Efficacy of Isosorbide in Post Extra Corporeal Shock Wake Lithotripsy Stone-Free Time

EXTENDED ABSTRACT

Background

Kidney stone disease is a common urinary disorder and may present with acute renal colic, hematuria, nausea, vomiting, or obstruction of urinary flow [1, 2]. Treatment is selected according to stone size, location, composition, clinical factors, available equipment, and operator experience [4]. Extracorporeal shockwave lithotripsy (ESWL) is a noninvasive and comparatively cost-effective approach. Although ureteroscopy may be more effective for distal ureteral calculi [5,6], ESWL remains an important option for renal-pelvis stones; however, lower stone-free rates and failure to clear fragments can prolong symptoms or contribute to infection, obstruction, and impaired renal function [7, 9].

Pharmacologic measures that facilitate fragment passage have therefore been investigated. Tamsulosin has been associated with shorter stone-passage time [9, 10], and hydrochlorothiazide has also been studied after ESWL [11]. Nitrates can relax smooth muscle, and limited studies have examined isosorbide or glyceryl trinitrate for renal colic and ureteral stone passage [12–14]. Isosorbide dinitrate acts principally through smooth-muscle relaxation and vasodilation [15], while reviews of ureteral pharmacology have identified smooth-muscle-directed drugs as potential expulsive therapies [16]. Because the authors found no previous study evaluating isosorbide dinitrate specifically as an adjunct to ESWL, this trial aimed to determine whether isosorbide dinitrate reduces the time required for passage of renal-pelvis stone fragments after ESWL.

Methods

This clinical trial was conducted in 2019 among patients with renal-pelvis stones referred to the ESWL Department of Moradi Hospital, Rafsanjan, Kerman, Iran. The study population comprised all eligible referrals during the study period, with convenience sampling and a sample size equal to the available population. Eligibility criteria included body weight below 100 kg, renal-pelvis stone size up to 20 mm, no history of renal failure, previous lithotripsy, renal surgery, previous stone passage, use of diuretics, or use of smooth-muscle relaxants, and absence of moderate or severe hydronephrosis. Baseline demographic and stone-related information included age, sex, weight, stone size and number, and side of involvement, based on ultrasonography and kidney-ureter-bladder radiography performed by the study radiologist.

Before ESWL, intravenous access was obtained and pethidine was administered for analgesia. Patients were positioned supine, the stone was localized by ultrasonography and radiography, and the focal point of the lithotripter was aligned with the stone. Approximately 3,000 shock waves at a reported power of 16–18 kW were delivered during a session lasting about one hour. A Dornier Compact Sigma system (Dornier MedTech, Munich, Germany) was used. After one hour of recovery and standard discharge education, patients were assigned as randomly as possible, after attempts to match groups for age, sex, weight, and stone size, to receive either isosorbide dinitrate 20 mg twice daily for two weeks or a matching placebo for two weeks. Patients, the radiologist, radiology technologist, and ward nurse were unaware of treatment allocation; only the treating physician knew the assigned treatment.

Each participant received a checklist on which the exact day and hour of every stone-fragment passage was recorded; the time of the last passage was used for analysis. At two weeks, as specified by the study protocol [17], ultrasonography and repeat abdominal radiography were used to determine residual stone size, location, and number. Complete absence of fragments was considered successful lithotripsy; persistence of any fragment was considered failure. Data were analyzed in SPSS version 16 using descriptive statistics and Mann-Whitney and Kruskal-Wallis tests, with statistical significance set at 0.05. The study was approved by the Ethics Committee of Rafsanjan University of Medical Sciences (IR.RUMS.REC.1397.200), registered as IRCT20150317021497N9, and all participants provided written informed consent.

Results

Of 182 enrolled patients, 176 completed the study, yielding a 96.7% response rate. The final sample included 98 men (55.7%) and 78 women (44.3%), with a mean age of 51.0±12.0 years (range, 21–75 years). Eighty-seven patients (49.4%) received isosorbide and 89 (50.6%) received placebo. The groups did not differ significantly by sex (P=0.893), age (P=0.523), or weight (P=0.729). Mean stone size was 14.79 mm, mean body weight was 68.20±9.18 kg, and the overall mean stone-passage time was 4.5±1.14 days (range, 1–7 days).

The primary finding was a significantly shorter mean stone-passage time with isosorbide than with placebo: 4.21±1.05 versus 4.79±1.16 days (P=0.001). Among men, the corresponding means were 4.24±1.17 and 4.92±1.14 days (P=0.007), whereas the difference among women was not statistically significant (4.17±0.89 vs 4.61±1.18 days; P=0.086). In patients aged 36–55 years, passage time was 4.15±0.97 days with isosorbide and 4.74±1.26 days with placebo (P=0.021). For stones measuring 16–20 mm, passage time was 3.93±1.02 versus 4.73±1.24 days (P=0.011), while differences in the smaller stone-size categories were not significant. Among participants weighing 61–80 kg, the means were 4.07±0.98 and 4.78±1.21 days (P=0.001); no significant difference was observed in those weighing 48–60 kg (P=0.648). Passage time was also shorter in the isosorbide group for right-sided stones (4.13±1.02 vs 4.84±0.98 days; P=0.008) and left-sided stones (4.25±1.07 vs 4.76±1.23 days; P=0.036).

Table 1. Comparison of stone-passage time in patients treated with isosorbide and placebo by sex, age, stone size, weight, and stone side.

Overall ESWL success was 77.8%. Successful clearance occurred in 68 of 87 patients in the isosorbide group (78.2%) and 69 of 89 patients in the placebo group (77.5%), with no significant between-group difference (P=0.919). Thus, isosorbide shortened the time to passage of fragments without materially changing the proportion of patients who were stone free at the two-week assessment.

Table 2. Frequency of lithotripsy success and sex in the isosorbide and placebo groups.

Conclusion

Adjunctive isosorbide dinitrate after ESWL reduced the time required for passage of renal-pelvis stone fragments compared with placebo, while the overall lithotripsy success rate remained similar between groups. The reduction was especially evident in several patient and stone subgroups, including patients aged 36–55 years and those with 16–20 mm stones. The authors concluded that isosorbide may be used alongside other post-ESWL treatments to facilitate urinary stone passage, while noting that additional studies are needed to confirm the finding.

Keywords: Isosorbide, Lithotripsy, Stone Passage

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