Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL

Allopurinol Effect on MDA,NO,KIM-1 Urine Levels, RI and Renal Elastography in Kidney Stone Patients Post ESWL

The Effect of Allopurinol on Malondialdehyde, Nitric Oxide, Kidney Injury Molecule-1 Urine Levels, Resistive Index and Renal Elastography in Kidney Stone Patients After Extra Corporeal Shockwave Lithotripsy

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.

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.

Level of Malondialdehyde (MDA), Nitric Oxide (NO), and Kidney Injury molecule-1 (KIM-1) in urine were determined by quantitative double antibody sandwich direct ELISA

Level of Malondialdehyde (MDA), Nitric Oxide (NO), and Kidney Injury molecule-1 (KIM-1) in urine were determined by quantitative double antibody sandwich direct ELISA

Resistive Index (RI) change of the interlobar artery and elastography of the ipsilateral renal focal zone at ESWL

Resistive Index (RI) change of the interlobar artery and elastography of the ipsilateral renal focal zone at ESWL

Inclusion Criteria: Patient with renal stone who meet ESWL criteria Age 18 to 59 years old Consent to join this study Exclusion Criteria: Patient with Diabetes Melitus Patient with hypertension Patient with Chronic Kidney Disease stage IV and stage V Patient with urinary tract infection Patient with obesity Patient with uric acid more than 9mg/dL

We are no going to share any individual participant data (IPD) considering Participant's Confidentiality.

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