Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies

Study Overview
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Brief Summary
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The aim of this study is to assess the serum uric-acid lowering effect of losartan in children with proteinuric nephropathies. Patients already treated with enalapril will be randomized to receive losartan and/or enalapril in a cross-over designed study. Those who recruit the inclusion criteria will receive enalapril and/or losartan during a one month period, followed by a 15 days of wash out (under enalapril treatment). On day 46, the second period of 30 days of treatment start (enalapril or losartan, whichever was not received initially). Before randomization, a baseline 24 hours urine and a fasting blood sample will be obtained to assess uric acid excretion and serum uric acid values along with renal function and electrolyte levels. Then, similar determinations will be performed at days 30, 46 and 76.

Detailed Description
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The working hypothesis is that the administration to losartan reduces significantly the serum uric acid levels in normotensive children with proteinuric nephropathies. The study will consist in a single center cross-over randomized, open label, clinical trial. Inclusion criteria will be:children with poteinuric nephropathies already treated with enalapril under our care, age between 3 and 12 years and normal blood pressure. Subjects will be selected by simple probability sampling and after the signature of the assent/informed consent, they will be randomized (blocks of 4 patients, treatment sequence 2:2) to receive a two phases regime of drugs: 1) arm enalapril-losartan, or 2) arm losartan-enalapril. Between phases there will be a 14 days wash out period (during this time patients will continue receiving enalapril, as this drug does not have effect on uric acid metabolism). The dose of enalapril will be that they usually receive, while the dose of losartan will be 5 times the those of enalapril that they usually receive. Visit Schedule: day 1 (randomization) and 30 for the first drug; 15 days wash out period, day 46 and 76 for the second drug. In each visit a physical examination and blood pressure monitor will be performed, along with the following laboratory parameters: urea, creatinine, electrolytes, uric acid, glycemia, triglycerides, cholesterol and lipopolysaccharides. Simultaneously, in a spot urine morning sample will be determined the levels of uric acid, creatinine, proteinuria y albuminuria.

Official Title
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Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies: a Cross-over Randomized Clinical Trail

Conditions
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Uric Acid Nephropathy

Intervention / Treatment
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* Drug: Losartan Potassium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children with poteinuric nephropathies already treated with enalapril under our care. Age between 3 and 12 years. Normal blood pressure. Exclusion Criteria: Patients with high blood pressure. Post menarche female patients. Patients with hypouricemia (< 2 mg/dL). Patients treated with diuretics. Patients with absolute or relative contraindications to receive RAAS antagonists (glomerular filtration < 30 ml/min/1,73 m2, serum potassium > 5,5 mEq/L). Patients with active rheumatic diseases. Patients treated with dual blockade of the RAAS (enalapril +losartan). Patients treated with calcineurin inhibitors.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 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: Crossover Assignment
Interventional Model Description: Patients already treated with enalapril will be randomized to receive losartan or enalapril in a cross-over designed study. Those who recruit the inclusion criteria will receive enalapril and/or losartan during a one month period, followed by a 15 days of wash out (under enalapril treatment). On day 46, the second period of 30 days of treatment starts (enalapril or losartan, whichever was not received initially).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enalapril<br>Children with proteinuric nephropathies will receive enalapril prior or after a losartan period, according to randomization sequence. Enalapril will be given at a dose between 0.1 to 0.4 mg/kg/day (according to the dose that they usually receive), once a day. | Drug: Losartan Potassium<br>* Patients will receive losartan potassium for 30 days.<br>|
| Experimental: Losartan<br>Children with proteinuric nephropathies will receive losartan prior or after a enalapril period, according to randomization sequence. Losartan will be given at a dose 5 times the dose of enalapril that they usually receive, (with a maximum dose of 1.4 mg/kg/day), once a day. | Drug: Losartan Potassium<br>* Patients will receive losartan potassium for 30 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum uric acid levels after losartan treatment | Patiens will receive a losartan regime after serum uric acid levels will be assessed | 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary uric acid levels after losartan treatment | Patiens will receive a losartan regime after urinary uric acid levels will be assessed | 30 days |