Losartan and Uric Acid Metabolism in Children With Proteinuric Nephropathies

NCT ID: NCT05402397

Last Updated: 2025-09-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-01

Study Completion Date

2024-01-01

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.

Conditions

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Uric Acid Nephropathy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Enalapril

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.

Group Type ACTIVE_COMPARATOR

Losartan Potassium

Intervention Type DRUG

Patients will receive losartan potassium for 30 days.

Losartan

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.

Group Type EXPERIMENTAL

Losartan Potassium

Intervention Type DRUG

Patients will receive losartan potassium for 30 days.

Interventions

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Losartan Potassium

Patients will receive losartan potassium for 30 days.

Intervention Type DRUG

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.
Minimum Eligible Age

3 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hospital General de Niños Pedro de Elizalde

OTHER

Sponsor Role lead

Responsible Party

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Alejandro Balestracci

Staff Nephrology Unit Hospital General de Niños Pedro de Elizalde

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Alejandro Balestracci, MD, Ph. D.

Role: PRINCIPAL_INVESTIGATOR

Hospital General de Niños Pedro de Elizalde

Locations

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HGNPE

CABA, Buenos Aires F.D., Argentina

Site Status

Countries

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Argentina

References

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Park JH, Jo YI, Lee JH. Renal effects of uric acid: hyperuricemia and hypouricemia. Korean J Intern Med. 2020 Nov;35(6):1291-1304. doi: 10.3904/kjim.2020.410. Epub 2020 Sep 9.

Reference Type BACKGROUND
PMID: 32872730 (View on PubMed)

Wuhl E, Schaefer F. Therapeutic strategies to slow chronic kidney disease progression. Pediatr Nephrol. 2008 May;23(5):705-16. doi: 10.1007/s00467-008-0789-y. Epub 2008 Mar 12.

Reference Type BACKGROUND
PMID: 18335252 (View on PubMed)

Weaver DJ Jr. Uric acid and progression of chronic kidney disease. Pediatr Nephrol. 2019 May;34(5):801-809. doi: 10.1007/s00467-018-3979-2. Epub 2018 Jun 21.

Reference Type BACKGROUND
PMID: 29931555 (View on PubMed)

Sutton Burke EM, Kelly TC, Shoales LA, Nagel AK. Angiotensin Receptor Blockers Effect on Serum Uric Acid-A Class Effect? J Pharm Pract. 2020 Dec;33(6):874-881. doi: 10.1177/0897190019866315. Epub 2019 Aug 7.

Reference Type BACKGROUND
PMID: 31390929 (View on PubMed)

Bryant CE, Rajai A, Webb NJA, Hogg RJ. Effects of losartan and enalapril on serum uric acid and GFR in children with proteinuria. Pediatr Nephrol. 2021 Oct;36(10):3211-3219. doi: 10.1007/s00467-021-05045-4. Epub 2021 Apr 21.

Reference Type BACKGROUND
PMID: 33881639 (View on PubMed)

Hamada T, Ichida K, Hosoyamada M, Mizuta E, Yanagihara K, Sonoyama K, Sugihara S, Igawa O, Hosoya T, Ohtahara A, Shigamasa C, Yamamoto Y, Ninomiya H, Hisatome I. Uricosuric action of losartan via the inhibition of urate transporter 1 (URAT 1) in hypertensive patients. Am J Hypertens. 2008 Oct;21(10):1157-62. doi: 10.1038/ajh.2008.245. Epub 2008 Jul 31.

Reference Type BACKGROUND
PMID: 18670416 (View on PubMed)

Kubota M. Hyperuricemia in Children and Adolescents: Present Knowledge and Future Directions. J Nutr Metab. 2019 May 2;2019:3480718. doi: 10.1155/2019/3480718. eCollection 2019.

Reference Type BACKGROUND
PMID: 31192008 (View on PubMed)

Dang A, Zhang Y, Liu G, Chen G, Song W, Wang B. Effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia in Chinese population. J Hum Hypertens. 2006 Jan;20(1):45-50. doi: 10.1038/sj.jhh.1001941.

Reference Type BACKGROUND
PMID: 16281062 (View on PubMed)

Wurzner G, Gerster JC, Chiolero A, Maillard M, Fallab-Stubi CL, Brunner HR, Burnier M. Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. J Hypertens. 2001 Oct;19(10):1855-60. doi: 10.1097/00004872-200110000-00021.

Reference Type BACKGROUND
PMID: 11593107 (View on PubMed)

Other Identifiers

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HGNPE 7122

Identifier Type: -

Identifier Source: org_study_id

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