WATER LOWERS SUPERSATURATION
Supersaturation is What Drives Stone Crystal Formation
This point has already been made in other posts. Because we can measure it in standard medical practice, and because it is fundamental in stone formation, we have chosen supersaturation as a basis for estimating fluid needs in stone treatment.
The principle involved is this: The kidneys perform work to make urine supersaturated; the stored energy from that work makes stone crystals form. Drinking extra water relieves kidneys from the necessity of supersaturating urine, which is what we desire for stone prevention.
But, how do we decide how much water?
Supersaturation is Stored Energy
Stir Sugar Into Water. The solution is inert.
Remember the post on sugar and water? You can stir sugar into water all you like, but the water will only dissolve so much. It becomes saturated with the sugar. It cannot take up any more no matter how long you stir. The sugar concentration is said to be at the solubility point.
Filter off that water. It cannot make a single crystal of sugar. Put back some crystals. They cannot shrink or grow. The water cannot release any sugar into them, having exactly what it can hold. It cannot take any sugar from them, for the same reason.
Warm the Water. Add More Sugar. Cool it Again. That Solution Has Energy In it.
Warm the water and keep adding more sugar. More sugar will dissolve because solubility rises with temperature. Let it cool. Solubility will fall, but the ‘extra’ sugar is still there. The solution is ‘supersaturated’. It holds more sugar than it could have dissolved without the heating and cooling.
Evaporate Some Water. That Solution Has Energy In it.
As an alternative, take your original solution, the one at solubility, and let some water evaporate. Warm it with a hairdryer to speed things up. The amount of sugar will remain the same, but there is less water. The solution is supersaturated; it has ‘extra’ sugar in it.
It Takes Work To Store Energy As Supersaturation
You have done work on both solutions. In the first, you put in heat and took it back out. In the second case, you added heat to remove water into vapor.
The extra sugar in both cases is leftover energy. It can make crystals form. If you put this supersaturated solution over some sugar crystals, they will grow. Change in temperature and evaporation are the two main ways to create supersaturations.
Add Water to The Supersaturated Solution That Has Energy In It
Take your supersaturated solution, the one you heated to dissolve more sugar then cooled so it has energy stored in it, and add water. If you use tables of solubility and do the arithmetic, you can increase the volume to exact point needed to dissolve the ‘extra’ sugar.
If you do not want to bother so much, lets just do the experiment in your mind.
Add water. As you add it, you will pass through the point where there is enough to dissolve all the ‘extra’ sugar – the solubility point where we started by simply stirring sugar into the water in the first place. Add even more water. The solution will become ‘undersaturated’. It would dissolve new sugar crystals if you added them in and stirred.
Kidneys Supersaturate Urine By Doing Work
Kidneys Filter Water Out of Blood and Reabsorb all but 2% – 3% of the Water
Kidneys use the work of the heart to filter a large amount of water out of the blood every day: About 140 liters as a crude average, which is 36.98 gallons.
People in general produce about 1 – 2 liters of urine a day, which is 0.26 to 0.52 gallons. So the kidneys concentrate the filtrate by 70 to 140 fold. This process of removing the water from the filtrate back into the blood requires energy and does work on the solution. It is essentially identical to the evaporation experiments we have already spoken about in the preceding paragraph.
Kidneys Filter Salts Out of Blood and Reabsorb Variable Amounts
Some molecules that produce stones, like oxalate, play no useful role in the body and need to be removed. The amount removed depends on how much is produced in the body and absorbed from foods.
Others like calcium and phosphate are conserved by complex biologies as well as by how much is absorbed from foods.
Stone formers tend as a group to conserve calcium less well than normals, so for any amount of water the amount of calcium is higher than in normals.
Supersaturation Reflects the Proportion Between Reabsorption of Water and Salts
Crudely and incompletely put – there is a lot of complexity here! – people make kidney stones in part because of an imbalance between urine losses of calcium, oxalate, and water. Whether this imbalance arises from genetics, habits, vocation, systemic disease, or chance, it can produce or increase supersaturation.
Water is Retained Or Lost To Regulate Blood Salt Concentration
Kidneys pay no heed to supersaturation that we know of. They remove extra water we drink so blood salts are not diluted, and they do this rapidly. If we do not drink, they conserve water so blood salts are not concentrated. So in fact we regulate our own urine volumes and can therefore determine if our urine is supersaturated more or less or perhaps even not at all.
Which Supersaturations Matter to You?
The ones that relate to the crystals in the stones you make.
You know what they are from the stone analyses your physician obtained when you passed the stones or they were removed. The supersaturation in your urine permitted those crystals to form. The purpose of all the extra fluids we have been writing about in this site is to add water to the urine so those supersaturations fall and more crystals will not form.
If you have the common calcium oxalate stones then both calcium oxalate and calcium phosphate supersaturations matter to you. This kind of stone is often made by calcium oxalate growing over an anchor of calcium phosphate on the inner surfaces of renal papillae. Sometimes, it appears that these stones might form on the ends of calcium phosphate plugs in the terminal portions of the kidney’s tubules – where the final urine leaves the kidneys. If you have calcium phosphate stones, calcium phosphate supersaturation matters most, but sometimes there is also considerable calcium oxalate so both may matter.
If you have uric acid or cystine stones, it is those supersaturations that matter most.
Here we will consider only the two calcium stones, leaving uric acid and cystine for another time.
WATER DEMANDS VARY OVER THE DAY
The Big Picture
The featured image at the top of the post tells the story for calcium oxalate and calcium phosphate. Cystine and uric acid are special cases we cannot cover here but will in later posts.
Likewise, our work here is really about stone formers without a systemic disease as a cause of stones. Systemic disease pose their own limitations and special problems which we do not consider here.
Some patients who form stones have other diseases that are not causes of stones but affect whether high volumes of fluids are safe. Examples are heart failure, chronic kidney disease, chronic liver disease, malignant tumors, and the need for medications that alter the balance of salts and water such as diuretics and innumerable psychoactive drugs for, as examples, depression, anxiety, and seizures. This list is not complete. Physicians determine safety in this complex matter.
How To Read The Featured Image
We show urine supersaturation along the vertical axis as a ratio. The dashed horizontal line at 1 is solubility – crystals will not form or grow. Below 1 is undersaturated: more could be dissolved. Above 1 is supersaturation: crystals can form or grow. Values for calcium oxalate are on the top row, those for calcium phosphate on the lower row.
The urine flow rate runs horizontally along the bottom axis. The units are milliliters per hour; 1000 milliliters make up a standard 1 liter water bottle. A liter is 33.8 ounces, just slightly more than a quart (32 ounces). So 100 milliliters (where we put the dashed upright line) would be 1/10 liter, or about 3.4 ounces per hour of urine flow. If you calculate what that would be in a 24 hour day, it is 2.4 liters (or quarts) a day.
What Are Our Supersaturation Goals?
Obviously, supersaturation falls as urine volume goes up. That is what we expect from all we have written up to this point. But how low do we need to be, and why?
We Have No Trials
Given the effects of crystal modulating molecules in urine and the complexity of how crystals actually form in or on kidney tissues we cannot state a priori some supersaturation will be ‘safe’ except if below 1, and that is hardly reachable for calcium oxalate and not always so for calcium phosphate. No trial data associate levels of supersaturation with kidney stone recurrence.
We Have a Principle
If new stones are forming, and the urine studies are obtained under conditions that reflect everyday life, the supersaturation is presumed to be too high for that person and should be lower. As an arbitrary value, Dr. John Asplin, who first enunciated this principle for us, offers lowering it by half. Crudely put, this makes an average goal around 5 or less for calcium oxalate, and about 1 or less for calcium phosphate, given the average levels of supersaturation observed before treatment.
The left panels show kidney stone formers (red) and normal people before breakfast, which means fasting since the night before.
Almost all the urine samples are supersaturated with respect to calcium oxalate (upper panel; most of the points are above the horizontal dashed line at 1). Below 100 ml/hr (3.4 ounces/hour) supersaturations rise steeply.
By contrast, many of the urines were undersaturated (below the dashed line at 1) with respect to calcium phosphate (lower left panel). Even so, below 100 ml/minute, the percentage rises steeply.
Stone formers (red points) have higher supersaturations than normal people (blue points) for the reasons we already mentioned: They tend to lose more calcium, or oxalate, or less citrate (a molecule that protects against stones) in their urines than normal people, so for any amount of urine their supersaturations are higher.
The message to patients and their physicians: Keep urine flow above 3.4 ounces an hour between arising and breakfast; for safety, plan for 4 or more ounces an hour.
As noted in the review of the Pak experiment (below), the difference between 24 hour urine volume and actual fluid intake is about 0.9 liters (900 milliliters), or 37.5 milliliters (1.1 ounces) per hour. Rounding, to avoid confusion, we need 4 ounces of urine or 4+1 = 5 ounces of fluids an hour.
Urine calcium losses, especially, but also losses of oxalate rise more with meals in stone formers than in normal people, which creates a need for even more water than is needed while fasting. The middle panels show the consequences. While fasting, 3.4 ounces per hour will keep supersaturations below 1 for calcium phosphate and below 5 or so for calcium oxalate. Fed, it takes roughly 125 ml/hour (4.25 ounces/hour). We have proposed this point – supersaturation below 5 – as a reasonable basis for estimating an appropriate fluid requirement. Given the extrarenal water losses mentioned about of about an ounce an hour, this comes to 4.25 + 1 ounces an hour, or about 5.25 ounces an hour.
Fortunately we tend to like fluids while eating, and the graphs make clear that lots of people were drinking even 10 ounces of fluids per hour. By fed we mean the whole period from breakfast through bedtime, about 14 hours.
Almost no one exceeded 100 ml/hr (3.4 ounces/hour), but like the other periods urine flows below that point were on the steep rise of supersaturations (right upper and lower panels). Urine losses of calcium fall over night, but a lot less in patients than in normal people. So, like for fasting, about 5 ounces per hour would be about right.
The Grand Totals
People all live their own lives and many, perhaps most, deviate from the 2 hour fasting, 14 hour fed, 8 hour overnight schedule we used for this research. So we can total up all the fluids needed in our example as an example which can be modified for any individual person.
Fasting, 2 hours, at 5 ounces an hour, 10.5 ounces (0.3 liter) total.
Fed, 14 hours from first meal to bedtime, we need 14 * 5.25 = 73 ounces (2.1 liters) total.
Overnight, 8 hours, at 5 ounces an hour, 40 ounces (1.2 liters) total.
Altogether this makes 123 ounces (3.6 liters) of fluid intake a day in this example. One can calculate for the fasting, fed, and overnight periods of a patient to obtain a more refined estimate.
A VIEW FROM 24 HOUR URINES
In 1994 Professor Jacob Lemann produced this image which we do not believe he published. He gave it to one of us (EW) and we place it here as a valuable counterpoint to our figure. He collected 24 hour urine samples from 94 normal adults and 45 calcium stone formers not otherwise characterized.
We have his data for only calcium oxalate supersaturation, shown along the vertical axis. The horizontal axis shows urine volume in liters per 24 hours. EQUIL, the program he used to calculate supersaturation, is the same one we used.
The image is below our usual standard because we do not have an original. We cannot correct the lost numbers on the vertical axis, for example.
From his graph, to bring supersaturation in patients below 5 would require about 2.2 liters/day, which is not very different from what we calculated from the different periods 2.75 liters. Given the estimate of an extra 900 ml/day of losses this comes to 3.2 liters or 108 ounces.
Because the 24 hour urine smooths out peaks – and valleys – and because schedules differ among people, the correspondence is surprisingly good.
AN EXPERIMENT OF CONSIDERABLE VALUE
An Important Difference
In 1980 our friends and colleagues Dr. Charles Pak and Kashayar Sakhaee performed a lovely experiment in which they varied urine volume in people and measured saturation. We and Jack Lemann observed: People ate or not in our CRC setting, or they collected 24 hour urines as they went about their days. But Charles and Kashayar altered the urine volume specifically, so they could relate a deliberate change in volume to a resulting change in saturation and, importantly, relate fluid intake to urine volume.
What They Found
Their measurements of saturation differed from most we have presented in being direct, not calculated. They incubated samples of urine with an excess of the solid phases – calcium oxalate, and calcium phosphate in the form of brushite – so as to bring the sample to the solubility point. The ratio of the product of the calcium and oxalate ion activities (calcium oxalate) or calcium and hydrogen phosphate activities (calcium phosphate) before to that after the incubation is like the supersaturations we present. But their values in a given urine at solubility is determined for each sample and not estimated from equations. They called this ratio the activity product ratio, or APR.
Effects on Saturation
We have copied their figure with its original caption which explains it perfectly. As they increased urine volume in their subjects, supersaturation fell. At about 2.5 liters, that for calcium phosphate (Br) was at solubility (the line at 1) and that for calcium oxalate (CaOx) was about 2. The stars give estimates of the significance of the fall.
Our detailed review of supersaturation presents three zones: undersaturated; metastable supersaturation – like most urine; and unstable supersaturation – where crystals are forming and the energy of the solution is running down. The formation product ratio is the activity product ratio (their estimate of supersaturation) at which the urines they studied enter the unstable zone.
For calcium phosphate that zone is about 4 – 5 and is unaffected by volume. For calcium oxalate it is a lot higher, and rises with water. So the protective effect of diluting the urine seems greater for calcium oxalate: the floor – saturation – goes down while the ceiling – formation product – goes up.
These formation produces could cause some confusion. They are essentially the Ostwald limits I have written about elsewhere.
How Much Do We Drink?
In their text they give some remarkable information: 1.8 liters of intake gave 1.02 liters of urine; 2.3 liters gave 1.35 liters of urine; 2.8 liters gave 1.88 liters of urine and 3.3 liters gave 2.38 liters of urine, Differences between intake and urine were 0.78, 0.95, 0.92, and 0.92 liters/day. This means that to get the highest protection they observed, we would need to 3.3 liters (112 ounces) of fluid a day. This corresponds well with estimates of good protection from our work and the Jack Lemann data.
HOW TO PRESCRIBE
A Standard Estimate
Because we have no trials, we cannot say that calculations based on our data will yield better results than just an overall 24 hour goal. But there seems to risk to doing the simple arithmetic: 100 ml/hour fasting and overnight, 125 ml.hour from breakfast to bedtime. This would be a kind of standard estimate which can be varied depending on the circumstances.
Alternative Estimates of Supersaturation Goals
We have already pointed out that because of the many crystallization modifying proteins in urine one cannot say a particular supersaturation is ‘low enough’ in general. Many normal people have high urine supersaturations as in the 24 hour urine and featured graph, but do not form stones. Very many stone formers have urine supersaturations that overlap with those of normal people.
Activity of Stone Formation
For this reason, we have proposed on this site that the supersaturation of an active stone former is too high. Active means that new stones are forming as opposed to passage of stones what were present in the kidneys in the past. A reasonable goal is to lower the supersaturation by half regardless of its absolute value.
Using this criterion, many people on our graphs who were actively forming stones when we or Lemann or Pak made their measurements would have to lower supersaturation for calcium oxalate well below 5 – those with supersaturations of less than 10 for calcium oxalate. This would require more fluids than in our standard estimate.
Other Treatments Beside Fluids
Throughout we have treated supersaturation as if it could be lowered only through increase of urine volume. But of course there are other treatments, and they would in general reduce the need for fluids.
Such treatments lower urine calcium, or oxalate, or raise urine citrate. We have alluded to citrate but are not as yet ready to introduce the full story at this early stage of this site. But raising citrate is also an important means for reducing supersaturation.
Even so, fluids exactly reverse the renal process that produces a supersaturated urine. They are safe in most patients. They have about them as a treatment what we might call elegance – a simple and effective means of accomplishing a goal.
Other worlds Beside Those of These Studies
The value of 0.9 liters for daily non-renal fluid losses is not applicable in all cases. The world has deserts in it, people who build buildings outdoors in summertime, workers in kitchens and foundries, workout enthusiasts, professional athletes; none of these will match the 0.9 figure. Even the seasons matter, and sex, too. Men lower their urine volumes and raise supersaturations greatly in summer time, women do not. Judgment is needed here.
HOW TO USE OUR OTHER POSTS ON FLUIDS
We have offered several posts on tricks for drinking more fluids, and how to make good choices of beverages. The goal volumes for these posts are much higher than those considered here. The reason is that some people will need such large volumes to lower their supersaturations by half – those people who are active stone formers even at relatively low urine supersaturations. The two other posts are meant, therefore, as upper limits from which one can scale back as needed.