INVESTIGATIVE UROLOGY

Effect of Extract of Phyllanthus Niruri on Crystal Deposition in Experimental Urolithiasis
Barros ME, Lima R, Mercuri LP, Matos JR, Schor N, Boim MA
Department of Medicine, Renal Division, Federal University of Sao Paulo, Sao Paulo, SP, Brazil
Urol Res. 2006; 34: 351-7

• Phyllanthus niruri (Pn) is a plant that has been shown to interfere in the growth and aggregation of calcium oxalate (CaOx) crystals. In the present study we evaluated the effect of Pn on the preformed calculus induced by introduction of a CaOx seed into the bladder of male Wistar rats. Pn treatment (5 mg/rat/day) was initiated immediately or 30 days after CaOx seeding and thus in the presence of a preformed calculus. Animals were sacrificed 50 or 70 days after surgery. The resulting calculi were weighed and analyzed by X-ray diffraction, stereomicroscopy and scanning electronic microscopy. Precocious Pn treatment reduced the number (75%, P < 0.05) and the weight (65%, P < 0.05) of calculi that frequently exhibited a matrix-like material on its surface, compared to the untreated CaOx group. In contrast, Pn treatment in the presence of a preformed calculus did not prevent further calculus growth; rather, it caused an impressive modification in its appearance and texture. Calculi from Pn-treated animals had a smoother, homogeneous surface compared to the spicule shape of calculi found in the untreated CaOx group. XRD analysis revealed the precipitation of struvite crystals over the CaOx seed and Pn did not change the crystalline composition of the calculi. This suggests that Pn interfered with the arrangement of the precipitating crystals, probably by modifying the crystal-crystal and/or crystal-matrix interactions. Results suggest that Pn may have a therapeutic potential, since it was able to modify the shape and texture of calculi to a smoother and probably more fragile form, which could contribute to elimination and/or dissolution of calculi.
  
  
• Editorial Comment
  Phyllanthus niruri, is a plant used in Brazilian folk medicine. Its infusion tea is called “break-stone tea” and is widely used in Brazil for treatment of urolithiasis. The authors of this paper have been studying the effects of Phyllanthus niruri on urolithiasis at least for the last 10 years and have contributed a lot for the specialized literature (1-3).
  In the present experimental study, the authors used a model of preformed calculus induced by introduction of a CaOx seed into the bladder of male Wistar rats. The authors elegantly demonstrated, by using X-ray diffraction, stereomicroscopy and scanning electronic microscopy, that precocious treatment with Phyllanthus niruri significantly reduced the number and the weight of calculi compared to the untreated CaOx seeding group. Also, on scanning electronic microscopy, in treated group, it was observed a homogeneous surface compared to the spicule shape of calculi found in the untreated CaOx group. These findings, together with previous findings from the same research group (1-3), suggest objectively that Phyllanthus niruri (“break-stone tea”) might have therapeutic potential for urolithiasis.
  Interesting, in a recent published work from Italy, it was assessed the efficacy of Phyllanthus niruri after extracorporeal shock wave lithotripsy (ESWL) for renal stones (4). The authors evaluated prospectively 150 patients with renal stones that were as large as 25 mm and composed of calcium oxalate. All patients received 1 to 3 ESWL with Dornier Lithotriptor S. After treatment, 78 of 150 patients (52%) underwent therapy with Phyllanthus extract for at least 3 months (group 1). The other 72 of 150 patients (48%) were used as a control group (group 2). No significant difference in stone size between the 2 groups was found. Stone clearance was assessed after 30, 60, 90 and 180 days by abdominal X-ray and ultrasonography. Although no significant difference was found at the end point of the follow-up (180 days), for lower caliceal stones (56 patients) the stone-free rate was 93.7% in the treatment group and 70.8% in the control group (p = 0.01). The authors concluded that regular self-administration of Phyllanthus niruri after ESWL for renal stones results in an increased stone-free rate that appears statistically significant for lower caliceal location. Since ESWL for lower pole stones is challenging and present poor results when compared to other locations stones (5), the efficacy and the lack of side effects make Phyllanthus niruri therapy suitable to improve overall outcomes after extracorporeal shock wave lithotripsy for lower pole stones.

References
1. Barros ME, Schor N, Boim MA: Effects of an aqueous extract from Phyllanthus niruri on calcium oxalate crystallization in vitro. Urol Res. 2003; 30: 374-9.
2. Freitas AM, Schor N, Boim MA: The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation. BJU Int. 2002; 89: 829-34.
3. Campos AH, Schor N: Phyllanthus niruri inhibits calcium oxalate endocytosis by renal tubular cells: its role in urolithiasis. Nephron. 1999; 81: 393-7.
4. Micali S, Sighinolfi MC, Celia A, De Stefani S, Grande M, Cicero AF, et al.: Can Phyllanthus niruri affect the efficacy of extracorporeal shock wave lithotripsy for renal stones? A randomized, prospective, long-term study. J Urol. 2006; 176: 1020-2.
5. Sampaio FJ: Renal collecting system anatomy: its possible role in the effectiveness of renal stone treatment. Curr Opin Urol. 2001; 11: 359-66.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil