Effect of Allopurinol on Markers of Mineral and Bone Metabolism

Not Applicable

Completed

• Conditions: Chronic Kidney Diseases; Osteodystrophy; Uric Acid Concentration, Serum, Quantitative Trait Locus 7
• Interventions: Drug: Allopurinol

• Registration Number: NCT05601271
• Lead Sponsor: University of Sao Paulo General Hospital

Brief Summary

Hyperuricemia is a common condition in patients with chronic kidney disease (CKD) in the glomerular filtration rate. Recently, it has been suggested that uric acid is related to a mineral and bone disease of CKD (CKD-MBD) since the high concentration of uric acid is associated with the harmful effect of vitamin D. The proof of concept of the association between acid uric acid and CKD-MBD is based on a prospective study (sample size 6) that observed, after 1 week of use of allopurinol, an increase in the concentration of 1,25(2D, a result independent of the concentration of calcium, phosphorus, 25(OH)D and PTH. An experimental study found that hyperuricemia could modify the expression of the 1α-hydroxylase enzyme, consequently reducing 1,25(OH). The current study aims to evaluate the action of allopurinol on CKD-MBD biomarkers (25(OH)-vitamin D, 1,25(OH)2D, FGF-23, PTH, calcium and phosphorus). We hypothesize that allopurinol can improve serum levels of 1,25(OH) 2D and PTH. This is a controlled, randomized, double-blind study, defined as a filtration rate \< 60ml/1.73 m², according to the CKD-EPI equation. Inclusion criteria: patients with stages III, IV and V CKD who are not on dialysis with a serum level of 25(OH)-vitamin D \>20 ng/ml. Exclusion criteria: Patients diagnosed with gout, undergoing treatment with allopurinol, patients already in use and drugs with sensitivity to the drug. Based on a previous study, we calculated a sample for 2 groups (placebo and drug) with pre and post-measurements (a total of 4). Considering a standard deviation of 4 and a difference of 7 in the treated group, 3 in the placebo group, and an alpha error of 5%, we calculated a sample of 25 patients in each arm.

Detailed Description

In this randomized double-blind study, patients receive allopurinol or a placebo for 3 months.

Dependent variables: 25(OH)-vitamin D, 1,25(OH)2D, FGF-23, PTH, calcium and phosphorus Population: stage 3, 4 or 5 CKD on conservative management at the Nephrology Service of Hospital das Clinicas HCFMUSP, Sao Paulo, Brazil.

The same physician will follow patients. Adverse effects will be recorded.

Study Timeline

• Study Start: 2021-03-01
• Study First Submitted: 2022-10-26
• Study First Submitted QC: 2022-10-26
• Study First Posted: 2022-11-01
• Status Verified: 2024-12
• Primary Completion: 2025-03-01
• Study Completion: 2025-03-01
• Last Update Submitted: 2025-03-27
• Last Update Posted: 2025-04-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

stage 3, 4 or 5 CKD on conservative management

Exclusion Criteria

• allergy to allopurinol
• current treatment with allopurinol
• Gout

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	Allopurinol	pills exactly as the drug will be delivered to participants. Instructions will be made to take the pill once a day.
Allopurinol	Allopurinol	pills exactly as the placebo will be delivered to participants. Instructions will be made to take the pill once a day.

Primary Outcome Measures

Name	Time	Method
FGF-23	3 months	Reduction of FGF-23
Klotho	3 months	Increase in alpha Klotho
1,25 dihydroxivitamin D	3 months	Increase in 1,25 dihydroxivitamin D

Trial Locations

Locations (1)

Hospital das Clinicas HCFMUSP; 🇧🇷 São Paulo, SP, Brazil