30
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
solutions are transformed into
undersaturated systems. The effect of
the presence of [Ca
2+
] in the course
of the straight lines 2 and 3 in Figure
1, as compared to the non-Ca
2+
case
(line 1 in the same figure) is to be
noted. A sharp decrease in the slope
of lines 2 and 3 is observed, too.
Since the 2 solutions have the same
Ca
2+
concentration, curves 2 and 3
are parallel, as expected from the
formalism.
Discussion
The majority of urinary calculi found
in patients with urolithiasis are
predominantly of CaOX composition.
CaOX are the 2 urine substances
responsible for CaOX crystallization.
The results of our study indicate that
CaOX SF patients are different from
normal patients in regard to urinary
oxalate excretion; about 39% of SFs
excrete more oxalate than controls (
P
< .05) (see Table 1). Only 10% of them
have hypercalciuria. Few of them
(4%), however, show hypercalciuria
and hyperoxaluria together.
It seems natural to expect that
the reduction of the total amount
of oxalate that is present in the
urine of SFs could give the key to
prevention or to successful treatment
of CaOX urolithiasis. It is known,
that approximately 60% of urinary
oxalate stones are derived from the
endogenous metabolism of glycine,
glycolate, and hydroxyproline, and
25% to 30% are the end product of
dietary ascorbate metabolism. The
remaining 10% to 15% come from
dietary oxalate intake. However, there
is no means of decreasing endogenous
oxalate production. Nevertheless, one
may assume that decreasing exogenous
oxalate intake may lessen urinary
oxalate levels.
Detailed analysis performed in our
previous study indicates that HA is
comparable, in its solubility effect,
to the best known classical complex
binders of Ca
2+
or C
2
O
4
2-
ions in urine,
that is, Mg
2+
and citrate anions. This
can be seen from Table 3, in which the
stability constant
K
H
of HA calculated
according to our results (Figure 1)
is compared to
K
i
-values of [Mg
2+
],
Na-EDTA, and other known complex
formers of CaOX. We have found
that the mechanism of dissolution
of CaOX calculi follows the Nernst
model of a diffusion limited process.
At the same time, there is also a very
a significant difference in the urinary
HA concentration (
P
< .001) between
both groups (see Table 1). Thus, it
turns out that patients with oxalate
stones generally excrete less HA than
normal patients do. These results are
meaningful from a physiological point
of view considering the well-known
fact that urinary HA excretion could
be increased by oral administration
of benzoic acid (BA) derivatives
or salicylates. Moreover, the renal
excretion of HA is not limited by the
capacity of the renal tubular transport
system, even at the highest excretion
level obtained after administration of
benzoates.
Sufficient data is available, confirming
that the presence of HA in urine is
a biological marker for the presence
of organic aromatic compounds,
for example, for benzoic or toluene
exposure. Part of the toluene absorbed
is eliminated by the exhaled breath,
but a large percentage is oxidized in
the organism to BA, conjugated with
glycine, and excreted as HA in urine
according to the chemical reaction
given below
C
6
H
5
COOH + H
2
NCH
2
COOH =
Benzoic acid Glycine
C
6
H
5
CONHCH
2
COOH + H
2
O
Hippuric acid
(4)
Therefore, a high level of urinary
HA may be achieved by the intake
of BA. As a food preservative, BA
(or sodium benzoate) is added to
pickles, soft drinks, soya sauce, syrup,
and caviar. Besides, BA is naturally
present in many fruits and vegetables,
especially cranberries, prunes, and
in coffee beans. Sodium benzoate is
also the constituent of several classical
medicines (eg, cough syrups). The
origin of the increased presence of HA
in human urine is presumably in many
cases due to the BA present in the
fruits mentioned above and also from
the addition of benzoate preservatives
to food. Along with this exogenous
HA, an endogenous excretion should
be considered too. It is known
that HA may be bacteriostatic for
Escherichia coli in concentration of
1 to 2 mg/mL. Last but not least, any
of the paths mentioned above might
exert an influence on the metabolic
pathway of oxalic acid in the human
organism (Figure 2). As benzoates
bind glycine in the liver, it is expected
that the glycine-glyoxylate-oxalate
link can be influenced by moving the
equilibrium to a decreased level of the
endogenous oxalate.
It is reasonable to assume that drug
biotransformation interaction in the
human organism, connected to the
simultaneous conjugation of BA with
glycine, could be a promising way for
the development of future therapy
methods for patients with CaOX
calculi.
In assessing the efficiency of HA as
an eventual clinical solvent of CaOX
calculi, one should also bear in mind
that in the renal tract some conditions
prevail, (continuous flushing of the
calculus with fresh urine) under which
the time necessary for the dissolution
effect will be much shorter, as it is
determined by the initial value of the
dissolution rate. This possibility we
Atanassova SS, et al.
Regulation of Supersaturation in Calcium Oxalate Lithiasis
