Phenotype is a medical term physicians use to identify groups of patients who share diagnoses and treatments in common. Although every kidney stone former has unique traits that need attention, they can be grouped into phenotypes for which certain general treatment approaches have been tried and found valuable. Within those general approaches refined treatment answers to those unique details particular to a given patient.
When successful, the process of this chapter grants you a name. That name sums up where you fit in as a type of patient. Because patients within a given type have in common causes of stones, treatments and trials, and long term outlooks – so called prognoses you want to know where you fit in. That name is the name of your phenotype, your community of stone forming patients.
If you successfully negotiate the work here, you will get your name.
I assume you already read Chapter Three. If you did not, please read it before going on. I say this because otherwise what I will now say could seem confusing and obscure.
I cannot tell if the angel had an unlimited vocabulary from which to choose, or perhaps only one name. But medicine has a modest number for stone formers.
The names are compounds. Part of the name will include the type of stone. Part will include the presumed causes of stones. Together they will assign you to a ‘phenotype‘, a group of people enough like you that their treatments, and the outcomes of their treatments can predict what is best for you.
Think about it.Suppose you want to conduct a treatment trial. You gather patients together who are like one another and treat half one way the other half perhaps not at all, or in some other way.
Who are these patients?
They must be of a recognizable type, of phenotype, so you can transfer the results to other patients afterwards who are like those you studied.
What Are Phenotypes?
The word was first used in 1909, a combination of the Greek Phainein (to appear) and Type. Both the Mosby and American Heritage Medical Dictionaries define it is the observable characteristics of (in our case) a patient as determined by genetic makeup and environmental influences. Mosby offers a secondary definition of simply organisms (patients in our case) that resemble each other in appearance.
Our problem here is to consider the meaning and utility of phenotype in relation to kidney stone disease.
By Stone Type
There are calcium oxalate, calcium phosphate, brushite, uric acid, cystine and struvite stones to consider, along with drug stones. So your name will certainly include one of these as well as the dreaded ‘stones of unknown type’.
Because each stone type really does point to reasonably well defined causes, treatments, and long term outlooks – prognosis – this part of the name, your stone phenotype, works.
A large fraction of risk factors that cause kidney stones, like high urine calcium or oxalate, low urine citrate, or too high or low a urine pH simply are found in patients without an obvious cause. Their causes remain an occasion for more research. We call them idiopathic, meaning they arise within the person as a characteristic of that person but their origin remains unknown.
Some arise from named diseases like primary hyperparathyroidism, renal tubular acidosis, or one or more bowel diseases. Each of these disease has its own phenotypes and in some cases genotypes – pattern of gene variations.
Finally, although relatively rare, genetic diseases cause stones. Their definitions arise directly from the abnormal genes involved. Unlike outcomes of normal gene variability, these are usually evident abnormalities of genes that can be detected by sequencing DNA.
By Kidney Mineral Deposit
We distinguish nephrocalcinosis, medullary sponge kidney, and staghorn stones as meaning having to help define a phenotype. New digital instruments visualize papillae during stone surgery so we can now speak about plaque and plugging as at least present or not. In some centers urologists make crude judgments about abundances of both. Likewise with these instruments urologists can distinguish stones from nephrocalcinosis and medullary sponge kidney. Radiographs cannot do this well.
They Act Through Supersaturation
Whatever the cause, kidney deposits and stones can be produced only by supersaturation with respect to the crystals. These supersaturations rarely make it into the phenotype even though only they can produce the very crystals that we care about and want to prevent.
Because citrate, acts through inhibition of crystal formation and growth, low urine citrate can cause stones. Everyone eyes with glum suspicion the myriads of urine proteins that influence crystal formation. But no one has yet fingered even one as a culprit.
Here we are. You will fit somewhere. When you find your place this site and you will link in a new way.
Idiopathic Calcium Stone Former (ICSF)
The first term means suffering from yourself – idios + pathos. therefore your genes and behavior are the formal cause of stones. Their material cause is calcium crystals.
If this is you, much of the site is about you for you are the commonest of all stone formers. All of the trials concern you. You might have noticed that the large left margin table of contents for the site mainly concerns idiopathic calcium stone formers.
ICSF can form calcium oxalate, hydroxyapatite, and brushite kidney crystals, often admixed. So how do we distinguish people into their types?
We work by abundances. Above fifty percent calcium oxalate in the average of all stones and absence of brushite we name as idiopathic calcium oxalate stone formers. Above 50 percent hydroxyapatite and no brushite we name as idiopathic calcium phosphate stone formers. Any brushite in any stone is enough to name an idiopathic brushite stone former.
You are in Chapter Five, and at this point you are free to leave here and read about yourself there.
Uric Acid Stone Former (UASF)
As yet I have no article devoted to them, but simple increase of urine pH prevents almost all uric acid crystallization in urine. I like to think about uric acid in stones as enough to label a patient as being – at least in part – a uric acid stone former because that uric acid points to an excessively acidic urine and a need to use supplemental alkali.
Cystine Stone Former
These patients nearly always have cystinuria, an inherited disorder of kidney cell amino acid transport. They require special care. This article concerns them.
Struvite Stone Former
Struvite in human kidneys arises from the action of bacteria that hydrolyse urea to ammonia. Being infected foreign bodies they require surgical management. Like uric acid, struvite can be part of other stones and arise because calcium stones, as an example, become infected.
Primary Hyperparathyroidism (PHPT)
This systemic disease arises from over activity of one or more of the parathyroid glands in the neck. One of many manifestations is calcium kidney stones. The disease is diagnosed by combined blood and urine measurements obtained during the initial evaluation of a stone formers. Sometimes PHPT emerges during treatment of an ICSF who has harbored PHPT in a dormant form. You are in this long article.
Renal Tubular Acidosis
This is a group of genetic and acquired diseases of the kidneys that render them incapable of lowering urine pH normally. They produce calcium phosphate stones because high pH raises calcium phosphate supersaturation. Tubule plugging with hydroxyapatite can be so extensive as to damage kidney papillae and the medulla, and chronic kidney disease and even end stage kidney failure occur in some people. No articles on this site as yet concern this phenotype.
A group of inherited liver diseases that produce excessive amounts of oxalate. The oxalate is mainly excreted by the kidneys and produces terrible tubule plugging with calcium oxalate crystals. The crystals involve not only the papillae and medulla but the cortical tubules and therefore can cause acute and chronic kidney disease and a need for transplantation or dialysis in some cases. No articles on this site as yet concern this phenotype.
Small Bowel Malabsorption
Almost any disease that causes delivery into colon of undigested small bowel effluent can promote excessive oxalate absorption in colon. The result is much like that of primary hyperoxaluria but not identical. The amounts of urine oxalate usually are less, but at the same time urine volumes can be much lower than normal because of bowel disease. Calcium oxalate stones are usual but tubules plug not with calcium oxalate but rather mainly with calcium phosphates. Kidney disease and kidney failure can occur but much less frequently than with primary hyperoxaluria. No articles on this site as yet concern this phenotype.
Obesity Bowel Surgery
These are a group of surgically induced small bowel malabsorption disorders designed to produce weight loss. The procedures raise risk of stones but newer ones appear safer and less likely to raise urine oxalate compared to earlier procedures. No articles on this site as yet concern this phenotype.
Loss of colon causes severe reductions of urine volume, alkali losses that create very acid urine pH values, and therefore a mixture of calcium oxalate and uric acid stones. Because the colon is absent urine oxalate is not elevated even if ileostomy coexists with small bowel malabsorption. No articles on this site as yet concern this phenotype.