HOW TO READ YOUR KIDNEY STONE LAB REPORT – Uric Acid Stones

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The pretty picture shows uric acid crystals in urine magnified 400x under polarized light to bring out their shapes with special clarity.

Here is what to look for and what to do if your stones have uric acid in them or are entirely uric acid.

A caution: Occasional stones are not uric acid but a salt of uric acid: Sodium hydrogen urate or ammonium hydrogen urate. This article is not for them, They occur in unusual situations, not as yet covered here or anywhere else on this site.

Urine pH

220px-Harnsäure_Ketoform.svgUric acid is a large carbon based molecule. Water ‘dissolves’ molecules because of charge attraction. But there is not a lot of charge on this kind of molecule. In fact there are only two sites, both negative and both where nitrogens (N) are. One of them is set up so that it is always blocked by a positively charged proton (H), the other, the nitrogen (N) at the lower right of the molecule can be blocked or not depending on the pH of the urine.

At a pH of 5.35 about 1/2 of the uric acid molecules will be blocked and one half will have an open (negatively charged) nitrogen at the lower right. It is this one site to which water molecules can bind to hold the molecule in solution so it does not crystallize and produce stones and gravel.

Each kink where two lines join in this drawing is an atom. Carbons are just kinks, nitrogens hydrogens and oxygens are labelled. So, count them: Nine in the two rings, 3 oxygens (O), four nitrogens (N) and 1 to 2 protons (H) making 16 – 17 atoms with only one charge site.

two_H20_moleculesWater molecules have three charges for three atoms. One end of the big red oxygen atom has the two protons (the two H of H2O) bound to it which are positively charged. The other side of the oxygen atom has a negative charge (- sign along the bottom of the big ball). The two water molecules shown here pull each other together because the proton (positive) atoms attract the oxygen atoms (opposites attract), and that is why water is continuous – you can swim through it, pour it, drink it – and cannot pulled it apart.

Imagine this in three D. Water is innumerable of these molecules holding each other positive to negative sides even though when we drink it we would never know how it was put together. Because there is one charge per atom, there is a lot of force holding these atoms together.

Now, imagine uric acid swimming among these water molecules. The small positive balls, protons, will bind to the negative nitrogen (N) on the big carbon ring, and only that will keep uric acid ‘in solution’, which means the uric acid will be held in among the water molecules as if it were one – though it is too large to really fit in smoothly and has very little charge (1 site for 16 – 17 atoms) compared to water which has 3 charges for three atoms.

The form of uric acid with one charge is called urate, denoting it has a charge and can form a salt pair with another atom or molecule, like calcium does with oxalate or phosphate, or sodium does with chloride. The usual salts are sodium and ammonium urate. One can dissolve hundreds of milligrams of uric acid as urate in a liter of urine.

As you begin blocking the one charged site with protons (1/2 blocked at pH 5.35) less and less can be in solution. When both sites are ‘entirely’ blocked there is only a tiny residual charge and no more than 90 mg of this ‘uric acid’ – ‘acid’ because having both its protons – can be dissolved. The little bit dissolved is because of residual charge shining through or around the blocking protons (I realize my imagery is not exact here, those of you in the business will forgive me).

I have taken some time and space over this detailed matter because it is more or less all anyone needs to know about uric acid stones.

Urine Supersaturation vs. Urine pH

Urine UA SS vs Urine pH

If you do not already know about supersaturation, stop here and read the Five Steps of Stone Prevention. Values above one mean uric acid crystals – and therefore stones – can form and grow. Below one, uric acid crystals cannot form, and those already present can indeed dissolve – albeit slowly.

Each point on this graph comes from a single 24 hour urine collected mostly by me in my stone clinic at University of Chicago. The horizontal dashed line at 1 is the supersaturation demarcator I just referred to – above it is supersaturation, below it is undersaturation.

The vertical dashed line at pH 6 is the perfect place. Below it, supersaturation becomes increasingly common as you can tell by the fraction of tiny points above 1. Above 6 only a tiny fraction of points are above one – in the lower left corner of the upper right quadrant of the graph.

Urine volume, and the total amount of uric acid excreted have an effect – that is why the graph is a thick band and not a thin line, but pH is so overwhelming it takes all of the real clinical focus.

Read Your Report

Uric Acid Supersaturation is Above 1

Is it above 1? Lower it. The ways are simple. Raise urine volume above 2.5 liters daily and raise urine pH just above 6. Recheck in a few weeks, and adjust if necessary. When supersaturation is below 1 and pH about 6 you are done, but be sure and check again at 6 months – habits can be difficult to change long term.

Calcium phosphate stones are fostered by too high a pH, so just above 6 is enough!

Sometimes just very low urine volumes can create a supersaturation for uric acid above 1 even at a urine pH of 6. Though uncommon there are a few points with such supersaturations in the right upper quadrant of the graph above, as I have noted. Simply raise urine volume, recheck, and if supersaturation is now very low and pH still about 6 perhaps that is all you need to do.

Uric Acid Supersaturation is Below 1

Is uric acid supersaturation below 1?

You have a problem.

The urine you are producing could not have supported uric acid stone formation, yet you did indeed make such stones.

This means something has changed from when you made the uric acid crystals and when you collected the urine. One possibility is that you know what it was, the change is permanent, and you have cured yourself.

The other possibility is that you do not know what it was that changed, and you therefore do not know when those risks for uric acid formation will return. Perhaps your physician can prompt you but frankly it is mostly up to you to think about what might have happened. Were you dehydrated a lot of the time? Had your diet been odd? For example popular all protein diets for weight loss might lower urine pH a lot.

How to Increase Urine pH

Assuming you are the usual uric acid stone former you will increase urine volume and pH. The former is higher fluids, and the latter is some form of alkali, usually potassium citrate.

Potassium Citrate

The pills are 10 mEq (units are in the prior article on reading your reports) each. No one can know exactly how much to give at first but a common starting place is 2 twice a day or 40 mEq. The day contains 1,440 minutes and we want the urine pH to be as even as possible for all of them, and not very acidic (below 5.35) for any of them. That is one reason for using two doses a day. An even more ideal dosing would be 3 daily but people tend to miss the middle dose.

Citrate is not an alkali and cannot itself make the urine alkaline. It works because it is metabolized in the liver and kidney in such a way as to create bicarbonate – the buffer of the blood. Sodium or potassium bicarbonate themselves could make urine more alkaline, obviously, but they have a drawback. The sodium salt imposes a sodium load which could raise blood pressure. Either salt will be absorbed rapidly and create a relatively short spike in urine pH compared to citrate which is absorbed and then metabolized – a slower process that gives a more even urine pH result.

Because of regrettable increases in pricing by the few manufacturers of potassium citrate and an unwillingness of insurance companies to pay numerous workarounds have been proposed on this site. But all of these involve use of an alkali so lab changes are much the same.

Other Alkali Sources

One commercial beverage, Crystal Light contains in one liter the same alkali amount as two 10 mEq potassium citrate pills, and it is inexpensive. A common approach is to use it to replace a two tablet dose as desired, and the extra fluid can count toward the day’s needs.

Sodium bicarbonate tablets – 2 10 grain tablets – can be purchased OTC and will more or less make up the alkali of one 10 mEq potassium citrate tablet. The sodium load of 40 – 50 mEq daily is not ideal, and absorption and urine loss are rapid so the treatment is more likely to worsen hypertension and more fleeting.

Lemons and other fruits. There is no doubt that citrus fruits contain citric acid, but the amount of citrate will depend on the amount of the acid that is in the citrate – not the acid form. One half cup of Real Lemon provides just 6 mEq of citrate and has to be dissolved in a lot of water and sweetened. The link shows all of the beverages and juices for which we have measurements. The extensive comments are very valuable and have in them a lot of practical ideas.

Do Another 24 Hour Urine with a Blood 

As I mentioned in passing before, one expects certain changes in urine with potassium citrate, so lets look for them.

Urine Potassium

If you take it you should find it in the urine. So if the baseline urine potassium was 40 mEq/24 hours, and you added 40 mEq/24 hours you should expect 80 mEq/24 hours. In general this will be true. But unlike diet sodium that is almost totally absorbed and excreted in the urine, potassium may not be completely absorbed, and some may enter the vast cell potassium stores or even be excreted by the intestine itself.

A good reading of the lab sheet is, nevertheless like this. Urine potassium should rise more or less in proportion to the potassium citrate dose – if there is no rise, the material is not being absorbed.

Urine pH

You should expect a rise in pH and your goal is about a pH of 6. There is no benefit to much higher, and a real risk that too high a pH (above 6.3) will increase supersaturation with respect to calcium phosphate and possible new stones of that mineral.

If the pH has not risen enough, check the urine potassium. Did it rise more or less in line with the dose? If not, perhaps the drug absorption is too low or you missed a dose. If it did rise, then you need more alkali. So, in either event, increase the dose of alkali. A good formula is to go from 2 twice daily to 2 three times daily – longer span of treatment, but do not skip the middle dose!

If the pH has not risen at all, become suspicious.

If the urine potassium did not rise as expected, suspect the tablets are not delivering the drug from their binding envelope. If the urine potassium did go up as expected, the pharmacy probably has substituted potassium chloride for potassium citrate. That is legal as people usually are after the potassium.

Urine pH test strips are a useful day to day checkup especially if stones keep forming. Dips are smoothed out in 24 hour urines. Walmart, Amazon, and CVS all have inexpensive urine pH strips. Shop for price and colors that work for you.

But even with strips as an ad hoc monitor do 24 hour follow up tests because they are your average, and the average is the overall effects on crystals in a day. The two approaches are complementary.

Urine Ammonia and Sulfate

Because kidneys remove acid from the body via ammonia excretion – about 2/3 of the total daily, giving an alkali will lower urine ammonia excretion. But there is a special problem: How do we know if the acid load itself has changed?

The answer is the urine sulfate, and here we are entering into real professional reading of laboratory tests. Sulfate is the final oxidation product of sulfur molecules on cystine and methionine, two amino acids; as it is oxidized this sulfer is converted to sulfuric acid. That is a principal part of the daily acid load. The amounts are perhaps 2 to 4 mEq per kg of body weight but vary with meal choices.

Your 24 hour urine test should have urine sulfate as well as urine ammonia and you use them together to assess the effects of your alkali treatment. Whatever the alkali, citrate, bicarbonate, pills, beverages, juices, ammonia will fall in relation to sulfate.

Lets do an example. Your baseline – before treatment urine sulfate is 50 mEq/24 hours, your ammonia excretion is 40 mEq/24 hours (the ammonia is almost always below the sulfate because the kidney has other ways of removing acid), and the pH is 5. You take 40 mEq of potassium citrate. The next urine shows 60 mEq of sulfate – more protein intake that day, perhaps, and the ammonia is 15 mEq: This is what one expects in a general sense.

You will usually not be able to add up the exact changes in ammonia, dose of citrate, and changes in sulfate as in an accounting lesson: Too many ways the system can respond. But the general sense is that ammonia must fall in relation to sulfate, and in a fairly reasonable approximation to the dose of citrate.

Urine Citrate

Surprisingly, urine citrate might not rise much even though ammonia is suppressed, and urine potassium and pH rise. Citrate handling is very complex, and in this area of disease all we really care about is the pH so that uric acid will not crystallize.

Some people, especially those with diabetes or so called ‘pre-diabetic’ people with insulin resistance may have very high citrate excretions, as high as 1,500 to 2,000 mg/24 hours. When you give potassium citrate, sometimes urine citrate rises so much that a significant portion of the dose is simply lost in the urine and not metabolized to bicarbonate. If so, simply use more.

Urine Uric Acid

I have not even mentioned how much uric acid you excrete daily because it has virtually no influence on whether uric acid stones will form. But it can change in what will appear an odd manner.

Not rarely, when urine pH is low, uric acid is crystallizing out of the urine in the 24 hour urine collection container, or even in you, so the amount in 24 hours will be normal or low. When the pH is increased, the amount will ‘increase’ because no more is crystallizing, and people – even physicians – can wonder why. Why is because none is being lost through crystallization.

Drugs and diets that aim to lower uric acid production and excretion have no role in prevention of uric acid stones. Fluids and alkali are all that matter.

30 Responses to “HOW TO READ YOUR KIDNEY STONE LAB REPORT – Uric Acid Stones”

  1. Jason

    Hi Dr. Coe,
    With regard to your Uric Acid SS vs pH graph, I think I can understand that if I increase my urine pH, my SS can be lowered below 1. It doesn’t work in the reverse, correct? i.e. if I lower my SS (by drinking lots of water), does my urine pH increase correspondingly?
    Also how much does the pH of the water I drink have an impact on my urine pH? Can high pH water be used to dissolve uric acid stones instead of K citrate?

    Best Regards
    Jason

    Reply
    • Fredric Coe, MD

      Hi Jason, I want to be sure I am not doing you a disservice. I am answering detached questions for you but perhaps they might mislead your care. Do you in fact have uric acid stones? Do you have a physician to care for you? Taking on diet or other factors to alter urine pH is not always good. Higher urine volumes are, however. Perhaps you might clarify matters a bit more for me so I am sure I am doing no harm. Regards, Fred Coe

      Reply
      • Jason

        Hi Dr Coe,
        Sorry I shouldn’t have written in the first person. My uncle has had uric acid stones, I was trying to explain to him the science behind it. Maybe you can explain just the graph, since I don’t know all the details of his case.

        In the Uric acid SS vs pH graph, if one decrease the SS below 1 (by drinking lots of water), does that automatically increase the pH level of the urine? or only the converse is true (i.e. by increasing pH level, the SS will drop below 1).

        Thanks

        Jason

        Reply
        • Fredric Coe, MD

          Hi Jason, Only change of pH matters. The graph shows SS vs. pH; there is no water or urine volume on the graph. Water will not do it. Regards, Fred Coe

          Reply
  2. Jason

    Hi Dr. Coe,

    Very interesting article. When trying to identify uric acid stones (vs non uric acid) in the kidney are you familiar with Dual Energy CT scans? Is this technique widely available and is it accurate in predicting uric acid stones? Please see link below for reference.

    http://www.scbtmr.org/Portals/9/Meetings/2012/Final%20stone%20Dx%20and%20Mt%20SCBT%202010.pdf

    Thanks
    Jason

    Reply
    • Fredric Coe, MD

      Hi Jason, The link you sent dead ends so I cannot read the paper. I am not aware of dual energy CT for this purpose but for uric acid routine CT is not too bad because the density of uric acid stones is lower than for the others. Regards, Fred Coe

      Reply
      • Jason

        Hi Dr. Coe.

        Sorry the link didn’t work. Here is another link.

        Since you said routine CT is not too bad, below what HU density would you consider it to be uric acid stones?

        http://www.massgeneral.org/imaging/news/radrounds/july_2008/

        Regards

        Jason

        Reply
        • Fredric Coe, MD

          Hi Jason, Thanks. I gather the dual scanner is good for uric acid but not so good for cystine, struvite and mixed stones. As such, perhaps, it is good for stones with low HU that might reflect poor centering or small size. HU below 500 raise suspicion of uric acid, especially when stones are large. I did not see the additional radiation dose or cost estimates but one would have to weight the modest improvement against both. Very interesting. Regards, Fred

          Reply
          • Jason

            Thanks Dr. Coe,

            What is the size demarcation between a large stone and small stone?

            Regards
            Jason

            Reply
            • Fredric Coe, MD

              Hi Jason, It depends. If we are speaking about passing, probability begins to go down at 5 mm and becomes low above 7 mm. If we are talking about large enough to need percutaneous nephrolithotomy and contra-indicate SWL it is 20 mm. Regards, Fred Coe

              Reply
              • Jason

                Hi Dr. Coe,

                I think you misunderstood. I meant it in the context of your answer to the previous question. You said “HU below 500 raise suspicion of uric acid, especially when stones are large”. What size of stone would you consider large as opposed to small, where HU is not reliable?

                Regards
                Jason

              • Fredric Coe, MD

                Hi Jason, Stones of less than 2 – 3 mm are hard to image, so large enough for HU is perhaps 4 mm, depending on the quality of the CT. Regards, Fred Coe

  3. Anna

    Hi Dr Coe,
    An ultrasound shows 13mm stone. This current stone has formed since lithotripsy (x 2) to remove a 3cm calcium oxalate stone a year ago. It was assumed to be the same sort until it was not seen in a recent X-ray. I have been maintaining an increased fluid intake and about 3/4cup of fresh lemon juice daily for Several months before current ston was discovered as a preventive measure. Recent fasting blood and 24 hour urine show volumes just over 4l they do not show ph or supersaturations though everything else is within normal range –
    9/1/17
    Creatinine 6.9 mol + citrate 3.8 mmol + oxalate 0.32 mmol)
    19/1/17
    creatinine 11mmol + calciul 5.3
    6/2/17
    creatinine 10+ Urate 2 mmol
    Could it still be a uric acid stone?
    Thanks for reading,
    Anna

    Reply
    • Fredric Coe, MD

      Hi Anna, Perhaps the 4 liters of volume is not always present – perhaps during the day it varies too much. Your calcium is high – 5.3 mmol (>200 mg/day) poses risk. Without a urine pH one can say nothing about uric acid, but your stone was calcium oxalate and the new one is likely to be the same. Here is the problem, the 24 hour studies are fragmented and incomplete – no supersaturations, no pH, no sodium; can your physicians obtain better for you? If not the only approach is to assume calcium oxalate and pursue prevention via diet and if needed medications. I presume you have no known diseases causing the stones. Regards, Fred Coe

      Reply
      • Anna

        Thanks for responding – I will follow up with my Gp regarding supersaturations, sodium & ph – I was hopeful it would not be calcium oxalate as it didn’t show on a plain X-ray – but I do understand that different types of stones can coexist and I imagine that can leave room for doubt? from what you’ve shared here it seems I need to focus mainly on calcium oxalate prevention and not worry about ph unless it is flagged as an issue in any further testing. I’m very grateful for your input Dr Coe.
        Kind regards,
        Anna

        Reply
  4. dshino

    Would not allopurinol help lower uric acid production and be helpful in those whose liver produces too much?

    Reply
  5. Al R.

    Hi Dr. Coe,
    Could you please try to help me understand the implications of “the ammonia is almost always below the sulfate because the kidney has other ways of removing acid”.
    Say NH4 24 was initially around 25 and Sul 24 around 50. Then after starting Chlorthalidone 25 mg, (no potassium citrate yet and fairly constant diet), both NH4 and Sul24 were around 50. And this pattern has persisted for a year even with various doses of potassium citrate from 5 to 40 mEq. NH4 went even higher at times with no infection or other known cause.
    Any idea why this might happen and whether it provides any clues as to how the body is or isn’t handling acid excretion normally?
    Appreciate your time. Best regards,
    Al

    Reply
    • Fredric Coe, MD

      Hi Al, ammonia will normally be below sulfate for the reason you mention. Chlorthalidone invariably causes some potassium loss from cells – serum normal – and the kidney responds with increased ammonia. Take a look here. Regards, Fred

      Reply
      • Al R.

        Hi Dr. Coe,
        Thanks very much for your reply. That is a familiar article. A challenging, but rewarding read!
        Your hypothesis makes sense, so let’s test it with the most trusted data from the last year:

        Chlorthalidone/Potassium Citrate -> blood potassium, NH4 24, Sul 24
        0mg/0mEq -> K=4.0, NH4=29, Sul=48 (baseline)
        25mg/0mEq -> K=3.8, NH4=59, Sul=59
        50mg/40mEq -> K=3.8, NH4=52, Sul=53
        25mg/5mEq -> K=3.7, NH4=61, Sul=49
        Wow, does it make sense that the slope of the curve could really be that steep? I didn’t realize a change of 0.2 in potassium could be so significant.
        Take care,
        Al

        Reply
        • Fredric Coe, MD

          Hi Al, Most potassium is in cells, so when serum falls a very little bit it usually means cells have lost appreciable potassium. The cells know that and kidney cells respond with – among other things – a rise in ammonia production. pH inside the cells fall. Nice observations. Regards, Fred

          Reply
  6. John Davis

    Dr. Coe,
    You mention above:
    “Below one, uric acid crystals cannot form, and those already present can indeed dissolve – albeit slowly.”
    Is there any way to understand the rate of dissolution for Uric Acid stones already present? I have several large Uric Acid stones 12 and 18mm in my left kidney as seen on a CT scan. I have started on Urocit-K and increased my pH above 6. I am curious about how long it may take to dissolve stones of this size. Working with my Urologist, I am scheduled for another CT scan in 3-4 mos. Is this enough time to see a noticeable reduction in size provided I can maintain the higher pH? Is there any benefit to even higher pH – above your recommended 6.3 – to dissolve existing stones?
    Thank you in advance.

    Reply
    • Fredric Coe, MD

      Hi John, The rate of volume loss is dependent on the size of the stones as loss occurs off of the surface out of the volume, and the surface/volume ratio is ~1/r. Raising the pH much above 6.3 is not wise as calcium phosphate crystals can be promoted and at pH 6.3 you are 1 pH unit above the uric acid pHa and SS UA will below 1. The stones are almost certainly not singular but made up of smaller stones glued together, so the 18 mm one will probably begin to break up into smaller stones. Message: wait, leave the pH where it is. Regards, Fred Coe

      Reply
      • John Davis

        Thank you Dr. Coe! I really appreciate your response. This site is extremely helpful for patients dealing with stones. Your no-nonsense practical approach to dealing with this wonderful. I am glad I happened upon your site this morning. Have a great weekend!

        Reply
  7. Jesse Goldman, MD

    Hello Dr. Coe,
    I certainly understand that drinking more and diluting ones urine decreases supersaturation. My question: When acutely increasing fluid intake over a few days, is there a net change in total daily urinary uric acid excretion until new steady state achieved? Perhaps due to mild hypervolemia decreasing renal urate rebsorbtion?. If so, can you point me toward a reference in the literature? thank you in advance. Jesse

    Reply
    • Fredric Coe, MD

      Hi Jesse, Thanks for the comment. If the drinking is water, there will be no effects on uric acid excretion but if the beverages impose a sodium load there may be because proximal reabsorption will fall and URAT – the transporter – can be affected. Water alone will not volume expand in an otherwise normal person as fall in VP will immediately lower CD water reabsorption. Even so the effects of sodium will be small. But, if SS falls and there has been prior crystallization – very common – then the urine uric acid excretion can rise dramatically, essentially to its true level. This is a very deceptive picture because the low volume uric acid SS will be around 1 when crystallization is occurring and may even rise as volume goes up! Regards, Fred

      Reply
  8. Robert Howard

    The 5/4/2015 test results were from Highland Park Hospital. Since then, I have had other tests (including a CAT scan). I am under the care of Dr. Zissman and the U of Chicago Hospital. I did a 24 hour urine collection (or 2 or 3 – I forget) and did a blood draw in the Summer/Fall 2015 and I don’t know how to find the test results. I was hoping to see something showing my results compared to the normal range. I suppose I could ask Dr. Zissman, but I assume that she would contact me if there was some issue. So I responded to your articles. Thanks for your help.
    Bob

    Reply
    • Fredric Coe, MD

      Hi Robert, I guess there are two questions here. I presume that Dr Zisman has or will soon talk to you about your results. The other level is for you to get your own results and look at them on your own. For the former, I would call her directly. For the latter, you should have your results and look at them as the article says- it is not normal ranges but stone risk and the article shows that for calcium, volume, oxalate, citrate and the supersaturations. Let me know here if the article does not do it for you because I will want to know – editing online is easy! Regards, Fred

      Reply
  9. Robert Howard

    How do I access my “Kidney Stone Lab Report?”

    I went to the North Shore Connect website . Under “Test Results” the newest item is 5/04/2015

    thanks,

    Bob Howard

    Reply

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