The crystals of the common kidney stones
I suppose I could have made my pie chart smaller but I wanted it to shine out like some odd colored moon because the names of the stones are so important and so much of what we do depends upon knowing them. They names of kidney stones are the names of the crystals which make up the hard part of the stones: CAOX, Calcium Oxalate; CAP, Calcium phosphate; UA, Uric Acid; Cystine; Struvite. The pie wedges show their relative abundances to each other in our large population of stone forming patients. Calcium oxalate stones are the most common by a wide margin, and that has been true in every accounting of stone types I have ever seen.
The whole science of stone prevention focuses upon stone crystals. Each type of crystal creates its own unique illness and has specific details of treatment. That is why we name the stones by the names of the crystals they contain and why when stones are analysed the results are listed by these very same names. Being a bold and rather large graphic, the picture does what I intended, brings the main facts into view as, at a circus, the great animals and the small animals circle the ring by way of an introduction. Come. I will show you all the common stones, like at a fashion show, or a circus parade. You can watch as they go by and remind yourself, or wonder, which ones might have been yours. Here they are.
Which ones do you have?
Or, better put, which ones did you once have before effective treatment? I cannot help repeating myself. You might think your doctors know what kinds of stones you have formed, but don’t rely on it. People move, doctors move, health records are far from ‘all electronic’. That stone report from 4 years ago could be in a dusty filing cabinet and your new doctors unaware it exists. Worse, it could be in a dresser drawer and you forgot it you put it there. Perhaps even more worse, the stones might be in that drawer and never analysed at all.
But if there are no analyses, or they are lost, treatment remains perfectly possible; it is just less focused and therefore possibly less effective than when guided by a knowledge of the crystals. So always seek treatment. If a stone comes along the way, make every effort to get an analysis made of it.
Why should you care to know all this?
I would say an informed patient can best participate in his or her own treatment. Because stones are often chronic, their prevention depends upon a willingness to maintain treatments over long periods, treatments which ultimately work by altering urine chemistry in a direction which minimizes the risk of forming crystals. Just as the sailor who aims along a chosen track against the random, misdirecting, and confusing winds and currents maintains a constant way in proportion to that skill which comes from knowing the way of the boat, patients who aim to keep a certain kind of condition in their urine despite the demands and temptations of the world do so, I believe, in proportion to that skill which comes from knowing how their work and lives and foods affect their own bodies, and how those crystals form which they so much desire to prevent. Put another way, knowledge is power.
This post is a lot longer than most because I wanted to put all five main stone types together. There is no reason to read it all at once or even all of it. Your stones are just one part and perhaps that is all you will care to read about. It will always be on the site as a reference if you need it.
I should mention here, to save a lot of confusion, that in the real world you live in stones often contain mixtures of crystals. The pie chart refers to the most common crystals in a stone, for which the stone is usually named. Much of the time, minor crystal components are not crucial, but sometimes – to jump forward a bit – they are. Even a trace of struvite or cystine, for example, can have great diagnostic importance.
Calcium Oxalate Stones.
In the great circle of stones atop this page, the calcium oxalate stone occupies a lion’s share of the space. It is the common stone, what the majority of people form. Its crystals are formed through the combining of calcium and oxalic acid. Calcium is simply an abundant urine atom. Oxalic acid, a dead end waste product that the kidneys remove, is made of two carbon and four oxygen atoms.The oxygen atoms in this simple line drawing of its structure are at the two corners where the oxygen atoms (circles) attach. The lines from the corners to the oxygen atoms are a shorthand meaning the carbon atoms, which are not marked, are bonded to the oxygen atoms in a manner that will not easily come apart. Likewise the line between the two carbon atoms means they are bonded together.
Oxalic acid is a rather strong acid and so, at the acidity of urine, it exists as a charged ion – oxalate – which has 2 negative charges. (I will write about ions later. It is the name for a solitary charged oxalic acid molecule as it exists in water and this public reference is fine for the moment). Calcium atoms carry two positive electrical charge. Broadly speaking – though my more expert colleagues may bridle at such a simplification – the calcium and oxalate combine by an attraction of their matching and opposite charges.
The stones are generally not too big, between 1 and 10 mm and most of those less than 7 mm will pass without need of surgery or lithotripsy if they move from the kidney to the ureter, the tube that connects the kidney to the bladder. The kidneys themselves are not obviously injured except when obstruction lasts too long, or something happens during surgery. The causes of calcium oxalate stones are numerous enough to command multiple chapters of a standard reference textbook and it is to their prevention that physicians turn their major attentions.
Sometimes these stones arise as part of a systemic disease. A common example is bowel disease. It is the job of physicians to discover systemic diseases as a cause of stones, or establish that a known disease – like bowel disease – is the actual cause of stones Patients cannot do much for themselves in this area except provide as complete a medical record as possible.
But most of the time these stones are not due to a systemic disease but to the interplay between inheritance, diet, and aspects of daily living. When changes in daily living are key parts of treatment, it is patients themselves who must create and maintain those changes even though it is physicians who discover the links between daily living and stone production, and select those changes which can prevent new stones. I believe patients can so this in proportion to how well they understand what is needed, and why.
Medications are meant to be added when changes in daily life are not enough. Several have been tested in randomized trials, the gold standard. But benefits from changes in daily living almost always add to those from medications, so in all cases patients are active therapists for their own disease.
The calcium oxalate stones come in two varieties, calcium oxalate monohydrate and calcium oxalate dihydrate. The former are harder and therefore more resistant to fragmentation by lithotripsy. LIkewise, the former appear more often when elevated levels of urine oxalate are present.
Calcium phosphate Stones.
Less common, calcium phosphate stone crystals are calcium atoms combined with phosphoric instead of oxalic acid. Phosphoric acid is simply a phosphorus atom (shown as the ‘P’ in the line drawing to the left) with 4 oxygen atoms bonded to it. One of them has two lines for its bonds; this oxygen cannot provide any charge with which to bond calcium atoms to make a crystal. The other three have ordinary bonds that are shown by a line, and a dashed and solid arrow. These two arrows mean simply that the oxygens lie above and below the plane of the paper – so if you built the molecule with sticks and balls it would have a three dimensional shape. One of the three negatively charged oxygens never has a hydrogen on it in urine but only when the solution is exceedingly acidic. A second charged oxygen is always occupied by a hydrogen atom in urine. The third oxygen is variably occupied by a hydrogen in urine so phosphate ion has one or two charged oxygens with which to bind calcium. In a urine of average normal acidity, it has mostly one, not two negative charges, so it does not readily combine with calcium by charge attraction. When the urine is abnormally alkaline, the variable oxygen becomes charged so the ion has two negative charges which can combine with calcium to make crystals. For this reason calcium phosphate stones tend to occur in people who produce a more alkaline urine than those who produce calcium oxalate stones.
Let me say here it is in fact a very complex process, this combining of charged ions, one which I will try to explicate in later posts. But for the moment what I have said is not untrue and has the advantage of a stark and simple outline. In accord with such simplicity I shall simply mention that the calcium phosphate stones are of two forms, each a different type of crystal that calcium and phosphate can make together: Brushite, which is an equal mixture of calcium and phosphate ions, and hydroxyapatite, which has more unbalanced proportions of calcium and phosphate. The latter is the mineral that makes bones hard.
Sometime I shall tell you about brushite and hydroxyapatite and their varied fates. How the one precedes the other only to be consumed. How crystals cannibalize one another in their fight to survive. How the organic molecules in urine modify their actions one to another. In other words, as time goes on I will tell you about the underlying complexity of this disease which manifests itself as common stones.
But in the mean time it is enough to say that people with calcium phosphate stones have more numerous and often larger stones than people with calcium oxalate stones. Brushite stones are very hard and do not break well with shock wave treatments. Hydroxyapatite crystals can plug the kidney tubules and injure kidney cells. For these reasons, prevention may be more urgent than for calcium oxalate stones. But I say ‘may’ as we do not as yet have evidence that this is true. Because diet and lifestyle changes are often not enough for prevention, medications are commonly needed.
Uric Acid stones.
Although about as common as calcium phosphate stones, uric acid stones are altogether different. They are made of crystals of uric acid, a breakdown product of DNA and RNA, which form when urine is too acidic. The stones can be red or orange because uric acid crystals absorb hemoglobin breakdown products that are red – orange pigments in urine. Sometimes uric acid crystals pass in urine as a red orange gravel.
Acidic urine is common in obese and diabetic people, and in those with gout or kidney disease. How the urine becomes acid is known, and perhaps a topic we will cover here. How the crystals form is easy to say but brings up a new idea. The molecule of uric acid is organic, meaning it is composed of carbon atoms strung together, in this case in the shape of two linked rings. That the material is in urine, and that it leaves the urine to form crystals when the urine is acidic introduces the question of that it means for something to be in urine in the first place. And, because, after all, stone disease is about things that are in urine leaving the urine in a solid crystalline form, we might as well face the reality of those ideas now as opposed to later.
Water molecules are each a single oxygen atom (large ball) bonded with two hydrogen atoms (small balls) as in this picture from Wikipedia. The hydrogen side has a positive, the bare side of the oxygen a negative charge. So water molecules link to each other, positives to negative surfaces, to make up the clear and seemingly continuous fluid we drink, swim in, and hold up umbrellas to keep off of us when it rains. They link by charge at angles, shown by the number ‘1’ so as to make up a three dimensional macrame. To be ‘in solution’ means to have some charge to which water molecules can link up with by attraction. Calcium atoms are positive and become surrounded by a shell of water molecules facing it with their bare negative surfaces. Oxalic and phosphoric acids have negative charges and are surrounded by water molecules pointing their positive or hydrogen sides to them.
Uric acid, the molecule we are interested in here (shown to the far right), is made of carbon atoms arranged in rings (they are at the angles where lines join), with interposed nitrogen (N), oxygen (O), and hydrogen (H) atoms. There is very little charge in this molecule as it exists in normal urine except at the nitrogen at the bottom of the larger 6 sided ring on the right side of this drawing. When urine is of normal acidity, the hydrogen atom leaves the nitrogen which then has a negative charge to which water molecules can relate. Think about this; the whole huge molecule – it is so much bigger than a calcium atom, or even an oxalate molecule which has only 2 carbon atoms – and yet has only one small site that can ‘hold’ it in the water. When that site has its hydrogen atom on it, water has so hold on the molecule it simply leaves the water as water droplets form in the high and vaporous late afternoon clouds, and fall from the air as the warm rains of springtime.
Because there is much more uric acid in urine than there is oxalic acid, uric acid stones can become very large, even enough to fill up the entire collecting system of the kidney. Because uric acid does not have to connect itself to some other atom or molecule to make a crystal, in the way that calcium must bond with oxalate or phosphate ions to make crystals of calcium oxalate or calcium phosphate, crystals of uric acid can form very fast, in seconds, and pass as an orange gravel in the urine. If retained, such crystals can grow rapidly into large stones.
But because the whole process depends almost completely on the acidity of the urine, uric acid stones are very easy to treat. Just a modest amount of supplemental alkali will make the urine of almost any patient alkaline enough that the hydrogen atoms are removed from the one crucial charged nitrogen, and water can bond there so uric acid remains in solution. Being so simple to obtain, there is little reason to expect new stones once the stone type is known to be uric acid.
Unfortunately, however, uric acid may be only part of a stone problem, as it is commonly mixed with calcium oxalate. In this case, one needs to track down the cause of the calcium oxalate stones as well as to make the urine more alkaline in order to stop all stones from forming. It is rare to find uric acid mixed with calcium phosphate crystals, because I have already pointed out that it takes a rather alkaline urine to remove the hydrogen atoms from phosphate so it has two negative charges and can bind efficiently with calcium atoms.
Struvite crystals are made of the triple combination of magnesium, ammonium, and phosphate. The kidneys cannot themselves make such crystals; they are made by bacteria. Essentially, bacteria which are essential to the great nitrogen cycle of the planet find their way into some of us, and in doing what benefits our whole living world cause great harm in the confines of an individual urinary system.
Like oxygen, nitrogen is an essential for life yet dangerous. It is integral to proteins, DNA and RNA. As these molecules are broken down and remade, some of their nitrogen slips by and can form poisonous compounds unless caught up in safe waste products. One of these is uric acid, which contains 4 nitrogen atoms (look back at the picture of it) and is excreted in the urine. The other main one is urea which contains 2 nitrogen atoms bound to a single carbon atom (‘C’ in the picture to your left). . Birds and reptiles excrete most of their nitrogen as uric acid; mammals like us excrete it mainly as urea.
As the animals of the world urinate on to the soil, their urea recycles lost nitrogen to where plants have their roots, but plants cannot use urea, they cannot break it down to release the nitrogen from the carbon atom which holds them. The bacteria that make struvite crystals normally grow in soil and have an enzyme called urease which can break down urea into ammonia. which plants use as their nitrogen supply. The soil bacteria are thus essential for the nitrogen cycle of the earth. But though on the earth, our kidneys are not the earth or the soil. Urine is filled with urea, and if the soil bacteria get into the urinary tract they break it down to ammonia. The ammonia makes the urine around the bacteria extremely alkaline, and the ammonia crystallizes with magnesium and phosphate that are always in urine to make struvite.
You might wonder how soil bacteria can get into the urinary system. We eat them with foods that are not cooked, and mostly they become part of the intestinal bacterial population from an early age. So they are around us and can find they way into the urinary system, especially in women whose shorter urethra makes entry easier. No matter how skillfully used, any instrument put into the bladder can carry our personal soil bacteria with it. Because they live among molds and fungi soil bacteria easily mount resistances to antibiotics, so antibiotics given for a urinary tract infection will tend to kill sensitive bacteria and select out those that can resist them.
Soil bacteria can produce struvite stones de novo, or infect calcium stones to produce a mixed stone. Either way, struvite stones are infected by their very nature. They can become huge, and their bacteria can injure the kidneys, even enter the bloodstream and cause sepsis. Treatment is a mix of thoughtful and skilled surgery and selection of antibiotics after such surgery to kill bacteria that remain. If the stones are a mixture of struvite and calcium crystals, new calcium stones need to be prevented.
Lemon yellow with a sugary coating these form only in people who have an inherited kidney disorder called cystinuria. The kidneys function well except that they permit abnormal amounts of four amino acids to enter the urine. Three do not matter that we know of. The fourth makes crystals and stones.
Cystine, as the picture on the left shows, forms through the coupling of two identical units through their sulfur atoms (‘S’ in the line drawing). Each of the two units contains two carbon atoms – as usual not shown except at the corners. Just like oxalic acid, the two carbon atoms are bonded together (shown by the single long line that connects the two corners). One carbon atom has 2 oxygens bonded to it; the other has one nitrogen (which makes it an amino – nitrogen containing – acid), a hydrogen atom, and a sulfur atom. As for phosphate, the dashed and solid arrows simply mean the hydrogens and sulfurs lie above and below the plane of the page and a stick model would have a three dimensional shape. Each unit is called ‘cysteine’; the pair is cystine.
Cysteine itself is very soluble because the sulfur atom has an appreciable negative charge. But the big, long cystine molecule has very little charge on it because the hydrogens do not come off of their oxygens in urine to any appreciable extent. The main charge is at the sulfur linkage but it is much less than when the sulfurs are not connected to each other as is the case for cysteine. So, like uric acid, cystine readily loses intimacy with water molecules and simply leaves the solution as crystals. The process is fast, and in people who lose the amino acid in their urine because of cystinuria the amount of material available to make stones is large, so stone growth can be rapid.
Like uric acid and struvite, cystine stones can become very large. Like phosphate stones their crystals often block kidney tubules and can damage their cells. Stones may begin in childhood.
Treatment is very effective but almost always requires very large amounts of fluids to dilute the urine. The few drugs that help prevent them have side effects so fluids are always the foundation of treatment.
I do not intend a catalog here, simply the point that here and there we find patients who are making uncommon crystals and require very special care. Uric acid, as an example, can form odd crystals such sodium or ammonium acid urate, especially in people with bowel disease and chronic diarrhea. Anti-viral drugs, especially, can crystallize in urine and form stones which are not always recognized for what they are except through stone analysis. Very rare disorders of metabolism can produce molecules which crystallize in the urine; I mention 2-8 dihydroxyadenine as an example. Stone analyses will put physicians on the right track for these special cases, although it is often a while before the right answer emerges.
The end of a very long post
That’s my parade. The common animals and the rarer animals have gone by, and you have glimpsed the main ones, big and small. The one point is what it was at the beginning. Each kind of stone crystal has its own ways, and treatment requires we know which one you have. Likewise, for whatever that one may be, it is good to know as much about it as you can know, for long term prevention of stones is hard to come by and ultimately the limit is often the patience and will and consistency of patients themselves that matters most.
Track down old reports and pull them together.
Keep copies and send everything to the doctors who care for you.
Fred Coe MD
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