Except for the cystine crystals and a few others, the majority
of crystals found in the urinary sediment are of limited clinical
value. It is tempting to associate crystals with a risk of
urolithiasis, but the majority of patients with a crystalluria do
not have and will not develop kidney stones. Many benign
situations can provoke crystal formation.
In the majority of cases, the crystals found in urine are not
present in the freshly voided specimen. Alkalization and
refrigeration are promoters of crystals formation.
The interpretation of a persistent crystalluria must be
done according to the clinic.
Drug crystals are sometimes found in urine. In most cases,
these findings are of little clinical value except, if the
sediment's picture indicates a possible renal obstruction.
Crystal casts are pathognomonic of this situation.
Some think that giving much time to the identification of unusual
crystals is not worthwhile.
Crystals related to urolithiasis are, except for cystine, usual
and easy to identify. Calcium is found in 80 to 95% of kidney
stones, mostly as oxalate or phosphate crystals. Many stones are
not homogeneous. Some have a nucleus of a different composition
from the surrounding matrix. The following table shows stones
composition listed by occurrence.
Urolithiase composition and occurence
||Occurence in %
Calcium hydrogen phosphate (Brushite)
Tri-calcium phosphate ( Whitlockite )
|Triple phosphates (Magnesium
ammonium phosphate) (Struvite)
||5 to 10
In many cases, the presence of crystals is a pest to the
The elimination of these crystals can be made by gently
heating the specimen at 37°C. To attain complete dissolution, it
is preferable to heat the whole specimen. Once decanted, it is
often impossible to dissolve the bulk in the small remaining
It is possible to dissolve the obscuring crystals by adjusting
the pH. Phosphates can be dissolved by adding a drop or two of 2%
acetic acid. Amorphous urates can be dissolved by adding an
alkali like a 2% ammonia solution. But heating is by far a
preferred method. It is not wise to solve a urate problem by
creating a phosphate precipitation.
It is impossible to dissolve the quantity of calcium,
phosphate, and oxalate eliminated in a 24-hours urine specimen
into 1 to 2 liters of water. It is therefore necessary to
conclude that substances inhibiting the crystallization are
present. Known inhibitors of urinary crystallization are
pyrophosphate, citrate, magnesium, and certain macromolecules.
The Tamm-Horsfall protein is
believed to be an important calcium oxalate inhibitor. This role
is thought to be due to the sialic acid residue of the protein.
While the fully sialated protein is an inhibitor, the sialic
residues lacking protein is a crystallization promoter.
Urine is a supersaturated solution of calcium, phosphate and oxalate in equilibria.
Crystal formation can be caused:
- by an augmentation of concentration beyond the
supersaturation capacity. This situation is mostly
the result of a decreased dilution like in a case of
insufficient water intake. The situation could also be
caused by a high elimination.
- by a decreased supersaturation capacity. This
situation could be caused by a decrease in inhibitors
concentration, a neutralization of these inhibitors, by
some electrolytes, or a by pH change.
- by the presence of crystals with a promoter effect on
the crystallization of another species. Crystallization of calcium oxalate promoted by amorphous
urates is a good example of this phenomenon. This
situation is thought to be the result of a competition
for the inhibitor site of Tamm-Horsfall protein. Urates
an calcium oxalates adhering to mucus is a frequent
Some crystals are found exclusively in acid urine, others
are found exclusively in alkaline urine.
Amorphous crystals are often identified on the basis of the
urine pH. In an acid specimen, urates are reported, in an
alkaline specimen, amorphous phospate are reported. This
simplification should be used with care. Amorphous phosphates and
triple phosphates are sometimes observed in slightly acid
specimens. (pH 6,5)
The usual crystals found in urine
Specific clinical conditions that explain urolithiase
formation can also explain a persistent crystalluria.
An increased urinary calcium elimination can result in a
crystalluria, mostly as calcium oxalates. The superior limit for
the calciuria is 75 mmol/d under a 250 mmol/d diet.
Hypercalciuria can be caused by:
- an increase of the fraction of the diet absorbed.
- a renal loss with a secondary increase in intestinal
- an excessive bone resorbtion.
- a primary hyperparathyroidia.
- a combination of the previous causes.
The calcium oxalate is probably the crystal that one meets the
most frequently in a urinary sediment. In the majority of cases,
the presence of these crystals is without any clinical meaning.
According to Conyers, only 10 to 15% of the urinary oxalate is
directly related to the diet. The majority of the urinary
oxalates is produced by the metabolism (glyoxilic acid cycle). It
seems that even light hyperoxaluria is, after the decreased
urinary volume, the most significant factor in the recurrent
calcium oxalate urolithiasis.
In some cases, the crystallization of the calcium oxalate is
massive and catastrophic. A typical example of the oxalate
clinical catastrophe is the cases of ethylene glycol poisoning.
In this situation, one can find oxalate crystals in the patient's
tissues. The toxicity syndrome affects organs like the liver, the
kidney, and the brain and is accompanied by a metabolic acidosis.
Naturally, the oxalate crystalluria is massive, and is
predominated by the ovoid crystals (Whewellite) forming
Calcium oxalate casts are highly significant. These
imply that the oxalate crystals were already formed when the
urine was at it's maximum dilution.
Conyers has reported other
substances that can lead to oxalosis. Some of these substances
are use as glucose substitutes in parental alimentation.
Other causes of hyperoxaluria are:
- primary hyperoxaluria (a rare genetic disease).
- pyridoxine deficiency (vit B6 ).
- an increased intestinal absorption of oxalates.
Fatty acids are competing with oxalate for the
intestinal calcium. In fat malabsorbtion, the
increase of unabsorbed fatty acids mobilizes the
calcium leaving the oxalate, free to be absorbed. Intestinal
calcium limits the absorption of oxalate.
An increased elimination of urate is most frequently caused by
a high purine diet. Overproduction, can also be a cause of
hyperuricosuria. With a urinary pH greater than 5,5, amorphous
urates will be the major crystal form. Below 5.5, uric acid
crystals are observed.
It is not rare to observe calcium oxalate crystals with
amorphous urate in the same urinary sediment. Urate crystals seem
to have an enhancer effect on the calcium oxalate crystal
formation. A possible explanation is that urates and oxalates are
competing for the litho-inhibitor macromolecules.
The chelating effect of citrate is known to reduce the
saturation in calcium salt. Also, the soluble chelating calcium
complex seems to have an inhibiting effect on crystal formation.
One can therefore expect an increase in crystals formation, and
even urolithiasis in conditions leading to hypocitraturia.
Hypocitraturia is seen in conditions like in:
- renal tubular acidosis, especially of the distal type.
(RTA type I)
- chronic diarrhea.
- excessive animal protein intakes.
Many bacteria infecting the urinary tract reduce the citrate
5% of the hypocitraturia are of unknown causes.
Approximately 66 to 75% of the uric acid is eliminated by the
urine. The quantity to eliminate depends mostly on the diet
(meat). In increased uricosuria, values > 4,5 mmol/d are
Uric acid crystals are formed when the urinary pH is <5,5
since the pK of uric acid is 5,5.
Uric acid crystalluria is mainly due to a poor dilution volume
at an acid pH, or due to an overproduction. In the majority of
cases, this finding is of little clinical value and represents a
Some conditions, like chronic diarrhea, can be responsible for
uric acid urolithiasis. Many of these patients will also have
Uric acid stones are seen in cases of gout, myeloproliferative
syndrome, glycogenosis and neoplasms.
Cystine crystals are found in urine of almost exclusively
patients with a genetic disease giving an impairment with the
tubular reabsorption of the basic aminoacid: lysine, arginine,
ornithine and cystine. This disease is called cystinuria. For a
few patients with cystinuria, stones will develop. The
urolithiasis is highly dependent of the urinary pH and water
intake. Cystine is less soluble at a pH lower than 5,0
(saturation 300 mg/l); saturation is of 500 mg/l at a pH of 7,4.
Infection with urea splitting bacteria (ex: proteus species)
leads to a production of ammonia an alkalinization of the urine.
The produced ammonia generates magnesium ammonium phosphate
crystals, also called triple phosphates. The mineralogical name
of triple phosphate is Struvite. Triple phosphates are usually
found with amorphous phosphates, owing to their low solubility at
Solid substances are divided in two large groups, amorphous
substances and crystalline substances. Crystals have defined
geometrical shapes while amorphous substances have not. More,
crystals have a precise melting point, while amorphous substances
have a melting point that spreads over an interval of
temperature. In crystallography, one speaks of planes, axes, and
angles to describe their shape. Crystals, while preserving their
primary shape, have a very variable size, but the ratios and
angles between the faces and between the sides, are constant.
A characteristic of crystals is that
their form is predictable from the elementary structure. There
are 230 possible geometrical forms that are grouped in 32
classes, based upon the arrangement of elements of symmetry.
These elements of symmetry are axes of symmetry, planes of
symmetry, the center of symmetry. These 32 classes are further
regrouped in 6 crystalline systems. Crystallographic constants of
these crystalline systems are described by a system of
coordinate, 3 axes (a, b, c), and by the angles formed by these
axes between them (a, b, g).
a = b = c
a = b = g = 90°
a = b <> c
a = b = g = 90°
calcium oxalate 2(H2O)
« Weddellite »
a = b <> c
a = 120° b = g = 90°
a = b = c
a = b = g <> 90°
a <> b <>* c
a = b= 90° et g <> 90°
Calcium oxalate (H2O) « Whewellite »
Calcium hydrogen phosphate
Sodium acid urate
a <> b <> c
a <> b <> g <> 90°
Sodium acid urate
Crystals of the cubic system are said to be isotropic, since
these have the same properties in all direction. One of these
properties is the refractive index. Crystals of the other systems
are said to be anisotropic, having two (birefringent) or even
three refractive indexes. Anisotropic crystals subdivide into two
groups: uniaxial (two refractive indexes) and biaxial (three
refractive indexes). Crystals of the tetragonal system and the
hexagonal system are uniaxial while the orthorombic, monoclinic
and the triclinic are biaxial.
Some anisotropic crystals form interference patterns when
viewed under polarized light. Uric acid are polychromatic, and
cholesterol ester in a liquid crystal state generates a maltese
Birefringent is a crystal property
The following table shows the birefringent behavior of some
crystals found in urine.
Birefringent characteristics of
crystals found in urine
|None to light
||Calcium oxalates 2(H2O)
||Calcium oxalates (H2O)
Urine is a complex medium which influences the crystallization
process. The same substance can crystallize into different shapes
depending on the urine composition. Crystals found in urine are
often truncated and eroded. Spherical crystals are frequent.
Slow crystallization tends to give larger crystals.