Summary of Removal of Small, Asymptomatic Kidney Stones and Relapse Rates
By: Mathew D. Sorensen, MD, MS, FACS; Jonathan D. Harper, MD; Michael S. Borofsky, MD; Michael R Bailey, PhD; James E. Lingeman, MD, FACS | Posted on: 01 Dec 2022
The 73 study participants (38 treatment group, 35 control group) were already undergoing endoscopic stone treatment with ureteroscopy or percutaneous nephrolithotomy for a primary stone, defined as large kidney or obstructing ureteral stones. All these patients also had secondary stones, defined as small (≤6 mm), asymptomatic stones located in the contralateral kidney for a primary renal stone, or either the ipsilateral or contralateral kidney of a primary ureteral stone. We prospectively randomized these patients to either have their primary and secondary stones treated (treatment) or just the primary stones (control).1,2 The primary outcome was relapse, which was measured by future emergency department (ED) visits, surgeries, and stone growth. After a median 4.2 years of follow-up, the treatment group had 82% lower risk of relapse (HR 0.18, 95% CI 0.07-0.44), with 16% relapses (6 of 38) in the treatment group and 63% relapses (22 of 35) in the control group (see Figure and Table). The treatment group also had 75% longer time to relapse than in the control group (1,631.6 days [SE 72.8] vs 934.2 [SE 121.8]). The removal of the small asymptomatic renal stones in the treatment group added a median of 25.6 (IQR 18.5-35.2) minutes to surgery. There were no differences between groups in acute ED visits within 2 weeks after surgery, all of which occurred because of stent pain. Eight participants in the treatment group and 10 in the control group reported passing stones. Treatment of secondary stones did not affect new stone formation (37% in the treatment group vs 43% in the control group). Our conclusion was among patients undergoing surgical removal of ureteral or significant kidney stones, removal of small, asymptomatic kidney stones during their surgery reduced relapse at the cost of about 25 minutes of surgery time without increasing surgery-related ED visits.
Our work was supported by NIH NIDDK grant P01 DK043881 and from resources through the Veterans Affairs Puget Sound Health Care System. The ClinicalTrials.gov number was NCT02210650. The 4 sites were University of Washington (Principal Investigator [PI]: J.D. Harper), VA Puget Sound Health Care System (PI: M.D. Sorensen), University of Minnesota (PI: M.S. Borofsky), and Indiana University (PI: J.E. Lingeman).
The relapse rate of our control group (63% in 52 months) is similar to rates of relapse of untreated symptomatic stones published in the AUA guidelines (43% relapse in 32 months).3 Likewise, the added time to surgery, 25 minutes, is similar to the time, 16 minutes, added by removing asymptomatic kidney stones during ipsilateral ureteroscopy for a ureter stone.4 Also, our data add to a growing body of evidence that supports the efficacy and safety of single-setting treatment of ureteral and kidney stones, combining ureteroscopy and percutaneous nephrolithotomy, and performing bilateral modern-era endoscopic procedures.5-7
Some limitations of our study include that our study size was relatively small, and the small number of non-White participants attenuated generalization to other groups. Surgeons were unblinded as to treatment group post-procedure, but this limitation is likely counterbalanced to some degree by the shared patient care model and high rates of preventive evaluation in both study arms. All surgeons were fellowship trained and surgeon skill was not tested, and including a quality of life score may have been interesting.
Table. Relapse—primary effectiveness outcome
N = 38 (%)
N = 35 (%)
|OR (95% CI)||P value|
|Future surgeries||2 (5)||9 (26)||0.16 (0.03-0.81)||.02|
|Future ED visita||2 (5)||10 (29)||0.14 (0.03-0.69)||.01|
|Total surgeries or ED visit, or both||4 (11)||15 (43)||0.16 (0.05-0.54)||.003|
|Growth of study stones||3 (8)||13 (37)||0.15 (0.04-0.57)||.0039|
|Total surgeries, ED visits, or growth of study stones||6 (16)||22 (63)||0.11 (0.04-0.34)||< .0001|
|Abbreviations: CI, confidence interval; ED, emergency department.|
Overall, at the time of surgery for a primary kidney or ureteral stone, additional treatment of small, asymptomatic stones that are located in a separate area is supported by our data. The financial comparison completed in response to the paper reviews was that not removing stones was 2.4 times more expensive based on 100 surgical procedures with 25 additional minutes at $36 per minute,8 and would add $90,000 compared with an estimated $217,000 for 63 ED visits at an average cost of $3,437 per ED visit.9 Toward Dr Streeper’s and Dr Hsi’s debate on the benefit of preemptive endoscopic surgery to remove even small asymptomatic renal stones,10,11 a single relapse event per patient might well justify prophylactic surgery on all patients, and in fact our control group of 35 patients had 36 relapse events.
Lastly, we are privileged to consider and contemplate prophylactic removal of additional stones because of the improvements and advancements in endoscopic and other technologies to treat stones. Despite these advances, residual fragments remain after 30%–65% of procedures and were present in 18% (7 of 38) of the treatment group in the current study including all 6 relapses.12,13 Like many others, our team continues to research improving efficacy and reducing risk of treating stones, which will further tip the scales toward earlier intervention. One particular focus is the use of noninvasive transcutaneous ultrasound to break and reposition stones and fragments to facilitate their clearance in awake patients. We recently demonstrated a median fragmentation of 90% of stone volume to <2 mm in 10 minutes, which was reported in The Journal of Urology®,14 and subsequently reported the data seen treating ureter stones in the ED or clinic in awake, nonanesthetized patients.15 Our randomized controlled trial on clearing residual fragments with ultrasonic propulsion will soon be submitted. As technologies lower the barrier to treatment, especially with little or no anesthesia and a transition out of the operating room and into the clinic, we expect the barriers to prophylactic treatment will similarly decrease.
- Sorensen MD, Harper JD, Borofsky MS, et al. Removal of small, asymptomatic renal stones and relapse rates. N Engl J Med. 2022;387(6):506-513.
- Sorensen MD, Bailey MR, Lungeman JE. Correspondence to Removal of small, asymptomatic renal stones and relapse rates, N Engl J Med. 2022; in press.
- Assimos D, Krambeck A, Miller NL, et al. Surgical management of stones: American Urological Association/Endourological Society Guideline, PART I. J Urol. 2016;196(4):1153-1160.
- Bilgasem S, Pace KT, Dyer S, Honey RJ. Removal of asymptomatic ipsilateral renal stones following rigid ureteroscopy for ureteral stones. J Endourol. 2003;17(6):397-400.
- Cocuzza M, Colombo JR., Ganpule A, et al. Combined retrograde flexible ureteroscopic lithotripsy with Holmium YAG laser for renal calculi associated with ipsilateral ureteral stones. J Endourol. 2009;23(2):253-257.
- Goldberg H, Holland R, Tal R, Lask DM, Livne PM, Lifshitz DA. The impact of retrograde intrarenal surgery for asymptomatic renal stones in patients undergoing ureteroscopy for a symptomatic ureteral stone J Endourol. 2013;27(8):970-973.
- Fiscus G, Marien T, Tangpaitoon T, Kuebker J, Herrell SD, Miller NL. Single session bilateral vs staged bilateral ureteroscopy for nephrolithiasis: an assessment of safety and efficacy. Urology. 2019;123:64-69.
- Childers CP, Maggard-Gibbons M. Understanding costs of care in the operating room. JAMA Surg. 2018;153(4):e176233.
- Caldwell N, Srebotnjak T, Wang T, Hsia R. How much will I get charged for this? Patient charges for top ten diagnoses in the emergency department. PLoS One. 2013;8(2):e55491.
- Bhalla RG, Hsi RS. Should asymptomatic renal stones be surgically treated? Pro treatment. J Endourol. 2021;35(5):567-569.
- Streeper NM. Should asymptomatic renal stones be surgically treated? Pro-observation. J Endourol. 2021;35(5):570-572.
- Feinstein L, Matlaga B. Urologic Diseases in America. US Government Printing Office, 2018; NIH Publication No. 12-7865;12-13.
- Pearle MS, Lingeman JE, Leveillee R, et al. Prospective randomized trial comparing shock wave lithotripsy and ureteroscopy for lower pole caliceal calculi 1 cm or less. J Urol. 2008;179(5 suppl):S69-S73.
- Harper JD, Lingeman JE, Sweet RM, et al. Fragmentation of stones by burst wave lithotripsy in the first nineteen humans. J Urol. 2022;207(5):1067-76.
- Hall MK, Thiel J, Dunmire B, et al. First series using ultrasonic propulsion and burst wave lithotripsy to treat ureteral stones. J Urol. 2022;208(5):1075-1082.