Medical Management of Ureteral Stones and Post Clearance Extracorporeal Shock Wave Lithotripsy (ESWL)

The lifetime risk of ureteral stone disease (urolithiasis) is estimated to be 5 – 12% in Europe and US, afflicting 13% of men and 7% of women1-3. Since 50% of patients will have a recurrence of renal colic within 5 years from their first episode, urolithiasis is chronic disease with substantial economic consequences and great public health importance4. Although patients with urolithiasis might be asymptomatic, many have pain and commonly present to emergency or outpatient departments. Provided that these patients do not need renal pelvic decompression, ie, they do not have a solitary kidney – and that pain relief can be obtained, a trial of conservative non-surgical treatment is warranted, since many of these stones pass spontaneously.

Studies have shown that spontaneous passage rates of 71-98% of small (<5 mm) ureteral stones5,6 with ureteral stone size and location as the two most important predictors of stone passage. The use of α1-adrenoceptor antagonists for medical expulsive therapy (MET) has been proposed to enhance stone passage6. Interest in these drug classes stems from the theory of ureteral-smooth muscle physiology and ureteral obstruction7.

Medical management to promote spontaneous expulsion of ureteral stones may potentially diminish healthcare expenditures.

α1-Adrenoceptor antagonists like Tamsulosin are particularly a promising class of stone expulsive agents. The proposed mechanism is the inhibition of ureteral smooth muscle contraction, with the subsequent reduction of friction force between the stone and the ureteral smooth muscle8. There are physiological data to support this hypothesis. α1-Adrenoceptor subtypes are abundantly expressed in the human ureteral smooth muscle7, and α1-adrenoceptor antagonists inhibit the α1-adrenoceptor agonist phenylephrine-induced contractions in human isolated ureters9. Recent randomized controlled trials suggest that α1-adrenoceptor antagonists would increase the frequency of spontaneous ureteral stone expulsion10.

One meta-analysis indicates that 16 studies using an α1-adrenoceptor antagonists (1235 patients, 13 of the 16 studies use of Tamsulosin) and 9 studies using a calcium channel blocker suggested that the addition of these agents compared to standard therapy 59% improved spontaneous stone expulsion (α1-adrenoceptor antagonist risk ratios (RR) 1.59, number needed to treat (NNT) 3.3; calcium channel blocker RR1.50, NNT 3.9) in patients with distal ureteral stones 11. In another Meta-analysis, 11 trials demonstrated significantly increased rates of stone expulsion with α1-adrenoceptor antagonist therapy (991 patients, 10 of the 11 studies use of Tamsulosin). Compared to patients receiving conservative therapy only, patients receiving conservative therapy plus α1-adrenoceptor antagonists were 44 % more likely to spontaneously expel the stone (RR 1.44, p<0.001, NNT 4), and stone expulsion incidence increased significantly (risk differences (RD) 0.28, p<0.001)12.

In the study conducted by Dellabella et al, the efficacy of Tamsulosin 400 mcg was evaluated to a total of 60 consecutive symptomatic patients with stones located in the juxtavesical tract of the ureter for 4 weeks13 . Patients were randomized to 2 treatment groups. Group 1 (30 patients): under floroglucine-trimetossibenzene tablets 3 times daily for a maximum of 4 weeks and group 2 (30 patients): treated with Tamsulosin 400 mcg tablets daily for a maximum of 4 weeks. The stone expulsion rate was 70% for group 1 and 100% for group 2 (p = 0.001). Mean stone size was 5.8 and 6.7 mm, respectively (p = 0.047). Tamsulosin 400 mcg tablets increased the expulsion rate and decreased the expulsion time, the need for hospitalization and endoscopic procedures, and provided particularly good control of colic pain.

Recently, MET has shown encouraging results in facilitating spontaneous clearance of lower ureteral stones as well as fragments ESWL for renal and ureteral stone14-18.

α1-Adrenoceptor antagonists like Tamsulosin was evaluated in its role in stone clearance in patients with upper ureteral stone after Extracorporeal shock wave lithotripsy (ESWL)19. ESWL has been recommended as first-line treatment modality for upper ureteral stone in several studies with a success rate of 80% to 90%20-22

While in the study, the role of Tamsulosin in clearance of upper ureteral calculi after ESWL conducted by Singh et al, this randomized controlled trial was performed on 117 patients with a single upper ureteral stones undergoing ESWL23. The study group received 400 mcg Tamsulosin daily while the control group received hydration and analgesic demand for a maximum of 3 months. Follow-up visits were performed at 1,2, and 3 months after ESWL. Efficiency of Tamsulosin was evaluated in terms of success rate, time for expulsion of fragments, number of ESWL sessions, incidence of steinstrasse, and pain intensity. Clearance rate were higher after 1, 2, and 3 months in the Tamsulosin group than the control group (85%, 89.8%, and 91.5% versus 70.6%, 79.3%, and 86.2% ; p = 0.01, p = 0.11, and p = 0.34, respectively).

The study by Singh et al concluded indicates that Tamsulosin helps in the clearance of upper ureteral stones after 1 month of ESWL, particularly stones with size of 11 to 15 mm with less requirement of ESWL sessions and analgesics.

One meta-analysis reviews the evidence for the use of α1-adrenoceptor antagonists after ESWL in enhancing the effectiveness of ureteral stone clearance. 7 trials (484 patients) met the predefined criteria. The pooled absolute risk difference of clearance rate was 16% (95% CI: 5% to 27%) in Tamsulosin group, i.e. an average of six patients have to be treated with Tamsulosin after ESWL to achieve clearance in one. Subgroup analysis for the 6 studies that used a dose of 0.4 mg Tamsulosin showed a pooled risk difference of 19 % (95% CI: 10% to 29%). The expulsion time was analyzed in three studies and the pooled mean difference was 8 days (95% CI: -3 to 20 days) in Tamsulosin group. Pain and analgesic usage were reported to be lower with Tamsulosin19.

Furthermore, the European Urology Association (EAU) 2010 guidelines on Urolithiasis determined in a panel meeting two randomized controlled trials. The panel attempted to evaluate whether α1-adrenoceptor antagonists provide superior stone passage compared to nifedipine24. When non-hierarchical meta-analysis on these two studies was done, it showed that Tamsulosin provided a stone-passage improvement increase to 16% (95% CI: 7% to 26%) with a statistically significant.

In the American Urological Association (AUA) guidelines on Urolithiasis. For ureteral stones <10 mm in diameter, there is growing evidence that MET limits pain and accelerates the spontaneous passage of ureteral stones as well as stone fragments generated with ESWL25.

With all the above studies, it can be concluded that Tamsulosin 400 mcg is an effective treatment for the medical management of ureteral stones and helps in the clearance of ureteral stones after ESWL.

Tamsulosin 400 mcg has shown to be effective and safe in Asian patients with ureteral stones26 as well as benign prostatic hyperplasia (BPH).

The stone clearance rate was also significantly greater with the patients treated with Tamsulosin Oral Controlled Absorption System (Harnal OCAS) 400 mcg than those in the standard care group at 4 (73.4% vs. 55.9%, respectively; p<0.001) and 12 (91.3% vs. 74.6%, respectively; p<0.05) weeks. Tamsulosin (Harnal OCAS) 400 mcg treatment was also associated to a lower interval to the elimination of stone fragments (p<0.001), a significantly lower rehospitalisation rate (p<0.001), and a significantly lower proportion of patients with acute renal colic (p<0.05) than standard care alone. No severe adverse events leading to treatment discontinuation were observed. Adjuvant treatment with Tamsulosin (Harnal OCAS) 400 mcg, in addition to standard treatment with steroids and analgesics, improved the outcome of ESWL27.

List of References:




(year/page reference)


Ljunghall S, Renal Stone Diseases, Studies of Epidemiology and Calcium Metabolism

Scan J Urol Nephrol 1977 ; 41 : –6-38


Pak CY, Resnik MI, Preminger GM. Ethnic and Geographic Diversity of Stone Disease

Urology 1997 ;  50 , 504-07


Stamatelou KK, Francis ME, Jones CA, Nyberg LM, Curhan GC. Time Trends in reported prevalence in Kidney Stones in the US, 1976-1994

Kidney International 2003; 63, 1817-23


Tiselius HG, Epidemiology and Medical Management of Stone Disease by Tiselius HG

BJU International 2003; 91:758-67


Hubner WA, Irby P, Stroller MI, Natural history and current concepts for the treatment of small ureteral calculi

European Urology 1993 24: 172-76


Miller OF, Kane CJ, Time to stone passage for ureteral calculi : A guide for patient education

J Urol 1999; 162, 688-91


Sigala S, Dellabella M,Milanese G, et al., Evidence for the presence of α1-adrenoreceptor subtypes in the human ureter

Neurourol Urodyn 2005, 24: 142-148


Obara K, Takeda M, Shimura H, et al., Alpha-1 adrenoceptor subtypes in the human ureter. Characterization by RT-PCR and in situ hybridization

J Urol 1996; 155 (suppl); 472A: abstract: 646


Sasaki S, Tomiyama Y, et al., Characterization of α1-adrenoceptor subtypes mediating contraction in human isolated ureters.

Urology 2011; 77: 762.e13-762.e17.


Hollingsworth JM, Rogers MA, Kaufman SR, et al., Medical therapy to facilitate urinary stone free passage: A meta-analysis

Lancet 2006; 368: 1171-9


Singh A, Alter H., et al., A Systematic Review of medical Therapy to Facilitate Passage of ureteral Calculi.

Annals of Emergency Medicine 2007;50:552-563


J. Kellogg Parsons, Lori Ann Hergan, Kyoko Sakamoto, Charles Laken, Efficacy of alpha-blockers for the Treatment of Ureteral Stones.

Journal of Uro 2007 ; 177 : 983-987


Dellabella M, Milanese G, Muzzonigro G, Efficacy of Tamsulosin in the Medica Management of juxtavesical ureteral stones

Journal of Uro 2003 ; 170 : 2202-2205


Hollingsworth JM, Rogers MA, Kaufman SR, et al., Medical therapy to facilitate urinary stone passage: a meta-analysis.

Lancet 2006; 368: 1171-9


Gravina GL, Costa AM, Ronchi P, et al., Tamsulosin treatment increases clinical success rate of single extracorporeal shock wave lithotripsy of renal stones.

Urology 2005; 66: 24-8


Kupeli B, Irkilata L, Gurocak S, et al., Does tamsulosin enhance lower ureteral stone clearance with or without shock wave lithotripsy?

Urology 2004;64:1111-5


Bhagat SK, Chacko NK, Kekre NS, Gopalakrishnan G, Antonisamy B, Devasia A. Is there a role for tamsulosin in shock wave lithotripsy for renal and ureteral calculi?

J Urol. 2007;177;2185-8


Naja V, Agarwal MM, Mandal AK, et al., Tamsulosin facilitates earlier clearance of stone fragments and reduces pain after shockwave lithotripsy for renal calculi: results from an open-label randomized study.

Urology 2008;72:1006-11


Yenfang Z, Diederck D, Maroeska MR, Tycho ML, Alpha blockers to assist Stone Clearance after Extracoporeal Shockwave Lithotripsy (ESWL) : a meta-analysis

BJU International 2009: 106; 256-261


Mitre AL, Chambo JL, Nahas WC, et al., Ureteral calculi: extracorporeal shock-wave lithotripsy performed in situ on an outpatient basis.

World J Urol. 1992; 10: 213-5


Mogensen P, Andersen JT. Primary in situ extracorporeal shock wave lithotripsy for ureteral calculi.

Scand J Jrol Nephrol Suppl. 1994; 157:159-63


Gananapragasam VJ, Ramsden PD, Murthy LS, Thomas DJ, Primary in situ extracorporeal shock wave lithotripsy in the management of ureteric calculi: results with a third-generation lithotripter.

BUJ Int. 1999; 84: 770-4


Santosh KS, Devendra SP., Mahavir SG., Jag MI., Sachit S., Role of Tamsulosin in Clearance of Upper Ureteral Calculi After Extracorporeal Shock Wave Lithotripsy

Urol J 2011;8:14-20


Turk C., Knoll T., et al., EAU Guidelines on Urolithiasis (updatd March 2011)

European Association of Urology Guidelines on Urolithiasis 2011; 978 -90


American Urological Association, Comprehensive Guidelines on Urolithiasis 2007 (updated 2011)

American Urological Association, Guidelines on Urolithiasis 2011; 31-33


Lojanapiwat B, Kochakarn W , et al., Effectiveness of Low-dose and Standard-dose Tamsulosin in the treatment of Distal Ureteric Stones : A Randomized Controlled Study

The Journal of International Medicine Research 2008 : 36; 529-536


Marin I. Georgiev, et al., Efficacy of Tamsulosin Oral Controlled Absorption System After Extracorporeal Shock Wave Lithotripsy to Treat Urolithiasis

Urology 2011:78; 1023-1028