Effect of Allopurinol on Markers of Mineral and Bone Metabolism

Effect of Allopurinol on Markers of Mineral and Bone Metabolism in Patients in With Chronic Kidney Disease: a Randomized Double-blind Study

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Kidney Diseases; Osteodystrophy; Uric Acid Concentration, Serum, Quantitative Trait Locus 7
• Intervention / Treatment: Drug: Allopurinol

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 Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • São Paulo, SP, Brazil, 05403000
      • Hospital das Clínicas HCFMUSP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: stage 3, 4 or 5 CKD on conservative management

-

Exclusion Criteria:

• allergy to allopurinol
• current treatment with allopurinol
• Gout

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; pills exactly as the drug will be delivered to participants. Instructions will be made to take the pill once a day.	Drug: Allopurinol; Allopurinol 100 to 300 mg a day for 3 months
Active Comparator: Allopurinol; pills exactly as the placebo will be delivered to participants. Instructions will be made to take the pill once a day.	Drug: Allopurinol; Allopurinol 100 to 300 mg a day for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1,25 dihydroxivitamin D	Increase in 1,25 dihydroxivitamin D	3 months
FGF-23	Reduction of FGF-23	3 months
Klotho	Increase in alpha Klotho	3 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Estimated): December 30, 2023
• Study Completion (Estimated): April 30, 2024

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: October 26, 2022
• First Posted (Actual): November 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 29, 2023
• Last Update Submitted That Met QC Criteria: August 28, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: chronic kidney disease; vitamin D; allopurinol; mineral and bone metabolism; uric acid
• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Allopurinol
• Other Study ID Numbers: Alopurinol-CKD-MBD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No