|Year : 2017 | Volume
| Issue : 4 | Page : 91-95
Medical therapy for primary expulsion of urinary calculi: A review
Mushabab A Al-Ghamdi1, Abubakar Abdulkadir2
1 Department of Internal Medicine, College of Medicine, University of Bisha, Kingdom of Saudi Arabia
2 Department of Surgery, Bayero University, Kano, Nigeria
|Date of Web Publication||11-Apr-2018|
Dr. Mushabab A Al-Ghamdi
Department of Internal Medicine, College of Medicine, University of Bisha, PO Box 60, Bisha
Kingdom of Saudi Arabia
Urinary calculi are relatively common worldwide. Open surgical removal and minimally invasive surgery are effective in treating calculi but are associated with a cost and significant complications. In addition, extracorporeal shock waves lithotripsy and minimally invasive surgery are not widely available in resource-limited countries. Medical treatments for expulsion of urinary calculi provide noninvasive, relatively cheaper and safer alternatives to open surgery as well as to minimally invasive surgery for small stones. However, these modes of therapy are not widely used despite mounting evidence of their efficacy. The aim of this review is to appraise the existing literature on medical therapies for primary expulsion of urinary calculi. We searched Medline, EMBASE, CINAHL, AJOL and Cochrane database, for randomized controlled trials on urinary calculi using the search terms “urinary calculi” (MESH for Medline) AND “expulsion” OR medical treatment. We also searched reference list of relevant articles. The literature was appraised and summarized in this review. Twenty-seven randomized controlled trials on medical therapies for expulsion of urinary stones were found from various databases and hand-search of references of articles. We also retrieved some basic science, epidemiologic, and meta-analytic research related to urinary calculi. Medical expulsive therapies, especially alpha-blockers and calcium channel blockers have been shown to be effective in many trials as well as meta-analysis of clinical trials. We conclude that medical therapies for primary expulsion of small size urinary calculi should be considered in suitable patients, especially in resource-limited settings where facilities for shockwave lithotripsy (SWL) and minimally invasive surgeries are not readily available.
Keywords: Medical expulsion, urinary calculi, urinary stones, urolithiasis
|How to cite this article:|
Al-Ghamdi MA, Abdulkadir A. Medical therapy for primary expulsion of urinary calculi: A review. Sub-Saharan Afr J Med 2017;4:91-5
|How to cite this URL:|
Al-Ghamdi MA, Abdulkadir A. Medical therapy for primary expulsion of urinary calculi: A review. Sub-Saharan Afr J Med [serial online] 2017 [cited 2019 Dec 12];4:91-5. Available from: http://www.ssajm.org/text.asp?2017/4/4/91/229755
| Introduction|| |
Urinary calculi are relatively common worldwide. The incidence was reported to have increased in the last quarter of the 20th century for all genders, blacks, and whites in the United States. It affects 13 and 7% of men and women, respectively, in the USA and Europe with a recurrence rate of 50% in 5 years.
The epidemiology of urolithiasis has not been extensively studied in Nigeria, but there are reports from different parts of the country, and some parts of the country referred to as stone belts.,,
Various surgical options for the treatment of urinary calculi are available ranging from minimally invasive surgery (ureteroscopy with endoscopic lithotripsy and retrograde intrarenal surgery) to open surgical removal. Unfortunately, these treatment modalities are associated with significant complications even with minimally invasive surgery.,, The advent of extracorporeal shockwave lithotripsy (ESWL) in the 1980’s has reduced the morbidity from the treatment of urinary calculi, but it is expensive, and may not be readily available in many resource-limited countries.
Nonsurgical treatments for expulsion of urinary calculi provide noninvasive, cheaper, and safer alternatives to surgery as well as for patients, who cannot afford ESWL, or where there are no facilities for shockwave lithotripsy (SWL), especially when the need for active intervention is not urgent.
The aim of this review is to appraise the existing literature on medical therapies for the primary expulsion of urinary calculi, while highlighting the limitations of these modes of treatment.
| Materials and methods|| |
We searched Medline, EMBASE, CINAHL, Cochrane database, and AJOL for randomized controlled trials on urinary calculi using the search terms “urinary calculi” (MESH for Medline) AND “expulsion” OR medical treatment. Reference list of relevant articles were also searched. We also retrieved some basic science, epidemiologic, and meta-analytic research related to urinary calculi. The literature was appraised for information on medical treatment of urinary calculi and summarized in this review.
| Resultsand discussion|| |
Twenty-seven randomized controlled trials on various medical therapies for the expulsion of urinary calculi (also called urolithiasis urinary lithiasis, calculous disease of the urinary tract, urinary stone disease, or urinary calculous disease) were found from various databases and hand search of reference list of articles. The full texts of fifteen trials, which formed the core of this review, were retrieved, as summarized in [Table 1].
|Table 1: Summary of medical therapies for primary expulsion of urinary calculi|
Click here to view
The retrieved trials are appraised below.
The basis for the use of alpha-blockers as well as calcium channel blockers stemmed from studies in animal models, which showed that their effect on ureteral stones result in increased amplitude of ureteral smooth-muscle contraction, decreased frequency of peristaltic contractions, and decreased ureteral tone. Further evidence suggests that relaxing the ureter in the region of the stone and increasing hydrostatic pressure proximal to the stone on using adrenergic α-antagonists and calcium-channel blockers help to facilitate stone passage.,,
Several trials have been published on the use of alpha-blockers for the expulsion of urinary calculi.,,,,,,,, The most convincing evidence for the efficacy of alpha-blockers was the meta-analysis of these trials published by Hollingsworth et al. in 2006. In that meta-analysis, the results from various trials were pooled and the pooled risk ratio for alpha-blockers was 1.54, implying that the patients who had alpha-blockers were 54% more likely to pass stones than controls. Newer trials conducted further support the efficacy of alpha-blockers for medical expulsion of renal stones.
Calcium channel blockers
Several randomized controlled trial (RCTs) have looked at the efficacy of calcium channel blockers for primary expulsion of urinary calculi.,,,,,,, The results of these trials have also been pooled in the meta-analysis by Hollingsworth et al. in 2006. The risk ratio of the expulsion of stones by calcium channel blockers with steroids was 1.90 implying that patients in the treatment arm (calcium channel blockers/steroids) were 90% more likely to expel stones than controls. Additional RCTs published after that meta-analysis were also in keeping with this finding.
The main limitation of the trials on alpha-blockers and calcium channel blockers is that the primary outcome in these trials is the proportion of patients, who are stone-free, rather than time to stone-free state. Considering the fact that the spontaneous expulsion rate of calculi is reported to be around 71–98% for small (≤5 mm) distal ureteral stones,,, the effectiveness of medical therapy would be more established, if the time to stone-free state is significantly lower in the alpha blockers/calcium channel blockers than controls. However, a qualitative analysis of the time to stone free-state in the meta-analysis by Hollingsworth et al. suggests that the time to stone-free state was lower in the alpha blockers/calcium channel blockers group. This would have been more convincing if it was proved statistically by a time-to event analysis. It is also important to note that some of these trials were conducted on relatively small sized renal stones (mean stone diameter <5 mm) although mean stone size in various trials range from 3.86 mm to 35.93 mm. It has been estimated that 90% of stones <5 mm and 15% of stones between 5 and 8 mm will pass spontaneously within 4 weeks. In such scenario, medical expulsion therapy may decreases analgesic requirement by the patient. It has been estimated that 95% of stones larger than 8 mm will require urological intervention. However, some experts consider size as a determinant of stone expulsion more of a medical myth than reality. Another limitation of the use of medical expulsive therapy is the potential side effects of the medications although data from the meta-analysis by Hollingsworth et al. suggest that the most frequently used medications (alpha-blockers and calcium channel blockers) are well tolerated.
Despite these limitations, the balance of current evidence suggests that alpha-blockers/calcium channel blockers maybe effective in the primary expulsion of renal and ureteric stones with diameter up to 35 mm.
Urinary calculi tend to cause ureteral inflammatory reactions and submucosal edema in the vicinity of a stone, which may aggravate urinary obstruction and calculus retention. Corticosteroids, by decreasing inflammation and edema related to mechanical irritation, may aid in the expulsion of calculi. However, steroids have only been used in combination with calcium channel blockers and alpha blockers.,,,
Hydration and forced diuresis
Theoretically, hydration and forced diuresis should increase urine flow and aid in the expulsion of urinary calculi. However, current evidence has not proven the efficacy of this traditional therapy for urolithiasis. In a vigorous systematic review by Worster and Richards in 2005, only one randomized control trial was found, which showed that hydration was not effective in the expulsion of urinary calculi. In another randomized controlled trial by Springhart et al. in 2006, no benefit of forced diuresis was found compared to minimal hydration.
Terpenes are noted to have spasmolytic, analgesic, anti-inflammatory, and diuretic properties. Rowatinex, which is a combination of terpenes, according to Romics et al., when used for medical expulsion therapy, showed fast and efficient stone expulsion. Aldermir on the other hand reported that Rowatinex had no significant effect on the clearance rate of distal ureteric calculi that were <10 mm unlike Tamsulosin.
Inversion therapy has mainly been studied as an adjunct therapy for stone fragment expulsion after SWL.,, Only one RCT was found on the use of inversion therapy for primary expulsion of urinary calculi. Further RCTs are needed to establish the efficacy and safety of this mode of therapy for primary expulsion of urinary calculi.
Duration of medical expulsion therapy
No randomized control trial is currently available on the appropriate duration for the medical expulsion therapy. Individual experience and opinion from experts, however, suggest approximately 4–6 weeks in the absence of contraindications such as persistent pain, urosepsis, deterioration in renal functional reserve, or worsening hydroureteronephrosis.
Current use of medical expulsion therapy
Medical expulsive therapy is not widely used despite growing evidence from clinical trials in the support of its efficacy., Hollingsworth et al. postulated two reasons for that: first, minimally invasive surgical techniques, such as SWL and ureteroscopy, have evolved to allow for the resolution of stone burden. Secondly, the reports of empirical data for medical therapies have appeared mainly in urological publications, and therefore, the availability of such therapies might not be well-known to physicians from other disciplines, who are often the initial contact for patients with urolithiasis. It is hoped that this review will sensitize clinicians in our environment on the use of medical expulsive therapy for urolithiasis in a patient, in whom active intervention is not indicated.
| Conclusion|| |
Medical therapies for primary expulsion of renal and ureteric stones, especially the use of alpha-blockers and calcium channel blockers have been shown to be effective in many randomized controlled trials. These therapies should be considered in suitable well-counseled patients when pain control is adequate, the functional renal reserve is good, and there is no evidence of urosepsis especially in resource-limited settings where facilities for minimally invasive surgery and SWL are not readily available.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time trends in reported prevalence of kidney stones in the United States: 1976–1994. Kidney Int 2003;63:1817-23.
Mshelia DS, Gali BM, Naaya UH, Habu SA. Chemical composition of urinary calculi in Maiduguri, Nigeria. Afr J Med Med Sci 2005;34:185-8.
Olapade-Olaopa EO, Agunloye A, Ogunlana DI, Owoaje ET, Marinho T. Chronic dehydration and symptomatic upper urinary tract stones in young adults in Ibadan, Nigeria. West Afr J Med 2004;23:146-50.
Ekwere PD. Urinary calculous disease in south-eastern Nigeria. Afr J Med Med Sci 1995;24:289-95.
Kramolowsky EV. Ureteral perforation during ureterorenoscopy: Treatment and management. J Urol 1987;138:36-8.
Harmon WJ, Sershon PD, Blute ML, Patterson DE, Segura JW. Ureteroscopy: Current practice and long-term complications. J Urol 1997;157:28-32.
Schuster TG, Hollenbeck BK, Faerber GJ, Wolf JS. Complications of ureteroscopy: Analysis of predictive factors. J Urol 2001;166:538-40.
Bierkens AF, Hendrikx AJ, De La Rosette JJ, Stultiens GN, Beerlage HP, Arends AJ et al.
Treatment of mid- and lower ureteric calculi: Extracorporeal shock-wave lithotripsy vs laser ureteroscopy. A comparison of costs, morbidity and effectiveness. Br J Urol 1998;81:31-5.
Lotan Y, Gettman MT, Roehrborn CG, Cadeddu JA, Pearle MS. Management of ureteral calculi: A cost comparison and making analysis. J Urol 2002;167:1621-9.
Cervenakov I, Fillo J, Mardiak J, Kopecny M, Smirala J, Lepies P. Speedy elimination of ureterolithiasis in lower part of ureters with the alpha 1-blocker—Tamsulosin. Int Urol Nephrol 2002;34:25-9.
Dellabella M, Milanese G, Muzzonigro G. Efficacy of Tamsulosin in the medical management of juxta vesical ureteral stones. J Urol 2003;170:2202-5.
Dellabella M, Milanese G, Muzzonigro G. Randomized trial of the efficacy of Tamsulosin, Nifedipine and Phloroglucinol in medical expulsive therapy for distal ureteral calculi. J Urol 2005;174:167-72.
Porpiglia F, Ghignone G, Fiori C, Fontana D, Scarpa RM. Nifedipine versus Tamsulosin for the management of lower ureteral stones. J Urol 2004;172:568-71.
Resim S, Ekerbicer H, Ciftci A. Effect of Tamsulosin on the number and intensity of ureteral colic in patients with lower ureteral calculus. Int J Urol 2005;12:615-20.
Küpeli B, Irkilata L, Gürocak S, Tunç L, Kiraç M, Karaoğlan U et al.
Does Tamsulosin enhance lower ureteral stone clearance with or without shock wave lithotripsy? Urology 2004;64:1111-5.
Yilmaz E, Batislam E, Basar MM, Tuglu D, Ferhat M, Basar H. The comparison and efficacy of 3 different alpha1-adrenergic blockers for distal ureteral stones. J Urol 2005;173:2010-2.
Taghavi R, Darabi MR, Tavakoli K, Keshvari M. Survey of the effect of Tamsulosin and Nifedipine on facilitating juxtavesical ureteral stone passage. J Endourol 2005;19(Suppl 1):A9.
Tekin A, Alkan E, Beysel M, Yucebas E, Asian R, Sengor F. Alpha-1 receptor blocking therapy for lower ureteral stones: A randomized prospective trial. J Urol 2004;17(Suppl 4):304.
Singh SK, Pawar DS, Griwan MS, Indora JM, Sharma S. Role of Tamsulosin in clearance of upper ureteral calculi after extracorporeal shock wave lithotripsy: A randomized controlled trial. Urol J 2011;8:14-20.
Borghi L, Meschi T, Amato F, Novarini A, Giannini A, Quarantelli C et al.
Nifedipine and methylprednisolone in facilitating ureteral stone passage: A randomized, double-blind, placebo-controlled study. J Urol 1994;152:1095-8.
Staerman F, Bryckaert PE, Colin J, Youinou Y, Brandt B, Lardennois B. Nifedipine in the medical treatment of symptomatic distal ureteral calculi. Eur Urol 2005;37:28.
Cooper JT, Stack GM, Cooper TP. Intensive medical management of ureteral calculi. Urology 2000;56:575-8.
Porpiglia F, Destefanis P, Fiori C, Fontana D. Effectiveness of Nifedipine and Deflazacort in the management of distal ureter stones. Urology 2000;56:579-82.
Skrekas T, Liapis D, Kalantzis A, Argyropoulos A, Doumas K, Lycourinas M. Increasing the success rate of medical therapy for expulsion of distal ureteral stones using adjunctive treatment with calcium channel blocker. Eur Urol Suppl 2003;2:82.
Worster A, Richards C. Fluids and diuretics for acute ureteric colic. Cochrane Database Syst Rev 2005;CD004926.
Springhart WP, Marguet CG, Sur RL, Norris RD, Delvecchio FC, Young MD et al.
Forced versus minimal intravenous hydration in the management of acute renal colic: A randomized trial. J Endourol 2006;20:713-6.
Romics I, Siller G, Kohnen R, Mavrogenis S, Varga J, Holman E. A special terpene combination (Rowatinex®
) improves stone clearance after ESWL in urolithiasis: Results of a placebo controlled randomised control trial. Urol Int 2011;86:102-9.
Aldermir M, Ucquive VE, Kayigil O. Evaluation of the efficacy of Tamsulosin and Rowatinex in patients with distal ureteral stone: Prospective randomised controlled study. Int Urol Nephrol 2011;43:76-83.
Yu X, Chen ZQ, Yang WM, Liu JH, Zhou XC, Wang SG et al.
[Application of inversion-table in the treatment of lower pole renal stones]. Zhonghua Wai Ke Za Zhi 2009;47:255-7.
Laird JM, Roza C, Cervero F. Effects of artificial calculosis on rat ureter motility: Peripheral contribution to the pain of ureteric colic. Am J Physiol 1997;272:R1409-16.
Sivula A, Lehtonen T. Spontaneous passage of artificial concretions applied in the rabbit ureter. Scand J Urol Nephrol 1967;1:259-63.
Maggi CA, Giuliani S. A pharmacological analysis of calcium channels involved in phasic and tonic responses of the guinea-pig ureter to high potassium. J Auton Pharmacol 1995;15:55-64.
Morita T, Wada I, Suzuki T, Tsuchida S. Characterization of alpha-adrenoceptor subtypes involved in regulation of ureteral fluid transport. Tohoku J Exp Med 1987;152:111-8.
Hollingsworth JM, Rogers MA, Kaufman SR, Bradford TJ, Saint S, Wei JT et al.
Medical therapy to facilitate urinary stone passage: A meta-analysis. Lancet 2006;368:1171-9.
Hubner WA, Irby P, Stoller ML. Natural history and current concepts for the treatment of small ureteral calculi. Eur Urol 1993;24:172-6.
Miller OF, Kane CJ. Time to stone passage for observed ureteral calculi: A guide for patient education. J Urol 1999;162:688-90.
Ueno A, Kawamura T, Ogawa A, Takayasu H. Relation of spontaneous passage of ureteral calculi to size. Urology 1977;10:544-6.
Higgins JP, Green S, editors. Analyzing and Presenting Results. Cochrane Handbook for Systematic Reviews of Interventions 4. 2. 6 [updated September 2006]; Section 8. In: The Cochrane Library, Issue 4. Chichester, UK: John Wiley BT & Sons, Ltd. 2006.
Marx J, Hockberger R, Walls R. Rosen’s Emergency Medicine Concepts and Clinical Practices. Philadelphia: Mosby Inc; 2006.
Liu MB, Henderson SO. Myth: Nephrolithiasis and medical expulsive therapy. Can J Emerg Med 2007;9:463-5.
Yamaguchi K, Minei S, Yamazaki T, Kaya H, Okada K. Characterization of ureteral lesions associated with impacted stones. Int J Urol 1999;6:281-5.
Saita A, Bonaccorsi A, Marchese F, Condorelli SV, Motta M. Our experience with Nifedipine and prednisolone as expulsive therapy for ureteral stones. Urol Int 2004;72(Suppl 1):43-5.
Micali S, Grande M, Sighinolfi MC, De Stefani S, Bianchi G. Efficacy of expulsive therapy using Nifedipine or Tamsulosin, both associated with ketoprofene, after shock wave lithotripsy of ureteral stones. Urol Res 2007;35:133-7.
Zhu Y, Duijvesz D, Rovers MM, Lock TM. Alpha-blockers to assist stone clearance after extracorporeal shock wave lithotripsy: A meta-analysis. BJU Int 2010;106:256-61.
Alhassan SU, Adamu B. Adjunctive Medical Expulsive Therapy for Kidney and Ureteral Stone Fragments Following Shock Wave Lithotripsy (Protocol). The Cochrane Library, Issue 6. The Cochrane Collaboration. John Wiley & Sons, Ltd.: 2011.
Stroup SP, Garvin AN, Irby J, Stroup KK, L’Esperance JO, Auge BK. Practice patterns of primary care providers and urologists for use of medical expulsion therapy. Mil Med 2010;175:883-9.
Hollingsworth JM, Davis MM, West BT, Wolf JS Jr, Hollenbeck BK. Trends in medical expulsive therapy use for urinary stone disease in U. S. emergency departments. Urology 2009;74:1206-9.