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Hiding in plain sight: genetics of childhood steroid-resistant nephrotic syndrome in Sub-Saharan Africa

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Abstract

Steroid-resistant nephrotic syndrome (SRNS) is the most severe form of childhood nephrotic syndrome with an increased risk of progression to chronic kidney disease stage 5. Research endeavors to date have identified more than 80 genes that are associated with SRNS. Most of these genes regulate the structure and function of the podocyte, the visceral epithelial cells of the glomerulus. Although individuals of African ancestry have the highest prevalence of SRNS, especially those from Sub-Saharan Africa (SSA), with rates as high as 30–40% of all cases of nephrotic syndrome, studies focusing on the characterization and understanding of the genetic basis of SRNS in the region are negligible compared with Europe and North America. Therefore, it remains unclear if some of the variants in SRNS genes that are deemed pathogenic for SRNS are truly disease causing, and if the leading causes of monogenic nephrotic syndrome in other populations are the same for children in SSA with SRNS. Other implications of this lack of genetic data for SRNS in the region include the exclusion of children from the region from clinical trials aimed at identifying potential novel therapeutic agents for this severe form of nephrotic syndrome. This review underlines a need for concerted efforts to advance the genetic basis of SRNS in children in SSA. Such endeavors will complement global efforts at understanding the genetic basis of nephrotic syndrome.

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Funding

This study was funded by the National Institute of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) 5R01DK098135 5R01DK094987 and the NIH Eunice Kennedy Shriver National Institute of Child Health and Human Development NICHD 1R21HD104176-01, to RAG. CIE was supported by the Fogarty International Center of the NIH D43TW010134. NHLBI R38HL143612 and the Duke Pediatric Research Scholars Program support to AEW.

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  1. Department of Pediatrics, Division of Nephrology, Duke University Medical Center, Durham, NC, 27710, USA

    Anna Elizabeth Williams, Brandon M. Lane & Rasheed A. Gbadegesin

  2. Department of Pediatrics, Faculty of Clinical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria

    Christopher I. Esezobor

  3. Duke Molecular Physiology Institute, Duke University, Durham, NC, USA

    Brandon M. Lane & Rasheed A. Gbadegesin

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  1. Anna Elizabeth Williams
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Williams, A.E., Esezobor, C.I., Lane, B.M. et al. Hiding in plain sight: genetics of childhood steroid-resistant nephrotic syndrome in Sub-Saharan Africa. Pediatr Nephrol 38, 2003–2012 (2023). https://doi.org/10.1007/s00467-022-05831-8

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