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Review
. 2023 Jul;38(7):2003-2012.
doi: 10.1007/s00467-022-05831-8. Epub 2022 Dec 2.

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

Anna Elizabeth Williams  1 , Christopher I Esezobor  2 , Brandon M Lane  1   3 , Rasheed A Gbadegesin  4   5
Affiliations
Review

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

Anna Elizabeth Williams et al. Pediatr Nephrol. 2023 Jul.

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.

Keywords: Africa; Genetic SRNS; Nephrotic syndrome; Pediatrics; SRNS.

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Conflict of interest statement

Disclosures

None of the authors in this study has conflicts of interest to disclose.

Figures

Figure 1:
Figure 1:. Genetic causes of SRNS
A) Depiction of the >80 SRNS genes identified globally and their expression in podocytes (orange) and basement membrane (blue) that constitute part of the glomerular filtration barrier. B) The limited genetic studies in SSA have identified only a few genes that contribute to SRNS in this population.
Figure 2:
Figure 2:. Monogenic SRNS reported from Sub-Saharan Africa
The geographic region described as Sub-Saharan Africa is shown in deep grey shade. Founder mutations in NPHS2 have been reported from South Africa, same variant was reported from Comoros Island.
See this image and copyright information in PMC

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