depression and severe panic attacks and anxiety that I had never experienced before. I attributed it to perimenopause, but have since read that anxiety can be a symptom of hyperparathyroid. The last time I had calcium checked was in 2017 and was in the middle of the normal range at that time. As far as I know, I’ve never had parathyroid levels checked. Do you feel that’s something that I should have done? The one time I mentioned it, at the onset of he kidney stone problems, my concern was dismissed because my calcium level was normal.

    Reply
  2. Vincent

    Hi Dr. Coe,

    I am a 31 year old, otherwise healthy, male with a Y shaped ureter on my left side, the only side producing stones. I had two stone analysis done on the pile of fragments I collected after my only lithotripsy done 11 years ago, and they were 60% and 65% calcium phosphate, respectively, with the remainder a mix between calcium oxalate mono and dihydrate. Before this procedure in 2008, there was one stone in each of the lower, mid and upper poles. Fast forward to today and I now have 3 very large ones in the upper pole, 2.4cm, 1.3cm and 1.1cm.

    My urologist suggested to do a lithotripsy and put a uretal stent in so he could do a uteroscopy a few weeks later. I’m curious if you would suggest this approach, or if not, what you might do instead?

    I’m also interested in finding out if there is some type of systemic issue going on that is causing me to form stones. Since I have the duplicated collecting system on the left, and that is the only side with stones, my doctors have always just said that the anatomy is the cause. I have had a bunch of normal serum calciums over the years, some low vitamin D levels, some higher 24hr urine calciums, and for some reason my 24hr urine creatine/kg has always been high, even though I am not overweight.I am already on a low oxalate diet, trying to up my calcium with meals, increasing water intake, and decreasing sodium and sugar. I have been on and off citrate supplements over the years, and am going to begin testing my urine pH while taking them to make sure it doesn’t increase too much. Since the stones are mostly phosphate, do you recommend any adjustments in regards to dietary phosphorous/phosphate? Does dietary phosphorus intake have a significant effect on phosphate supersaturation?

    Thank you in advance for any thoughts you might have, and thank you for all the information on this site, it is incredibly helpful.

    Reply
    • Fredric L Coe

      Hi Vincent, The high urine calcium is the main culprit, and the abnormal urology on the left adds risk by increasing likelihood that crystals will be retained in the kidneys – a two hit model. That the stones had abundant calcium phosphate suggests that possibly the upper pole drains less well than normal and the renal elements thus drained may have lost normal acidification so urine from that segment is more alkaline than the bulk phase urine. Firstly, I would hope that your surgeons have secured the best possible drainage of the upper pole. Then, I would use reduced diet sodium and perhaps thiazide to lower urine calcium as much as possible. I have no idea why potassium citrate would be an ideal choice as we lack trial data for those with abundant stone phosphate content and the agent does raise urine pH. This article parses out the interactions of diet and meds. Of course, your physicians are in charge here, and the only use for my remarks is that they might find them helpful – or not. Regards, Fred Cpe

      Reply
      • Vincent Cilento

        Hi Dr. Coe,

        Thank you so much for your reply. I have a few follow up questions. I know there many, so short/no answers are completely understandable 🙂

        1. “The upper pole drains less well than normal and the renal elements thus drained may have lost normal acidification so urine from that segment is more alkaline than the bulk phase urine” – It seems like their would not be, but is there any way to test any part of this statement?
        2. On securing the best possible drainage of the upper pole – do you mean clearing the stones? If so, do you see any potential issues with the combination of lithotripsy and uteroscopy – or when is nephrolithotomy a better approach? My urologist mentioned a few uteroscopies because of the overall stone burden, and I would like to have as few procedures as possible.
        3. I don’t see anything in your or other articles regarding dietary phosphate – do you think it has a significant enough affect on stone formation to consider dietary change as with oxalate and oxalate stone formers?
        4. Is there any concern here for any endocrine issues? Is supplementing with vitamin D contraindicated for any reason?

        Reply
        • Fredric L Coe

          Hi Vincent, only that stones from the upper pole will have high calcium phosphate content. Ureteroscopy is the best procedure overall, in that PERC, though very definitive, is a more invasive surgery. During URS laser light is used to disrupt the stones. As for diet phosphate, I have no basis for commenting in that it has not per se been linked to stones. Cola drinks have a lot of phosphate and are linked to stone disease, so perhaps by inference one can indict it. The very article you post on concerns primary hyperparathyroidism, the main endocrine issue. Regards, Fred Coe

          Reply
  3. Colleen Turner

    Thank-you for all the education and help your site provides!
    My husband was found to have 5 large stones in 2016 and was also diagnosed with CKD Stage III. Initially we saw a nephrologist for the CKD and our urologist for treatment/prevention of stones, (he removed 2 via sub cutaneous nephrostomy which we had analysed and the others via lithotripsy, we were unable to capture any fragments for analysis.) 6-weeks after removal our urologist started a monitoring and prevention program with us using Litholink testing. After a few months the 2 doctors decided between themselves that the nephrologist would take over and only refer us back if she suspected new stones. As we were newly arrived in the area and somewhat overwhelmed by recent events we just went along with it.

    So far so good – no more stones. But as I have learned more via your site I feel we need a urologist to be monitoring stones and reviewing the supersaturation results with us. The nephrologist has had my husband on Allopurinol since 2016 and gave the reason as the 50% uric acid content of one of the stones. This is contradicted by your articles (only recently read by me) on uric acid stones where you advise that increasing PH above 6 is the way to go and that Allopurinol does nothing. Hubby’s PH was immediately corrected back in 2016 with Potassium Citrate and remains good –

    We live in the North Dallas area. Are you be able to recommend any urologists ? Would greatly appreciate it –
    Kind Regards-Colleen

    Reply
    • Fredric L Coe

      Hi Coleen, Indeed the uric acid portion of his stones require potassium citrate as you note, and the other half, no doubt calcium oxalate monohydrate may require more. You are fortunate in that superb stone experts work in Dallas. I would recommend Dr Peggy Pearle at UT SW in Dallas. She is a brilliant stone surgeon and can take care of everything including prevention. Feel free to use my name, as she is a close friend. Regards, Fred Coe

      Reply
      • Colleen Turner

        Hi Dr Coe,
        Many thanks – we see Dr Pearle next week.
        Re stone analysis – you are correct – the uric acid stone(50%) was 50% calcium oxalate monohydrate. The other stone was 70% calcium oxalate monohydrate, 15% calcium oxalate dihydrate and 15% carbonate apatite.
        We will be discussing all this with Dr Pearle but I have a question:
        – What does it mean if urine pH gradually corrects requiring a steady reduction in Pot Cit dosage?
        Initially (2016 2 LItholink tests)
        urine ph = 5.096 , 4.994
        24Cit = very low at 212 and 145. Potassium Citrate prescribed at 15MEQ 2tabs twice daily.
        2 months later Litholink test
        urine pH = 6.104.
        24Cit = 621
        The nephrologist took over. No Litholink test ordered for 2017 but another 24hr urine showed urine pH 7.1 so Pot Cit reduced to 3 15MEQ/day.
        2018 Litholink
        urine pH = 6.729
        Cit24=738 so Pot Citrate reduced to 2 15MEQ /day.
        2019 Litholink
        urine pH =6.782
        Cit24 =724 so Pot Citrate reduced to 1 15MEQ/day.
        1 month later urinalysis showed urine pH at <= 5.0 so this dosage insufficient. If the Nephrologist noticed she did not comment or increase dosage and I completely missed this. So unfortunately my husband has been at this urine pH for 6 months before I noticed a few weeks ago and panicked. I understand correct dosage (TBD) should raise urinary pH to above 6. But is it clinically significant that Potassium Citrate dosage has required steady reduction like this?
        Many thanks
        Colleen

        Reply
        • Fredric L Coe

          Hi Colleen, You saw what one does not want to do: If the pH is above 6 is there a reason to make all these changes? Dr Pearle will solve the problem for him, and after that the uric acid will be gone. She will figure out whatever else is wrong, too, as she is a wonderful expert. Send her my warmest regards and let her fix things. Regards to you as well, Fred

          Reply
  4. Natalie Luna

    Dr. Coe,
    I am a 45-year-old woman. I had my first bout of kidney stones about two weeks ago. I had been feeling “off” for several months and all kinds of tests were run because I kept having a trace of blood in my urine and a low-grade fever. including a CT a week before my stone attack and nothing was there–“demonstrated normal kidneys without HDN”. And even at the ER, they didn’t find it but saw that “mild right HDN and stranding around the kidney with dilation to the bladder. No stone or obstructing lesion was noted.”

    I went to the urologist after and did a urine test. My pH is 6.5 and still a trace of blood. Still having some pain on right side and she now wants to do a ” Lasix renogram. If normal, she will FU for cystoscopy in the office. If not, she will require an RGP and cystoscopy in the OR.”

    I am so beside myself that this happened. My sister had Bartters Syndrome and has it it over 20 years. She lives he r life but this one episode has gotten the best of me, especially now that I know I will need more tests.

    My questions are why now? Why at 45? And will I have to do this diet to make sure it doesn’t happen again? I’m guessing yes but it had totally disrupted my life. My anxiety is off the charts and I can barely think, work or eat. I am looking for some guidance.

    Thank you,
    -Natalie

    Reply
    • Fredric L Coe

      Hi Natalie, Your physician is acting as well as anyone would want. Perhaps you are passing some tiny stones, and they are not visible. If there is no sign of any stone a diagnostic cystoscopy is a good idea because of the blood. Though all a big bother, risk is very low, and whatever is found treatment excellent. As for Bartters, there are cases of late onset crystals or stones, but that can wait until your urologist is finished. I would not so much worry as be aggravated at all the bother and time wasting. You have mostly all good alternatives. Regards, Fred Coe

      Reply
  5. Kurt Conrad

    This is an extraordinary website. I am sure it has helps thousands of people.

    I am a 70-year-old male with a history of calcium oxalate stones since age 55. I have finally made a major change in my diet over the past 3-4 months. I am following the guidelines put out by you and Jill Harris, especially in regard to drinking much more liquid and drastically lowering my sodium intake. My question relates to liquid intake. I am putting out about 4,300 mls. of urine every 24-hours because I am making it a point to drinking a lot of water, even when I am not
    thirsty. I am extremely healthy for my age with no ailments whatsoever. I am 5’11” tall and weigh 175 lbs. Is an output
    of 4,300 mls. of urine too much for a man of my age, size and health? Would such a high output, eventually, cause my
    kidney’s or heart to have to work too hard. Thank you.

    Reply
    • Fredric L Coe

      Hi Kurt, No, a high water intake is perfectly safe unless you are taking some medication that affects kidney water excretion. Typical agents are anti anxiety meds. Likewise, diuretics impair water excretion and you need to be careful to avoid falling blood sodium. But absent these issues and rare diseases, water at this level is fine. Be sure your physician knows, has checked off the boxes about meds, and checks a blood once in a while for sodium. During part of our evolution we lived in the lakes and rivers of the world and adapted our kidneys to remove water without sodium with miraculous efficiency. Regards, Fred Coe

      Reply
  6. Jolie Dodd

    Dr. Coe,
    I am so thankful for your service to all of us who suffer kidney stones, Thank you! I am a 62 year old female. I had my 1st stone in 2016 which sent me to the ER in horrible pain. After PCNL surgery my stone analysis was: 60% CA OX dihydrate as a 1st constituent and 40% CA PHOS apatite. I had currently been on a ketogenic diet and then switched to a vegan diet which I now know were both detrimental to my health! My Urologist doesn’t recommend any dietary plan and has not ordered a metabolic blood panel or a 24 hour urine collection either. Should I make an appointment with a Nephrologist? I am afraid to take any CA supplements & am trying to eat dairy rich CA such as Keifer & whole milk yogurt; is whole milk better or low-fat? After PCNL, a fragment of stone was left behind I was told it was small but the lab came back as a 7.5 mm! I asked if he could remove it using uteroscopy and he said no because it was in the Inferior Pole calyx (Right side) and he couldn’t get the basket in that area. He advised ESWL 6 weeks after PCNL but I asked for more time for my kidney to heal completely so he scheduled my x-ray in February 2020. I have concerns about the apatite in my stone. Isn’t this an infectious stone? If so, isn’t it risky to break it up, causing more infectious particles to invade my kidney and create more stones? I am drinking fresh organic lemon juice in distilled water 1/2 C twice daily along with a natural B-Complex and 2-3t. daily (spread out) of Calm brand powdered Ionic Magnesium Citrate. I quit taking all other supplements. Please advise me on your advice to move forward; I am very confused as to what to eat at all…very stressful! I am eating very few oxalates! My current urine Ph is 6.5-7.5 using Ph urine strips and my Parathyroid was in “normal” range. God Bless You! Jolie

    Reply
    • Fredric L Coe

      Hi Jolie, You have significant calcium phosphate in your stone and that is due to the high urine pH, not infection. I am sorry that so large a fragment was left behind. I am not a surgeon and second guessing a surgeon has no good in it. But you might want a second opinion before getting a SWL treatment. Lower pole stones do not clear so well. As for prevention, serum and 24 hour urine studies are essential. Here is a good article on the subject. Home remedies are futile, you need to know what is wrong and aim treatment there. Since the calcium oxalate in the stone was the dihydrate, I assume your problem will be high urine calcium from genetic hypercalciuria. A nephrologist is important as your surgeon is not willing to provide for you. Regards, Fred Coe

      Reply
  7. Cinderpaw

    This instructive data and analysis that you provide can prevent the horrible pain of kidney stones. May you both live forever.

    Reply
  8. Barb

    Thanks for writing this up! As a 60 y/o new stone former, I have asked Jill repeatedly “why now?” The more I learn, the less anxious I am and continue to do all the things I can to control future stone forming.

    Reply
  9. Titi Akinremi

    Thanks for the eye opener.
    Questions please :

    Which is more culpable for stones, alkaline or acid urine? How can I modify my pH?

    Reply
    • Fredric L Coe

      Hi Titi, Both can be a problem. Too low a pH – below 5.3 can foster uric acid stones. Too high a pH – above 6.5 or so calcium phosphate stones. It is kind of like the Three Bears. The safe approach if you have stones is to get 24 hour urine testing and find out what causes the stones. Here is my best on that. Regards, Fred Coe

      Reply

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