24-hour Supersaturation Profile
Metabolic evaluation for kidney stone prevention
Dr Nimeh might order a 24 hour urine supersaturation profile. Why?
Prevention of kidney stones is seriously important if you want to avoid the pain of childbirth at the most inopportune moments (e.g. in a music concert or when you're on your Hawaii vacation).
The way to do it is not by analyzing the stone that you've already passed (sorry), but rather by doing the ever-so-annoying 24h-hour urine supersaturation evaluation. You have to collect all the urine you make for 24 hours and safely keep it in a container to be analyzed. then 1 to 2 weeks later you get a full report. How can this help you? well read below and discover the wonders of the ever-so-precious 24 hours urine supersaturation report!
Units of 24 hour Urine Measurements
Because excretions of stone risk factors are in amount per 24 hours, we need the time of the collection. You provide the beginning and end times for the collection, in minutes and hours, and the laboratory corrects all excretion values to amounts in 24 hours.
For example, you start a urine collection at 7 am and complete it at 5 am the next morning. The measured total time is 22 hours. If the volume is 1.5 liters, the volume ‘corrected’ to 24 hours is 1.5 liters x 24 /22 (1.09) or 1.636 liters/24 hours.
It is obvious that the less ‘correcting’ the better, because the ‘correction’ assumes that every hour is the same as every other hour, which is not likely. So you want to collect as close to 24 hours as possible. If your time is below 22 or above 26 hours throw it away – no cost – and do another.
I am sure this is an unnecessary comment but sometimes people forget that a urine collection begins by emptying the bladder, writing down the time, and discarding the urine. Here and there people add it, making the real collection from whenever the bladder had last been emptied.
Volume per 24 Hours
Urine volume is measured in liters (L) or milliliters (ml). A milliliter is 1/1,000 of a liter, so there are 1,000 ml in a liter. One liter is 1.06 quarts. The laboratory measures the total volume of urine if you send or bring it. Often you will read the volume yourself, off of a collection container.
Because excretion rates like calcium, oxalate, citrate, and uric acid are calculated by multiplying their concentrations by the 24 hour volume, mistakes in timing, collection, or measurement of volume will make the results less valid. You provide the collection times, assure all the urine has been collected, and even may measure the volume, so quality is under your control.
Urine creatinine, calcium, oxalate, phosphate, and citrate excretions, are in milligrams (mg) or grams (gm) per 24 hours. A mg is 1/1,000 of a gram. An ounce contains 28.3 gm.
Urine sodium is measured in millimoles (mmol) or milliequivalents (mEq)/24 hours. Atoms, like sodium, each have a weight made up mainly of their constituent protons and neutrons. One mmol of sodium is 23 mg.
Some atoms like calcium have two charged sites which can bind to other molecules or atoms. They are often measured in milliequivalents (mEq) which is the weight times the number of sites. Sodium has only one, so mmol and mEq are the same.
Molecules like creatinine and oxalate have weights made up of their constituent atoms.
Acidity or alkalinity are measured in pH – no units. It is a logarithm to the base 10 so a change from 6 to 5 means a 10 fold increase in acidity, from 6 to 7 a ten fold increase in alkalinity.
Supersaturations are calculated from urine concentrations. The one we use here is the ratio of the concentration dissolved in urine of each of the three important stone forming salts, calcium oxalate, calcium phosphate, and uric acid divided by their individual solubilities at body temperature. Values below 1 mean crystals will dissolve. Values at one mean crystals will neither grow nor shrink nor form. Values above 1 mean crystals can form and grow. Being a ratio it has no units.
Is The 24 Hour Urine Valid?
Like all 24 hour excretion rates, that for creatinine is calculated from the concentration, measured volume, and collection time.
Because muscle cells make almost all the creatinine lost in urine any two urines you collect will have about the same amount of creatinine in them. A more than 20% variation between two urines suggests an error in one collection. If there are many collections, most creatinine excretions will line up pretty well, and an outlier – too high or low by more than 20% of the average for all the collections will stand out.
When a urine stands out as different from prior collections, I say it is best to repeat it. If there are two, use the one that seems more correct.
‘More correct’ is judged by expected amounts of urine creatinine. For men, one expects about 18 – 24 mg/kg body weight; for women, 16 – 22. A urine far out of those ranges is suspect. In people who have a high body fat percentage the ratio can be as low as 12 mg/kg/day, and people who have little body fat and a high muscle mass can be as high as 30 mg/kg/day.
Conditions of Collection
Did you eat and drink as usual, or show off? Had you ‘improved things’ since a recent stone so your collections reflect new habits and not those that led to the stones? Every collection is a one day frame out of a movie that is running 365 frames a year, so if these few days do not reliably represent your average life, their results will inevitably mislead you and your physicians and falsify what you came to do.
Reading the Results
To decrease your stone risk you need to be drinking enough water to produce 2.5 – 3 liters liters/24 hours according to studies.
Stone risk increases with urine calcium excretion above 200 mg/day in men and women.
If you have above 200 mg/24 hours you have ‘hypercalciuria’, a high enough calcium to pose risk of stones – and also bone disease. There are many causes of hypercalciuria. The commonest is simply a genetic tendency, called idiopathic hypercalciuria. ‘Idiopathic’ means your physician has ruled out any of the other causes of hypercalciuria.
You lower urine calcium in idiopathic hypercalciuria with reduced diet sodium, avoidance of sugar loads, and medications if needed. You compare treated to untreated excretion to see how well the treatment worked.
Urine sodium is essentially the diet sodium intake. Because urine losses can lag intake when intake varies sharply, urine sodium is a good estimate of the average over 3 – 4 days. If you tried to lower your diet sodium to 100 mmol/24 hours, 2,300 mg intake, and you find 200 mmol/24 hours, you can be sure that your average intake is on average twice what you desired.
Suppose your urine calcium is 250 mg/24 hours, urine sodium 200 mmol/24 hours – twice the upper limit of diet sodium in the US and above the optimal value of 65 mmol (about 1,500 mg/24 hours). You would want to lower your diet sodium. Suppose your urine sodium was already 65 mmol/24 hours and urine calcium was 250 mg/24 hours; you would want to take other steps like thiazide diuretics (thiazides are a type of diureteic which helps your kidney hold on to calcium and avoid excreting it in the urine) or potassium citrate (citrate helps prevent the molecules from coming together and making stones).
What if your urine calcium is 450 mg and your urine sodium is 200 mmol? Sounds like a bigger problem, but it is not. When urine calcium is higher the slope dependency of urine calcium on urine sodium is steeper, so the same reduction of sodium could bring urine calcium quite a way down.
If you lowered diet sodium and there is no change, do not assume the test is wrong. Check the creatinine values – do they match? If so, you have not lowered your average sodium intake. Sodium is an atom and you are not a cyclotron; you cannot make sodium or destroy it.
Stone risk increases with increasing urine oxalate and if the risk ratio is not as high as for calcium risk appears at very low levels of excretion – above 25 mg/day. In general, high urine oxalate comes from high oxalate diets, low calcium diets, or the combination of high oxalate and low calcium together. Therefore treatment is dietary. Excellent food lists are in this site – linked from the oxalate diet article. Rarely, urine oxalate is raised from a hereditary overproduction state – primary hyperoxaluria. Likewise, bowel diseases can raise urine oxalate. These are complex conditions and diet alone is rarely enough.
If urine oxalate is high and you have corrected both your diet oxalate intake and added significant diet calcium, you may have some form of genetic or acquired oxalate overproduction or an otherwise inapparent intestinal absorption problem.
Citrate is a powerful force against calcium stones. It binds calcium in a soluble complex. It interferes with calcium crystal formation and growth. Low urine citrate is a risk factor for new stone onset – bottom left panel of the graph. Above 400 mg daily there is no extra risk of stones in men or women, so ‘hypocitraturia’ means a urine citrate below 400 mg daily.
If you begin taking, as an example, four 10 mEq potassium citrate pills a day – 40 mEq, that extra 40 mEq of potassium should appear in the urine. If it is not there, the pills may not be delivering the medication into the blood from the bowel. The urine pH should rise because citrate imposes an alkali load. If it does not and the urine potassium does rise, you may need more of the medication.
Urine ammonia – I will cover this in the second half of this two part article – is a major way the body removes acid, so when you take citrate ammonia excretion should fall. If it does not fall, and urine potassium rises perhaps your pills are potassium chloride – the pharmacist switched from what was prescribed.
Strangely, the urine citrate itself does not rise in everyone even when potassium and pH rise and ammonia falls.
A low value – below 5.5 poses a risk of uric acid stones. A high value, above 6.2 raises calcium phosphate supersaturationand risk of calcium phosphate stones. Potassium citrate can raise urine pH; there are no medications to lower urine pH except methionine and ammonium chloride and these are not usable for stone prevention because they will increase urine calcium and pose a risk of bone mineral loss.
Relate Them To Your Stone Crystals
There will be three supersaturations: Calcium oxalate, calcium phosphate, and uric acid. Inspect the ones related to your stone crystals. For calcium oxalate both calcium oxalate and calcium phosphate supersaturations matter. If calcium phosphate, that one matters most. If pure uric acid, it is uric acid supersaturation.
One should not compare values in a stone former to values in normal people, who often have urine supersaturations as high or higher than those of stone formers. Active stone formation means supersaturation is too high for you whatever the value may be and needs to be lower. You reduce your supersaturations by increasing urine volume and reducing excretions of calcium and oxalate, or raising excretion of citrate without undue increase of urine pH. That is why we make these measurements.
Compare Then to Now
Compare you now to you before your most recent fluid and diet intakes or medications: If they have fallen, things are going well; if they have risen things are not going well. If stones are still forming, supersaturations need to be lower. If there have been no more stones and supersaturations are stable, stand pat. If supersaturations are below 1 and stones are still forming, the urine samples do not properly represent your real life.
A Good Schedule
When? I like two 24 hour urines before treatment – it gives a sense of averages. After treatment has begun – diet changes, fluid goals, lifestyle, it is important to get another. The timing is up to patients: You know when something has changed, or ought to have changed, and need to be sure it has indeed changed in the right direction. It goes on like that until treatment is reaching its goals – lowering supersaturation by at least half – after which once a year is a good idea.