Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL
Condition: Kidney Calculi
MeSH terms: Kidney Calculi; Nephrolithiasis; Calculi
Study type: Interventional
Phase: Phase 4

Summary: 
      Extracorporeal shock wave lithotripsy (ESWL) is accepted as the first treatment choice for
      most urinary stones. Still, it has adverse effects on the kidneys. The mechanism underlying
      the shock wave induced renal injury is not entirely understood, and oxidative stress has been
      speculated to be involved in this process. The Investigator evaluated the role of
      allopurinol, which works as a xanthine oxidase inhibitor and free radical scavenger in renal
      protection against oxidative effects of ESWL. In a randomized, double-blind
      placebo-controlled trial, a total of 70 patients with renal stones undergoing ESWL were
      randomly assigned to 2 groups. Group 1 receive allopurinol, and group 2 receive a placebo.
      Allopurinol 300mg was given orally for a total of 3 days, beginning a day before ESWL. The
      urinary excretion of malondialdehyde (MDA), nitric oxide (NO), and kidney injury molecule-1
      (KIM-1) were determined by quantitative double antibody sandwich direct ELISA at baseline
      before ESWL then repeatedly two h, and 24 h after ESWL. The resistive index (RI) change of
      the interlobar artery was asses along with the measurement of the shear wave velocity (SWV)
      in the focal zone of the treated kidney before, two weeks, and four weeks after ESWL.
      Multivariate analyses were performed using repeated measure ANOVA to control covariates.
    

Detailed description: 
      Subjects with kidney stones who met the criteria were given a detailed explanation about this
      study by the research team, then followed by signing the informed consent. History was taken
      along with physical examination, complete blood count, Bun, creatinine, uric acid, urinalysis
      and also anthropometric measurements (weight and height). Then each subjects got one of the
      intervention drugs, either allopurinol 300mg or placebo. Allopurinol 300 mg was finely
      grounded and put into gelatin capsules. The placebo was made by using Saccharum lactis
      material which was inserted into a gelatin capsule as well. The shape, color, texture, and
      weight of the placebo capsules were made the same as the drug allopurinol. Allopurinol
      capsules and placebo were made by the Pharmacy section of Sanglah Hospital.

      Subjects were randomly allocated using a permuted block method into the allopurinol or
      placebo group. Each subject received one type of capsule consisting of 3 capsules containing
      300 mg allopurinol or placebo taken the day before ESWL, 2 hours before ESWL, and the day
      after ESWL.

      The study was conducted double-blind where the researcher, subject, data collector, outcome
      adjudicator, and data analyst did not know the type of treatment. Medicines are given in
      sealed envelopes using an undisclosed code that will be uncovered at the end of the study.

      For the preparation of ESWL subjects; each subjects got infusion of 0.9% NaCl with 20 drops
      per minute, ondansetron 8 mg i.v., pethidine bolus 50 mg i.v., followed by drip pethidine 50
      mg and ketorolac 30 mg given in 500 ml NaCl 0.9% with 20 drops of 20 drops per minute.

      The Investigator performed ESWL using a Siemen litostar vario which uses an electromagnetic
      generator. The number of shock waves given is 2500-3000 shock waves per session. The given
      shock wave strength is slim to 2 J in the initial 200 shock wave followed by 3 to 3.5 J in
      the remainder of the shock wave. The given shock wave frequency is 60 x/minute.

      Urine samples were taken aseptically using the mid-portion method in the amount of 10 ml for
      examination of biomarkers KIM-1, NO, and MDA one hour before ESWL. Furthermore, the urine
      sample was taken 10 ml two hours after ESWL and one day after ESWL. Examination time after
      ESWL is calculated from the end of the ESWL session.

      RI examination and renal SWV elastography were performed one hour before ESWL, followed by
      two weeks and one month after ESWL by the same radiology specialist.

      Subject compliance with medication is evaluated based on the number of capsules taken from
      the entire drug administered. If the number of capsules taken is less, the subject will be
      excluded from the analysis. Adverse events or drug side effects are defined as unexpected
      events during the study, such as experiencing procedure-related complications or being
      allergic to allopurinol. The Investigator evaluated the subjects every week after ESWL to
      assess tolerance and possible side effects.

      If there was any drug side effects or serious adverse events(SAE), the subjects were reported
      to the ethics committee as soon as possible, less than 24 hours from the first time they were
      discovered, and actions were carried out as quickly as possible until the series of events
      ends. SAE was written in detail on the SAE form, including the following; when it was first
      discovered, the manifestation of the incident, the conditions before the incident, the
      handling of the event, and the outcome.

      If the subject experiences side effects such as allergic reactions (redness of the skin,
      swelling of the eyes or mouth) and severe gastrointestinal disturbances (vomiting, diarrhea),
      the subject will be excluded from the analysis. The subject will also be excluded from the
      analysis if they experience complications related to ESWL procedure such as ureteral
      obstruction, pain (VAS > 5), or there were signs of infection. Subjects will be evaluated
      when visiting the hospital according to schedule, telephone contact, or by making a home
      visit.

      The envelope of intervention data will be opened after data analysis, witnessed by an
      independent team, namely the Sanglah Hospital pharmacy and the Sanglah Hospital research
      division.
    

Intervention name(s): Allopurinol Tablet 300 mg; Control Group
Intervention type(s): Drug; Drug
Intervention description(s): Allopurinol 300mg was given orally for a total of 3 days, beginning a day before ESWL.; Placebo was given orally for a total of 3 days, beginning a day before ESWL.
Other intervention name(s): Allopurinol; Placebo
Intervention MeSH terms: Allopurinol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment