Retrospective Cohort Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Nephrol. Jul 25, 2021; 10(4): 47-58
Published online Jul 25, 2021. doi: 10.5527/wjn.v10.i4.47
Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents?
Maria Goretti Moreira Guimarães Penido, Marcelo de Sousa Tavares
Maria Goretti Moreira Guimarães Penido, Marcelo de Sousa Tavares, Pediatric Nephrology Unit, Nephrology Center of Santa Casa de Belo Horizonte, Belo Horizonte 30150320, Minas Gerais, Brazil
Maria Goretti Moreira Guimarães Penido, Federal University of Minas Gerais, Faculty of Medicine, Department of Pediatrics, Pediatric Nephrology Unit, Belo Horizonte 30130100, Minas Gerais, Brazil
Author contributions: Penido MGMG and Tavares MS contributed equally to the conception and design of the study, the acquisition, analysis and interpretation of data, and the drafting and critical revision of the final article.
Institutional review board statement: The study was approved by the institutional review board of the Clinics Hospital of the Federal University of Minas Gerais, Brazil (ETIC 0479.0.203.000-10, December 01, 2010) and by the Research Ethics Committee of Santa Casa de Belo Horizonte. It was conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at: mariagorettipenido@yahoo.com.br. Participants gave informed consent for data sharing. Data are anonymized and there were no risk of identification.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria Goretti Moreira Guimarães Penido, FRCP (Hon), MD, PhD, Associate Professor, Chief Doctor, Professor, Pediatric Nephrology Unit, Nephrology Center of Santa Casa de Belo Horizonte, Rua Piauí 420, Santa Efigênia, Belo Horizonte 30150320, Minas Gerais, Brazil. mariagorettipenido@yahoo.com.br
Received: March 30, 2021
Peer-review started: April 1, 2021
First decision: July 8, 2021
Revised: July 18, 2021
Accepted: July 22, 2021
Article in press: July 22, 2021
Published online: July 25, 2021
Processing time: 129 Days and 3.2 Hours
Abstract
BACKGROUND

Hypercalciuria is the most common metabolic risk factor for calcium urolithiasis and is associated with bone loss in adult patients. Reduced bone mineral density (BMD) was already described in idiopathic hypercalciuria (IH) children, but the precise mechanisms of bone loss or inadequate bone mass gain remain unknown. Life-long hypercalciuria might be considered a risk to change bone structure and determine low bone mass throughout life. The peak of bone mass should occur without interferences. A beneficial effect of citrate formulations and thiazides on bone mass in adult and pediatric patients with IH have been shown.

AIM

To evaluate whether pharmacological therapy has a beneficial effect on bone mass in children and adolescents with IH.

METHODS

This retrospective cohort study evaluated 40 hypercalciuric children non-responsive to lifestyle and diet changes. After a 2-mo run-in period of citrate formulation (Kcitrate) usage, the first bone densitometry (DXA) was ordered. In patients with sustained hypercalciuria, a thiazide diuretic was prescribed. The second DXA was performed after 12 mo. Bone densitometry was performed by DXA at lumbar spine (L2-L4). A 24-h urine (calcium, citrate, creatinine) and blood samples (urea, creatinine, uric acid, calcium, phosphorus, magnesium, chloride, hemoglobin) were obtained. Clinical data included age, gender, weight, height and body mass index.

RESULTS

Forty IH children; median age 10.5 year and median time follow-up 6.0 year were evaluated. Nine patients were treated with Kcitrate (G1) and 31 with Kcitrate + thiazide (G2). There were no differences in age, gender, body mass index z-score and biochemical parameters between G1 and G2. There were no increases in total cholesterol, kalemia and magnesemia. Calciuria decreased in both groups after treatment. Lumbar spine BMD z-score increased after thiazide treatment in G2. There was no improvement in G1.

CONCLUSION

Results point to a beneficial effect of thiazide on lumbar spine BMD z-score in children with IH. Further studies are necessary to confirm the results of the present study.

Keywords: Children; Adolescent; Hypercalciuria; Bone mineral density; Thiazides; Citrate

Core Tip: Should pediatric idiopathic hypercalciuria be treated with hypocalciuric agents? Reduction in bone mass has already been described in hypercalciuric pediatric patients, and the precise mechanisms of bone loss or failure to achieve adequate bone mass remain unknown. Initial recommendations for the treatment of hypercalciuric pediatric patients consist of lifestyle changes and adequate diet. Children rarely comply with those recommendations and require potassium citrate supplementation or thiazides to reduce calciuria. However, anticalciuric therapy in children and adolescents is not based on strong clinical evidences. We speculate if the anticalciuric effect of pharmacologic therapy has a beneficial role on bone mass in pediatric idiopathic hypercalciuria and compromised bone mass in adulthood.