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#18 Is there more to medical management of renal stones than analgesia?


CLINICAL QUESTION
In patients with renal stones eligible for observation, does medical expulsion therapy (MET) improve passage of stones and other clinically relevant outcomes?


BOTTOM LINE
Best evidence indicates that nifedipine does not help pass renal stones. Furthermore, there is real doubt if alpha-blockers like tamsulosin provide any benefit (except perhaps in stones >5mm).



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EVIDENCE
New evidence suggest no meaningful benefit. 
  • Largest Randomized Controlled Trial (RCT)1,2 of 1,167 patients with ureteric stone <10 mm (75% <5 mm, 65% distal ureter) randomized to nifedipine sustained-release 30 mg, tamsulosin 0.4 mg or placebo once daily for up to four weeks. 
    • No difference between groups in: 
      • Spontaneous stone passage (~80% in each group). 
        • Possible effect with tamsulosin in stones >5 mm in distal ureter, (~10% improved passage at four weeks), but not significant. Nothing for nifedipine.   
      • Time to stone passage, analgesic use, or self-reported health status. 
    • More discontinuation due to adverse events with nifedipine [Number Needed to Harm (NNH)=10] and tamsulosin (NNH=25) versus placebo.2 
  • Earlier Cochrane review3 of 32 studies of 5,864 patients (largest meta-analysis=2,378 patients). 
    • Alpha-blockers (most commonly tamsulosin) versus standard therapy. 
      • Increased stone passage: Relative Risk (RR) 1.48 (1.33-1.64). 
        • Effect reduced and (barely) no longer statistically significant when limited to six placebo-controlled trials: RR 1.22 (0.99-1.51). 
      • Reduced risk of hospitalization, time to stone passage, number of pain episodes, analgesic use. 
        • Ndifference in placebo-controlled trials. 
      • Possibly greater efficacy with larger stones: >5 mm (RR 1.68) versus  ≤5 mm (RR 1.41) 
    • Alpha-blockers increased stone passage versus nifedipine RR 1.19 (1.05-1.35), low-quality evidence.4 
  • Previous meta-analyses5-7 that found benefit from MET with alpha-blockers or nifedipine included mostly non-blinded trials and did not evaluate trial quality or account for his risk of bias. 
Context:  
  • Canadian,8 European,9 and US10 guidelines for urolithiasis recommend MET as an option in: 
    • Newly diagnosed ureteral stone <10 mm in patients without need for urgent urological intervention. 
    • Patients with well-controlled pain who are not septic, have good renal function, and who are followed with periodic imaging to monitor stone position and assess hydronephrosis. 
    • All except the Canadian guidelines were published before the largest RCT. 
  • MET dosing:1-3 Tamsulosin 0.4 mg once daily until stone passed or for four weeks (whichever occurs first). 
 updated aug 25 2016 by ricky


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Author(s):

  • G. Michael Allan MD CCFP
  • Michael R Kolber MD CCFP MSc

1. Pickard R, Starr K, MacLennan G, et al. Lancet. 2015; 386:341-9.

2. Pickard R, Starr K, MacLennan G, et al. Health Technol Assess. 2015; 19(63).

3. Campschroer T, Zhu Y, Duijvesz D, et al. Cochrane Database Syst Rev. 2014; 4:CD008509.

4. Ye Z, Yang H, Li H, et al. BJU Int. 2011; 108:276-9.

5. Hollingsworth JM, Rogers MA, Kaufman SR, et al. Lancet. 2006; 368:1171-9.

6. Singh A, Alter HJ, Littlepage A. Ann Emerg Med. 2007; 50:552-63.

7. Seitz C, Liatsikos E, Porpiglia F. Eur Urol. 2009; 56(3):455-71.

8. Ordon M, Andonian S, Blew B, et al. Can Urol Assoc J. 2015; 9:E837-51.

9. Guidelines on Urolithiasis. European Association of Urologist. Available for download at: http://uroweb.org/wp-content/uploads/22-Urolithiasis_LR_full.pdf. Last accessed: August 25 2016.

10. Preminger GM, Tiselius HG, Assimos DG, et al. J Urol. 2007; 178:2418-34.

Authors do not have any conflicts of interest to declare.