Objective: The aim of this study was to determine the feasibility of using snake venom thrombin-like enzyme (SVTLE) and/or ethylenediaminetetraacetic acid (EDTA) to dissolve calcium oxalate stones in vitro. Methods: Seven calcium oxalate stones were incubated with various chemolytic agents [EDTA, Tris-HCl/EDTA (TE) buffer or SVTLE diluted in TE buffer]. The pH, calcium concentration, stone weight and stone surface integrity were recorded, as well as related pathological changes to bladder mucosae. Results: Compared to all other solutions, those containing SVTLE and buffered EDTA had higher concentrations of mobilized calcium and caused significantly more stone weight loss, stone fragility and gaps in the calcium crystals. Also, there were no adverse pathological effects on rabbit bladder mucosae from any of the solutions. Conclusions: The data indicate that buffered EDTA and SVTLE can be used to dissolve calcium oxalate stones and, at the concentrations used here, do not damage tissue.

Keywords:
In vitro dissolution, Calcium oxalate stones, Ethylenediaminetetraacetic acid, Snake venom thrombin-like enzyme
1.
Miano R, Germani S, Vespasianin C: Stones and urinary tract infections. Urol Int 2007;79(suppl 1):32-36.
2.
Heimbach D, Kourambas J, Zhong P, et al: The use of chemical treatments for improved comminution of artificial stones. J Urol 2004;171:1797-1801.
3.
Verplaetse H, Verbeeck RM, Verbaeys A, et aI: Solubility of calcium oxalate monohydrate and hydroxyapatite in EDTA solutions. J Urol 1986;135:608-611.
4.
Boyce W, Garvey FK: The amount and nature of the organic matrix in urinary calculi: a review. J Urol 1956;76:213-227.
5.
Durrbaum D, Rodgers AL, Amlesh S, et al: A study of crystal matrix extract and urinary prothrombin fragment 1 from a stone-prone and stone-free population. Urol Res 2001;29:83-88.
6.
Lin Y, Mao Q, Zheng X, et al: Vitamin D receptor genetic polymorphisms and the risk of urolithiasis: a meta-analysis. Urol Int 2011; 86:249-255.
7.
Ziolkowski F, Perrin DD: Dissolution of urinary stones by calculi-chelating agents. Invest Urol 1977;15:208-211.
8.
Strohmaier WL, Seilnacht J, Schubert G: Urinary stone formers with hypocitraturia and ‘normal' urinary pH are at high risk for recurrence. Urol Int 2012;88:294-297.
9.
Sheldon CA, Smith AD: Chemolysis of calculi. Urol Clin North Am 1982;9:121-130.
10.
Rigatti P, Francesca F, Ronchi F, et al: Cystine lithiasis: combined extracorporeal and litholytic treatment. Contrib Nephrol 1987;58:274-277.
11.
Stegmayr B, Anneroth G, Bergman B, et al: Urinary tract calculi dissolved by means of renacidin. An experimental study. Scand J Urol Nephrol 1990;24:215-218.
12.
Romics I, Siller G, Kohnen R, et al: A special terpene combination (Rowatinex®) improves stone clearance after extracorporeal shockwave lithotripsy in urolithiasis patients: results of a placebo-controlled randomised controlled trial. Urol Int 2011;86:102-109.
13.
Ryall RL: Glycosaminoglycans, proteins, and stone formation: adult themes and child's play. Pediatr Nephrol 1996;10:656-666.
14.
Doerfler HD, Krueger H: Interaction of Na+, K+, Li+ and Ca2+ ions in Tris-HCl buffer substrate with monolayers of phosphatidic acid and homologous phosphatidic acid alkyl esters. Colloid Polym Sci 1991;269:1157-1170.
15.
Oosterlinck W: Is there currently a future for chemolysis of calcium-oxalate urolithiasis? Eur Urol 1993;3:6-10.
16.
Grover PK, Thurgood LA, Wang T, et al: The effects of intracrystalline and surface-bound proteins on the attachment of calcium oxalate monohydrate crystals to renal cells in undiluted human urine. BJU Int 2010;105:708-715.
17.
Tu AT: Overview of snake venom chemistry. Adv Exp Med Biol 1996;391:37-62.
18.
Jiang W, Ma T, Su X, et al: Enzymatic activities and functional characterization of a novel recombinant snake venom proteinase from Agkistrodon acutus. Biochimie 2009;91:277-287.
19.
Costa FL, Rodrigues RS, Izidoro LF, et al: Biochemical and functional properties of a thrombin-like enzyme isolated from Bothrops pauloensis snake venom. Toxicon 2009;54:725-735.
20.
Sheir KZ, Mansour O, Madbouly K, et al: Determination of the chemical composition of urinary calculi by noncontrast spiral computerized tomography. Urol Res 2005;33:99-104.
21.
Manglaviti G, Tresoldi S, Guerrer CS, et al: In vivo evaluation of the chemical composition of urinary stones using dual-energy CT. AJR Am J Roentgenol 2011;197:W76-W83.
22.
Huri E, Tatar I, Germiyanoglu C, et al: Evaluation of urinary stones ex vivo with micro-computed tomography: preliminary results of an investigational technique. Urol J 2011;8:185-190.
23.
Zarse CA, Hameed TA, Jackson ME, et al: CT visible internal stone structure, but not Hounsfield unit value, of calcium oxalate monohydrate (COM) calculi predicts lithotripsy fragility in vitro. Urol Res 2007;35:201-206.
© 2013 S. Karger AG, Basel
2013
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.