Negri AL, Spivacow FR. Kidney stone matrix proteins: Role in stone formation. World J Nephrol 2023; 12(2): 21-28 [PMID: 37035509 DOI: 10.5527/wjn.v12.i2.21]
Corresponding Author of This Article
Armando Luis Negri, FACP, MD, Academic Editor, Professor, Department of Physiology and Biophysics, Universidad del Salvador, Instituto de Investigaciones Metabólicas, Libertad 836 1 Piso, Buenos Aires 1012, Argentina. negri@casasco.com.ar
Research Domain of This Article
Urology & Nephrology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Nephrol. Mar 25, 2023; 12(2): 21-28 Published online Mar 25, 2023. doi: 10.5527/wjn.v12.i2.21
Kidney stone matrix proteins: Role in stone formation
Armando Luis Negri, Francisco Rodolfo Spivacow
Armando Luis Negri, Department of Physiology and Biophysics, Universidad del Salvador, Instituto de Investigaciones Metabólicas, Buenos Aires 1012, Argentina
Francisco Rodolfo Spivacow, Department of Nephrology, Instituto de Investigaciones Metabólicas, Buenos Aires 1012, Argentina
Author contributions: Negri AL and Spivacow FR performed article design, literature review, and manuscript writing and final edition; Negri AL and Spivacow FR contributed equally to this work.
Conflict-of-interest statement: Both authors declare no conflict of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Armando Luis Negri, FACP, MD, Academic Editor, Professor, Department of Physiology and Biophysics, Universidad del Salvador, Instituto de Investigaciones Metabólicas, Libertad 836 1 Piso, Buenos Aires 1012, Argentina. negri@casasco.com.ar
Received: October 18, 2022 Peer-review started: October 18, 2022 First decision: December 26, 2022 Revised: January 18, 2023 Accepted: March 17, 2023 Article in press: March 17, 2023 Published online: March 25, 2023
Abstract
Stone formation is induced by an increased level of urine crystallization promoters and reduced levels of its inhibitors. Crystallization inhibitors include citrate, magnesium, zinc, and organic compounds such as glycosaminoglycans. In the urine, there are various proteins, such as uromodulin (Tamm-Horsfall protein), calgranulin, osteopontin, bikunin, and nephrocalcin, that are present in the stone matrix. The presence of several carboxyl groups in these macromolecules reduces calcium oxalate monohydrate crystal adhesion to the urinary epithelium and could potentially protect against lithiasis. Proteins are the most abundant component of kidney stone matrix, and their presence may reflect the process of stone formation. Many recent studies have explored the proteomics of urinary stones. Among the stone matrix proteins, the most frequently identified were uromodulin, S100 proteins (calgranulins A and B), osteopontin, and several other proteins typically engaged in inflammation and immune response. The normal level and structure of these macromolecules may constitute protection against calcium salt formation. Paradoxically, most of them may act as both promoters and inhibitors depending on circumstances. Many of these proteins have other functions in modulating oxidative stress, immune function, and inflammation that could also influence stone formation. Yet, the role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.
Core Tip: Several urinary proteins have been found in kidney stone matrix. In vitro and in vivo studies have shown that they have an important role in various processes of calcium oxalate crystallization. Many of them have other functions in modulating oxidative stress, immune response, and inflammation that could also influence stone formation. Yet, the exact role of these kidney stone matrix proteins needs to be established through more studies comparing urinary stone proteomics between stone formers and non-stone formers.
