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Clinical insight
P R O B E
• V o l . L I I I • N o . 3 • A p r – J u n 2 0 1 4
of phase transformation) and the
problem of finding out the possible
natural or pharmaceutical regulators
of this driving force, in the process of
investigating the kinetics of crystal
nucleation and growth, as well as in
the investigation of the kinetics of the
dissolution of already existing stones,
appears to be of utmost significance.
Although the relative effect of a
number of constituents of human
urine on the solubility of CaOX
has been determined in simple salt
solutions, the exact combination of
the factors that are responsible for
variations in CaOX solubility in urine
is very, yet insufficiently known.
Bearing this in mind, changes in the
urinary oxalate ion concentration
are more likely to decrease the
supersaturation of urine than
similar changes in the urine calcium
concentration. Moreover, we know
that the amount of oxalate excreted
in urine depends on endogenous
production, intestinal absorption,
dietary intake, and renal transport.
The endogenous production of
oxalate, predominantly derived from
the metabolism of glyoxylate and
ascorbates, contributes significantly
to the amount of oxalate that is
excreted in urine. We also know
that it is possible to influence oxalate
endogenous production by drug
administration. In this connection,
a number of clinical studies have
demonstrated that the intake of
certain drugs, which are essentially
benzoate derivatives, leads to an
increase in CaOX solubility. The
main route of biotransformation of
benzoic acid in human individuals
is conjugation with glycine, which
results in the formation of hippuric
acid (HA).
In previous researches, we have
found out that one of the normal
physiological constituents
of human urine—HA
(C
6
H
5
CONHCH
2
COOH) is, in
fact, a complex forming physiological
solvent of calcium oxalate. Our in
vitro experiments showed that in
the presence of HA, the solubility of
CaOX increases considerably and that
in physiological solutions, in which
HA is in concentrations approximately
5 to 6 times over its normal
physiological concentration in urine
(5 to 14 mmol/24 h), the
supersaturation in the system
decreases significantly. These
results are most meaningful from
a physiological point of view,
considering the well known fact that
the increase of the concentration of
HA in urine can be provoked by the
per os administration of benzoic acid
derivatives. This circumstance is, in
fact, used in Quick’s well known test
of liver function. This test reflects
on the metabolism of aromatic
complexes in the human organism
and it is a demonstration of the long
ago established fact that HA is the
end product of the detoxification
of aromatic complexes in human
individuals. It has been proven in
recent years that the supersaturation
in urine is determined not so much by
the concentration of ions, constituting
the concrements, but rather more by
the presence or absence of complex
forming ions in urine. This has been
evident since Hammarsten’s classic
studies, according to which many
ions, such as Mg
2+
, or citrate ions,
which are also normally present in
urine, increase the solubility of CaOX
in aqueous solutions by forming
complexes with either the Ca
2+
or the
C
2
O
4
2−
ions. Thus, Mg
2+
and citric
ions are to be considered as the 2
regulators of supersaturation in urine,
concerning CaOX precipitation.
However, the oral administration of
these 2 complexing agents does not
lead to encouraging clinical results, as
they undergo metabolization in the
human organism. From our already
quoted investigations, it follows
that the concentration of HA also
determines, essentially, the solubility
of CaOX and that this substance may
be the third and even most significant
biological regulator of CaOX
supersaturation in human urine.
Until now, no biological or
biochemical analysis has been
performed concerning the possible
correlation between HA concentration
in urine and the inclination to
CaOX calculosis. The experimental
investigations mentioned earlier and
obtained in our in vitro experiments
on the dissolution of CaOX in
physiological solutions, containing
an increased concentration of HA,
necessitated such a generalized
physiological analysis and the results
of which are presented here.
Patients andMethods
Two types of experiments were
performed in the framework of our
investigation.
(1) Clinical laboratory analysis on the
concentration of HA in urine and the
amount of total urine excretion of HA
in patients with CaOX stones, as well
as, in a healthy control group
(2) An investigation on the kinetics
of the dissolution of CaOX calculi in
physiological solutions, containing
various concentrations of HA
Patients studied
Stone formers
Fifty-six patients (30 men and 26
women), whose age ranged from 14
to 65 years, at the beginning of the
disease, and who had had their CaOX
renal calculi removed (spontaneously,
by surgery or through extracorporeal
lithotripsy [ESWL]). Each patient had
a known clinical history of his disease,
including data for episodes of a renal
Atanassova SS, et al.
Regulation of Supersaturation in Calcium Oxalate Lithiasis
