Effect of Allopurinol on Markers of Mineral and Bone Metabolism

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Chronic Kidney Diseases, Osteodystrophy, Uric Acid Concentration, Serum, Quantitative Trait Locus 7

Intervention / Treatment
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* Drug: Allopurinol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: stage 3, 4 or 5 CKD on conservative management - Exclusion Criteria: allergy to allopurinol current treatment with allopurinol Gout

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, allopurinol, mineral and bone metabolism, uric acid, vitamin D