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World J Clin Pediatr. Jan 9, 2022; 11(1): 14-26
Published online Jan 9, 2022. doi: 10.5409/wjcp.v11.i1.14
Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement
Osama Y Safdar, Rana M Baghdadi, Sereen A Alahmadi, Bana E Fakieh, Amaal M Algaydi
Osama Y Safdar, Department of Pediatric, King Abdulaziz University, JEDDAH 21414, Saudi Arabia
Rana M Baghdadi, Sereen A Alahmadi, Bana E Fakieh, Amaal M Algaydi, College of Medicine, King Abdulaziz University, JEDDAH 21422, Saudi Arabia
Author contributions: Baghdadi RM formulated the idea; Baghdadi RM, Alahmadi SA, Algaydi AM, and Fakieh BE investigated and extracted data; Baghdadi RM, Alahmadi SA, Algaydi AM, and Fakieh BE wrote and prepared the original draft; Baghdadi RM, Alahmadi SA, and Fakieh BE reviewed and edited; Safdar OY supervised; all authors have read and agreed to the published version of the manuscript; all authors have contributed substantially to this paper.
Conflict-of-interest statement: The authors declare no conflict of interests 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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Osama Y Safdar, MD, Associate Professor, Pediatric Nephrology Center of Excellence, Department of Pediatric, King Abdulaziz University, 15 Altahlia, Jeddah, JEDDAH 21414, Saudi Arabia. ssafdar@kau.edu.sa
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: July 30, 2021
Revised: August 12, 2021
Accepted: November 15, 2021
Article in press: November 15, 2021
Published online: January 9, 2022
Processing time: 312 Days and 23 Hours
Abstract

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.

Keywords: Sickle cell disease, Sickle cell nephropathy, Chronic kidney disease, Kidney injury molecule-1, Monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase

Core Tip: This study discusses the expected clinical and biochemical progression among patients with sickle cell nephropathy, the utility of various biomarkers, and the limitations of conventional biomarkers. Novel biomarkers used in combination have been demonstrated to have a higher diagnostic yield as compared to that of individual markers, necessitating a collaborative approach in the standardization and utilization of promising biomarkers such as kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, cation channels, and endothelial dysfunction.