A new litholytic therapy for nephrolithiasis

Pn is a plant belonging to the Euphorbiaceae family, which is so widely distributed, both in many tropical and subtropical countries, and it is generally used in Brazilian folk medicine for the treatment of urolithiasis [8]. Moreover Pn shows antispasmodic and relaxants effects on many contractile tissue. These effects might also occur in urethral smooth muscle and might contribute to the elimination of smaller calculi [9].


Introduction
Urolithiasis is a widespread disease and represents the most frequent cause of hospitalisation within the urological fi eld in western countries [1,2]. The prevalence of nephrolithiasis varies between 5 and 10% and the yearly incidence is about 0,1-6% in the world population [3].
Over the last 20 years the management of this disease has changed radically. The medical therapy has experienced an evolving role in urolithiasis treatment by correcting lithogenous processes and active expulsion of the stone [4][5][6].
Nowadays, among new litholytic drugs, there is a phytotherapeutical agent such as the aqueous extract of Phyllantus niruri (Pn) [7].
Pn is a plant belonging to the Euphorbiaceae family, which is so widely distributed, both in many tropical and subtropical countries, and it is generally used in Brazilian folk medicine for the treatment of urolithiasis [8]. Moreover Pn shows antispasmodic and relaxants effects on many contractile tissue.
These effects might also occur in urethral smooth muscle and might contribute to the elimination of smaller calculi [9].
The aim of the study was to evaluate the effi cacy of Pn in young patients affected by renal stones of size < 10 mm.

Results
We observed, in treated group, n.13 patients (65%) became stone-free while in the control group only n.4 patients (20%) became stone free (p<0.001). In treated group n. 10 patients were hypercalciuric and n. 3 patients had normal calciuria. A stone-free condition was defi ned as the absence of any stone or residual fragments less than 3 mm. Among examined patients there have not been dropouts. None of the patients suffered by strong colic pain during Pn therapy, while 5 patients within the control group reported colic pain during the 3-months-period.
After Pn therapy the hypercalciuric patients showed a signifi cant reduction in the mean urinary calcium (6.2±0.9 vs 3.8±0.9 mg/Kg/day, p<0.005) ( Table 2). In the control group n.5 hypercalciuric patients (25%) have not presented the same result (6,0±1,1 vs 5,74±0,8 mg/Kg/day, p 0.69). Moreover, in the treated group there were no signifi cant differences in the others mean values of urinary and blood parameters before and after Pn intake (Table 3).

Discussion
The formation of kidney stones is a relatively complex process [10][11][12]. Generally, urine contains a certain amount of chemical agents that take part to crystal formation or precipitation. The balance among inhibitors and promoters prevents the formation of kidney stones [10][11][12][13]. A crystal forms when molecules able to create a crystal system such as calcium-oxalate, calcium-phosphate, uric acid, and cystine reach a concentration allowing them to aggregate (calculus nucleation) [10][11][12][13][14][15]. Moreover urine contains agents such as glycosaminoglycans, uroporfi rine, nephrocalcine, magnesium and citrates that are able to inhibit over-saturation and crystallisation [16,17]. Therefore, the over-saturation of solutes, the reduced excretion of citrates, the decrease in urinary volume, pH changes and urinary anomalies all are potential factors in lithogenesis. Litholytic therapy represents an highly effective treatment for the urolithiasis' promoting factors [3,18]. New therapeutic aids include the use of phytotherapy agents such as Pn [7,19].
In our study we report the results of a Pn therapy in 20 patients suffering from nephrolithiasis. Compared to the control group, these patients have shown a higher complete lithiasis clearance (stone-free) percentage.
Several authors have investigated the Pn mechanism of action. Some authors described the Pn powerful inhibitory effect on CaOX crystal adhesion and suggested that Pn intake may reduce urinary calcium in patients with hypercalciuria [19,20].
On the other hands, Freitas et al suggested that this effect was related to a higher incorporation of glycosaminoglycans into the stone, independently from urinary excretion of citrate and magnesium. In fact the calculi from Pn treated group    Although the evidence is encouraging, the mechanism action of Pn is not totally understood. According to our experience, the drug can be a non-toxic, low-cost and effective alternative to treatment and/or prevention of urolithiasis.
Further studies are likely to provide additional confi rmation of Pn effi cacy in medical therapy for stone disease.